A Phase 2 Clinical Trial Evaluating the Efficacy and Safety of Dual Immune Checkpoint Inhibition With Anti-PD-L1 (Atezolizumab) and Anti-TIGIT (Tiragolumab) in Cancer of Unknown Primary

The goal of this clinical research study is to learn if the combination of atezolizumab and tiragolumab can help to control cancers of unknown primary. The safety and effects of this drug combination will also be studied

Start Date30 Jun 2025

Sponsor / Collaborator

Genentech, Inc.

NCT06760481

/ Not yet recruitingPhase 1IIT

Phase I/Ib Trial of TIraGolumab, AtEzolizumab, and RadScopal Radiation in Patients With Advanced Solid Malignancies (TIGER)

An open-label, Phase I/Ib study investigating the safety and efficacy of tiragolumab + atezolizumab + RadScopal™ XRT in patients with metastatic solid malignancies.

Start Date30 Jun 2025

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

NCT06784947

/ RecruitingPhase 2IIT

A Phase II Trial of Tiragolumab in Combination with Atezolizumab and Bevacizumab in Patients with Previously Treated, Microsatellite Stable, Metastatic Colorectal Adenocarcinoma

The goal of this study is to learn if a new combination treatment is effective for patients with microsatellite stable, advanced colorectal cancer. The study treatment combines 3 drugs: atezolizumab, bevacizumab, and tiragolumab. The main questions the study aims to answer are:
1. Does the study treatment effectively treat colorectal cancer?
2. Is the study treatment safe for patients with colorectal cancer?
3. How does the study treatment effect the immune system in patients with colorectal cancer?
Participants in this study will receive the study treatment and undergo checkups, laboratory tests, and imaging tests for monitoring. Some participants will also undergo tumor biopsies.

Start Date01 May 2025

Sponsor / Collaborator

University of Colorado Denver

[+1]

100 Clinical Results associated with Tiragolumab

100 Translational Medicine associated with Tiragolumab

100 Patents (Medical) associated with Tiragolumab

Literatures (Medical) associated with Tiragolumab

01 Feb 2025·LANCET ONCOLOGY

Tiragolumab in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (MORPHEUS-Liver): a randomised, open-label, phase 1b–2, study

Article

Author: Yu, Nancy ; Wang, Yulei ; Hack, Stephen P ; Mahrus, Sami ; Ryoo, Baek-Yeol ; Burgoyne, Adam M ; Secrest, Matthew H ; Li, Daneng ; Yin, Anqi ; Edubilli, Tirupathi Rao ; Finn, Richard S ; Gane, Ed ; Cotter, Christopher ; Badhrinarayanan, Shreya ; Shemesh, Colby S ; Cha, Edward ; Hsu, Chih-Hung

BACKGROUND:

PD-L1 and VEGF blockade with atezolizumab plus bevacizumab has been shown to improve survival in unresectable hepatocellular carcinoma. TIGIT is an immune checkpoint regulator implicated in many cancers, including unresectable hepatocellular carcinoma. Here, we evaluate the clinical activity and safety of the addition of tiragolumab, an anti-TIGIT monoclonal antibody, to atezolizumab plus bevacizumab.

METHODS:

This randomised, open-label, phase 1b-2 umbrella study was conducted at 26 centres across China, France, Israel, New Zealand, South Korea, Taiwan, and the USA. Eligible patients were adults aged 18 years old or older with previously untreated locally advanced unresectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0-1, Child-Pugh class A disease, and a life expectancy of at least 3 months. Eligible patients were randomly assigned (2:1) using permuted block randomisation to receive either tiragolumab 600 mg plus atezolizumab 1200 mg plus bevacizumab 15 mg/kg or atezolizumab 1200 mg plus bevacizumab 15 mg/kg, administered via intravenous infusion every 3 weeks on day 1 of each 21-day cycle. Patients received treatment until unacceptable toxic effects or loss of clinical benefit, whichever occurred first. The primary endpoint was objective response rate. Analysis of clinical activity was done in the efficacy-evaluable population (all patients who received at least one dose of each drug for their assigned treatment regimen) and safety was assessed in all patients who received any study treatment. The trial is registered with ClinicalTrials.gov, NCT04524871, and is ongoing.

FINDINGS:

Between Aug 20, 2020, and Feb 10, 2022, we assessed 154 patients for eligibility and 59 eligible patients were randomly assigned to receive tiragolumab plus atezolizumab plus bevacizumab (n=41) or atezolizumab plus bevacizumab (n=18); one patient in the tiragolumab plus atezolizumab plus bevacizumab group experienced an adverse event before receiving any treatment and withdrew from the study. Median age was 65·0 years (IQR 61·0-73·0). 46 (79%) of 58 patients were male and 12 (21%) were female. Most patients were Asian (23 [40%]) or White (21 [36%]). At the time of clinical cutoff (Aug 21, 2023), median follow-up was 20·6 months (IQR 10·6-28·0) in the tiragolumab plus atezolizumab plus bevacizumab group and 14·0 months (4·2-18·5) in the atezolizumab plus bevacizumab group. The confirmed objective response rate was 43% (95% CI 27-59, n=17) in the tiragolumab plus atezolizumab plus bevacizumab group and 11% (1-35, n=2) in the atezolizumab plus bevacizumab group. All patients in both groups experienced an adverse event. The incidence of pruritis (20 [50%] of 40 patients vs three [17%] of 18 patients), arthralgia (13 [33%] vs two [11%]), and diarrhoea (12 [30%] vs one [6%]) was notably higher in the tiragolumab plus atezolizumab plus bevacizumab group than in the atezolizumab plus bevacizumab group, although these were mainly grade 1-2. The most common grade 3-4 adverse events were hypertension (six [15%] of 40 patients in the tiragolumab plus atezolizumab plus bevacizumab group vs two [11%] of 18 patients in the atezolizumab plus bevacizumab group), aspartate aminotransferase increased (three [8%] of 40 patients vs one [6%] of 18 patients), and proteinuria (two [5%] of 40 patients vs two [11%] of 18 patients). Serious adverse events occurred in 21 (53%) of 40 patients in the tiragolumab plus atezolizumab plus bevacizumab group and in ten (56%) of 18 patients in the atezolizumab plus bevacizumab group. Treatment-related deaths occurred in one patient in the tiragolumab plus atezolizumab plus bevacizumab group (due to cholestasis) and two patients in the atezolizumab plus bevacizumab group (due to oesophageal varices haemorrhage and upper gastrointestinal haemorrhage). The addition of tiragolumab to atezolizumab plus bevacizumab did not appear to result in a substantial worsening of treatment-related or immune-mediated adverse events, and no new safety signals were identified.

INTERPRETATION:

This signal-seeking study suggests that the addition of tiragolumab to atezolizumab and bevacizumab might be more clinically active than atezolizumab plus bevacizumab alone in unresectable hepatocellular carcinoma. Based on these data, further study of combination tiragolumab plus atezolizumab plus bevacizumab is warranted.

FUNDING:

F Hoffmann-La Roche and Genentech.

01 Jan 2025·European Journal of Nuclear Medicine and Molecular Imaging

Development and characterisation of [18F]TTDP, a novel T cell immunoglobulin and ITIM domain tracer, in humanised mice and non-human primates

Article

Author: Zhao, Fangyu ; Wang, Tianyi ; Yu, Hong ; Zhu, Mengyuan ; Li, Xinyu ; Wu, Yongyi ; Guan, Zhengqi ; Han, Zhaoguo ; Wang, Yueqi ; Sun, Ying ; Li, Xiaoqian ; Hu, Xinxin ; Wang, Hongbin ; Sun, Xilin ; Zhang, Duoyi ; A, Rong ; Wang, Jiannan ; Chen, Wei ; Wang, Jing ; Li, Xiaona ; Liu, Yang

PURPOSE:

The T cell immunoglobulin and ITIM domain (TIGIT) blockade immunotherapy response is directly associated with individual differences of TIGIT expression on tumour-infiltrating lymphocytes (TILs) in tumour immune microenvironment (TIME) of non-small cell lung cancer (NSCLC). Here, we developed a TIGIT-targeted PET tracer to evaluate its feasibility in predicting immunotherapy efficacy, aiming to manage NSCLC patients accurately.

METHODS:

We synthesised a ¹⁸F-labeled TIGIT-targeted D-peptide, [¹⁸F]TTDP, and investigated the specificity of [¹⁸F]TTDP both to murine TIGIT and human TIGIT by a series of in vitro and in vivo assays. [¹⁸F]TTDP PET imaging was performed in humanised immune system (HIS) mice models bearing NSCLC patient-derived xenografts (PDXs) to evaluate the predictive value of FDA-approved combination immunotherapy of atezolizumab plus tiragolumab. Lastly, rhesus macaque was applied for [¹⁸F] TTDP PET to explore the tracer's in vivo distribution and translational potential in non-human primates.

RESULTS:

[¹⁸F]TTDP showed high specificity for both murine TIGIT and human TIGIT in vitro and in vivo. The HIS NSCLC PDX platform was successfully established for [¹⁸F]TTDP PET imaging, and tumour uptake of [¹⁸F]TTDP was significantly correlated with the TIGIT expression of TILs in the TIME. [¹⁸F]TTDP PET imaging, in predicting treatment response to the combination immunotherapy in NSCLC HIS-PDX models, showed a sensitivity of 83.33% and a specificity of 100%. In addition, [¹⁸F]TTDP PET also showed cross-species consistency of the tracer biodistribution between non-human primate and murine animals, and no adverse events were observed.

CONCLUSION:

The combined implementation of the [¹⁸F]TTDP and HIS-PDX model creates a state-of-the-art preclinical platform that will impact the identification and validation of TIGIT-targeted PET image-guided diagnosis, treatment response prediction, beneficial patient screening, novel immunotherapies, and ultimately the outcome of NSCLC patients. We first provided in vivo biodistribution of [¹⁸F]TTDP PET imaging in rhesus macaque, indicating its excellent translational potential in the clinic.

04 Sep 2024·Future Oncology

IMbrave152/SKYSCRAPER-14: a Phase III study of atezolizumab, bevacizumab and tiragolumab in advanced hepatocellular carcinoma

Article

Author: Li, Daneng ; Lin, Ya-Chen ; Cotter, Christopher ; Kudo, Masatoshi ; Zhu, Huaqi ; Badhrinarayanan, Shreya

Atezolizumab plus bevacizumab is a standard of care, first-line therapy for advanced hepatocellular carcinoma (HCC). Myeloid and T regulatory cells are key immunosuppressive cell types within the hepatic tumor microenvironment associated with clinical resistance to atezolizumab and bevacizumab therapy for HCC and overall poor prognosis. Therapeutic targeting of TIGIT, which is highly expressed in these cells, with tiragolumab may overcome the immunosuppressive environment and improve clinical benefit, a hypothesis supported by positive efficacy signals in the Phase Ib/II MORPHEUS-Liver study. This paper describes the rationale and design of IMbrave152/SKYSCRAPER-14, a randomized, double-blind, placebo-controlled Phase III study comparing atezolizumab and bevacizumab with tiragolumab or placebo in patients with HCC and no prior systemic treatment.Clinical Trial Registration: NCT05904886 (ClinicalTrials.gov).

122

News (Medical) associated with Tiragolumab

06 Mar 2025

·www.prnewswire.com

TEPMETKO Continues to Strengthens its Position as a Leading METex14 Skipping NSCLC Therapy | DelveInsight

With increasing biomarker-driven cancer treatments, TEPMETKO benefits from growing adoption in precision oncology. Competition from other MET inhibitors like TABRECTA (capmatinib) exists, but TEPMETKO's once-daily dosing and efficacy profile offer differentiation. LAS VEGAS, March 6, 2025 /PRNewswire/ -- DelveInsight's " TEPMETKO Market Size, Forecast, and Market Insight Report" highlights the details around TEPMETKO, a kinase inhibitor indicated for the treatment of adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of TEPMETKO. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. EMD Serono's TEPMETKO (tepotinib) Overview TEPMETKO is a kinase inhibitor prescribed for adult patients with metastatic non-small cell lung cancer (NSCLC) carrying MET exon 14 skipping alterations. The active component is Tepotinib (as hydrochloride monohydrate), administered orally. Patients should be cautioned about the heightened risk of severe or fatal interstitial lung disease/pneumonitis, liver toxicity, and potential embryo-fetal toxicity, necessitating effective contraception during and shortly after treatment. Tepotinib specifically targets MET, including variants with exon 14 skipping mutations. It blocks HGF-dependent and independent MET phosphorylation, disrupting MET-driven signaling pathways. Additionally, at clinically relevant concentrations, Tepotinib inhibits melatonin 2 and imidazoline 1 receptors. In vitro studies show that it suppresses tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent cancer cells. In mouse models with MET-driven tumors, including those with MET exon 14 skipping alterations, Tepotinib reduced tumor growth, sustained MET phosphorylation inhibition, and, in one case, decreased metastasis formation. The recommended dose of TEPMETKO is 450 mg taken orally once daily until disease progression or intolerable toxicity occurs. Patients should take it at the same time each day, swallowing tablets whole without chewing, crushing, or splitting them. If a dose is missed and less than eight hours remain until the next scheduled dose, patients should skip it. In cases of vomiting after taking TEPMETKO, the next dose should be taken at the usual time. Learn more about TEPMETKO projected market size for NSCLC @ TEPMETKO Market Potential Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 81% of all diagnosed cases. Early detection greatly improves outcomes, but diagnosing NSCLC and other lung cancers is challenging because their symptoms are often mistaken for common illnesses or the long-term effects of smoking. Consequently, 80% of NSCLC cases are already at advanced stages by the time they are identified, making treatment more difficult. Around 80% of EGFR mutations in NSCLC involve either exon 19 deletions or the exon 21 L858R substitution, both of which are classified as sensitizing mutations. Until the last decade, chemotherapy was the primary treatment for advanced and metastatic lung cancer. However, this changed in 2015 with the approval of the first immune checkpoint inhibitor (ICI), KEYTRUDA (pembrolizumab), as a second-line therapy for advanced cases. This was followed by TECENTRIQ (atezolizumab) in 2016. Both therapies were later approved for first-line treatment, broadening their use to a larger patient population. In 2020, the combination of OPDIVO (nivolumab) and ipilimumab also received approval as a first-line treatment for metastatic NSCLC. According to DelveInsight, the NSCLC market size across the 7MM is projected to grow from USD 30 billion in 2024, with a substantial CAGR through 2034. This growth is largely driven by the introduction of emerging therapies during the forecast period (2025–2034). Discover more about the NSCLC market in detail @ Non-small Cell Lung Cancer Market Report Emerging Competitors of TEPMETKO The NSCLC pipeline is very robust with the promising therapies such as Telisotuzumab vedotin (AbbVie), Patritumab deruxtecan (Daiichi Sankyo/AstraZeneca), Datopotamab deruxtecan (Daiichi Sankyo/AstraZeneca), Eftilagimod alpha (Immutep), BNT311/GEN1046 (acasunlimab) (Genmab), V940 (mRNA-4157) + Pembrolizumab (Moderna Therapeutics/Merck), Plinabulin + Docetaxel (BeyondSpring), Olomorasib (LY3537982) (Eli Lilly and Company), Zipalertinib (Cullinan Oncology/Taiho Pharma), Ceralasertib (AZD6738) (AstraZeneca), TEDOPI (EP-2101; IDM 2101; OSE-2101) (OSE Immuno-therapeutics), Sigvotatug vedotin (PF08046047) (Pfizer), ANKTIVA (N-803) (ImmunityBio), Aumolertinib/Almonertinib/HS-10206 (Jiangsu Hansoh Pharmaceutical), Niraparib (GSK), Savolitinib (AstraZeneca/Hutchison MediPharma), TRODELVY (Gilead Sciences), Pyrotinib (Jiangsu HengRui Medicine), Ociperlimab (BGB-A1217) (BieGene), Volrustomig (AstraZeneca), Gotistobart (BNT316/ONC-392) (OncoC4/BioNTech), Ivonescimab (AK112/SMT112) (Akeso Biopharma/Summit Therapeutics), ZYNYZ (retifanlimab/INCMGA00012) (Incyte/Macrogenics), Divarasib (GDC-6036) (Roche/Genentech), Tiragolumab (RG6058) (Roche), Sacituzumab Tirumotecan (Merck and Kelun-Biotech), JEMPERLI (dostarlimab/TSR-042) (GSK and AnaptysBio), Zongertinib (BI-1810631) (Boehringer Ingelheim), BAY 2927088 (Bayer), Serplulimab (HLX10) (Shanghai Henlius Biotech), Rilvegostomig (AZD2936) (AstraZeneca), MK-1084 (Merck, Taiho Pharmaceutical, and Astex), Domvanalimab (Arcus Biosciences and Gilead Sciences), OPDUALAG (nivolumab and relatlimab) (Bristol-Myers Squibb), Belrestotug + JEMPERLI (iTeos Therapeutics and GSK), Firmonertinib (ArriVent BioPharma), Sunvozertinib (DZD9008) (Dizal Pharmaceutical), Cobolimab (GSK), Livmoniplimab (AbbVie), Fianlimab (REGN3767) (Regeneron Pharmaceuticals), BNT327/PM8002 (Biotheus/BioNTech), HS-20117 (Hansoh BioMedical), IO102-IO103 + Pembrolizumab (IO Biotech), Naptumomab estafenatox (NeoTX Therapeutics/Active Biotech), FF-10832 (FUJIFILM Corporation), BNT116 (BioNTechSE/Regeneron Pharmaceuticals), CAN-2409 (Candel Therapeutics), Mecbotamab Vedotin (BA3011/CAB-AXL-ADC) (BioAtla), Bemcentinib (BGB 324/BGB-3234/R-428) (BerGenBio/Rigel Pharmaceuticals), DOVBLERON (taletrectinib/AB-106/IBI-344) (Nuvation Bio/Innovent Biologics/Daiichi Sankyo/Nippon Kayaku), Lifileucel (Iovance Biotherapeutics), IBI363 (Innovent Biologics), Sotevtamab (AB-16B5) (Alethia Biotherapeutics), Avutometinib (VS6766) (Verastem Oncology), Vebreltinib (APL-101) (Apollomics), LP-300 (Lantern Pharma), JNJ-90301900 (Johnson & Johnson Innovative Medicine), AMG 193 (Amgen), Luveltamab tazevibulin (Sutro Biopharma), PRT3789 (Prelude Therapeutics), Disitamab vedotin (Seagen), PADCEV (enfortumab vedotin) (Astellas Pharma), RP1 (Replimune), TIVDAK (tisotumab vedotin) (Seagen), Zanidatamab (Jazz Pharmaceuticals), Utidelone injectable (UTD1) (Beijing Biostar Pharmaceuticals), REGN5093-M114 (Regeneron Pharmaceuticals), SLC-391 (SignalChem Lifesciences), fulzerasib (GenFleet), Davutamig (REGN5093) (Regeneron Pharmaceuticals), TAS3351 (Taiho Oncology), H002 (RedCloud Bio), JIN-A02 (J INTS BIO), FWD1509 (Forward Pharma), Sabestomig (AZD7789) (AstraZeneca), Sasanlimab (Pfizer), Selvigaltin (GB1211) (Galecto Biotech), Vepafestinib Helsinn (Healthcare/Taiho Pharmaceutical), EP0031 (A400/ KL590586) (Ellipses Pharma/Kelun-Biotech), Pamvatamig (MCLA-129) (Merus), Zidesamtinib (NVL-520) (Nuvalent), NVL-655 (Nuvalent), RMC-4630 (Revolution Medicines), REQORSA (quaratusugene ozeplasmid) (Genprex), PDC*lung01 (PDC*line Pharma), Evalstotug (BA3071) (BioAtla and BeiGene), PT-112 (Promontory Therapeutics), MRT-2359 (Monte Rosa Therapeutics), GAIA-102 (GAIA BioMedicine), Rigosertib (Traws Pharma), HMBD-001 (Hummingbird Bioscience), PLB1004 (Avistone Biotechnology), ANS03 (Avistone Biotechnology), MYTX-011 (Mythic Therapeutics), A166 (Sichuan Kelun-Biotech Bio-pharmaceutical), Atamparib (BN-2397) (Ribon Therapeutics), DELTACEL (KB-GDT-01) (Kiromic BioPharma), Carotuximab (ENV-105) (Kairos Pharma), YL202 (MediLink Therapeutics), and others. To know more about the number of competing drugs in development, visit @ TEPMETKO Market Positioning Compared to Other Drugs Key Milestones of TEPMETKO In February 2024, the FDA granted traditional approval to TEPMETKO for adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. In February 2022, the EC approved TEPMETKO as monotherapy for the treatment of adult patients with advanced NSCLC harboring alterations leading to METex14 skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy. In February 2021, Merck announced that the US FDA has approved TEPMETKO following priority review for the treatment of adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. This indication was approved under accelerated approval based on ORR and DOR. In October 2020, TEPMETKO received ODD for treating NSCLC with MET genomic tumor aberrations In March 2020, EMD Serono (the biopharmaceutical business of Merck KGaA), announced that the MHLW approved TEPMETKO for the treatment of patients with unresectable, advanced, or recurrent NSCLC with METex14 skipping alterations. In September 2019, the US FDA granted BTD for tepotinib in patients with metastatic NSCLC harboring METex14 skipping alterations who progressed following platinum-based cancer therapy Discover how TEPMETKO is shaping the NSCLC treatment landscape @ TEPMETKO NSCLC TEPMETKO Market Dynamics TEPMETKO competes in a growing but highly specialized market where MET-targeted therapies are gaining traction due to their efficacy in addressing MET-altered tumors. The market for MET inhibitors is expanding as precision oncology advances and molecular diagnostics become more widely available, enabling better identification of patients who would benefit from targeted treatments like TEPMETKO. A key factor shaping TEPMETKO's market dynamics is competition. It directly competes with Novartis' TABRECTA (capmatinib), another MET inhibitor approved for the same indication. While TEPMETKO offers the advantage of once-daily dosing compared to TABRECTA's twice-daily regimen, both drugs have similar efficacy profiles, making physician and patient preference an important differentiator. Additionally, broader competition from next-generation MET inhibitors and combination therapies in clinical trials could impact TEPMETKO's long-term market position. Regulatory approvals and market access play a crucial role in TEPMETKO's adoption. The drug has been approved in multiple regions, including the U.S., Europe, and Japan, but reimbursement and pricing strategies vary by market. Payer policies, along with the cost-benefit analysis of MET inhibitors compared to other targeted therapies, influence prescription trends. Furthermore, real-world evidence and post-marketing studies will be critical in demonstrating TEPMETKO's sustained effectiveness and safety, which could support expanded indications and increased market penetration. Looking ahead, the MET inhibitor market is expected to grow with advances in biomarker-driven therapy, further refining patient selection. TEPMETKO's success will depend on continued clinical development, potential label expansions, and strategic partnerships to strengthen its competitive edge. As new entrants emerge, Merck KGaA's ability to differentiate TEPMETKO through combination strategies or enhanced formulations may determine its long-term sustainability in this evolving landscape. Dive deeper to get more insight into TEPMETKO's strengths & weaknesses relative to competitors @ TEPMETKO Market Drug Report Table of Contents Related Reports Non-small Cell Lung Cancer Market Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NSCLC companies including Daiichi Sankyo, AstraZeneca, Gilead Sciences, BieGene, AbbVie, Roche, Merck, Novartis, Pfizer, Takeda Pharmaceuticals, Eli Lilly, BerGenBio, GlaxoSmithKline, Duality biologics, among others. Non-small Cell Lung Cancer Pipeline Non-small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key non-small cell lung cancer companies, including BridgeBio Pharma, Daiichi Sankyo, EMD Serono, Merck, BridgeBio Pharma, Abbvie, Pfizer, Eli Lilly and Company BioNTech SE, Shenzhen TargetRx, Taiho Pharmaceutical, Chong Kun Dang, Bristol Myers Squibb, Innovent Biologics, Xuanzhu Biopharmaceutical, Bayer, GeneScience Pharmaceuticals, InventisBio, Apollomics, Imugene, Ono Pharmaceutical, Pierre Fabre, Jiangsu Hengrui Medicine Co., Bristol-Myers Squibb, Surface Oncology, Inhibrx, Sinocelltech, Mirati Therapeutics, REVOLUTION Medicines, Yong Shun Technology Development, Iovance Biotherapeutics, Galecto Biotech, among others. C-MET Metastatic Non-small Cell Lung Cancer Market C-MET Metastatic Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key C-MET mNSCLC companies, including Novartis, Merck, EMD Serono, AbbVie, Regeneron Pharmaceuticals, Mythic Therapeutics, Apollomics, Johnson & Johnson Innovation, Haihe Biopharma, among others. C-MET Non-small Cell Lung Cancer Pipeline C-MET Non-small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key C-MET non-small cell lung cancer companies, including AbbVie, Janssen Research & Development, Beijing Pearl Biotechnology Limited Liability Company, Novartis, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug ApprovalImmunotherapyPriority Review

03 Mar 2025

·www.biospace.com

The Search for the Next Keytruda: Immuno-Oncology’s Next Play

iStock/ Bulat Silvia More than a decade after Merck’s Keytruda and BMS’ Yervoy ushered in the immuno-oncology revolution, the space is at a crossroads, with experts highlighting novel targets, combinations and pre-emptive immunization as the next wave for IO. Last year marked 10 years since Keytruda’s seminal approval . That FDA greenlight signaled a new day in immuno-oncology and set the stage for the subsequent approvals of several more checkpoint inhibitors. Now, the field is looking for its next breakthrough—but it’s been a bumpy road. Overall, the immuno-oncology (IO) space “continues to be quite disappointing,” Graig Suvannavejh, senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, told BioSpace . “Industry is in search of that next great IO target, and they just haven’t been able to identify one that works.” In the last 15 years, the FDA has approved 11 checkpoint inhibitors — therapies targeting immune checkpoint proteins, including PD-1 and its partner protein PD-L1, plus CTLA-4 and LAG-3—to help the immune system locate and attack cancer cells. While Keytruda, an anti-PD-1, gets the most credit for having kickstarted the IO revolution, it was preceded by a CTLA-4 inhibitor called Yervoy, which BMS picked up in its $2.4 billion acquisition of Medarex in 2009. Two years later, the FDA approved Yervoy as the first anti-CTLA-4 drug. “That, really, along with the anti-PD-1s, kind of ushered in this whole immuno-oncology revolution,” Suvannavejh said. Jeremy Levin, now CEO of Ovid Therapeutics who was instrumental in BMS’ transformation to an immuno-oncology company in the aughts, agreed: “It became increasingly clear that there was science that said that this whole concept of immune modulation was beginning to evolve, and that CTLA-4 was breaking open the first concepts behind it.” Lately, however, the industry appears to have hit the proverbial therapeutic wall. But it’s not for a lack of trying, according to Christiana “Chris” Bardon, co-managing partner of MPM BioImpact. “When PD-1 was first released, we spent a lot of energy as an industry looking for the next PD-1 and we must have had tens of thousands of combinations of drugs in the clinic, testing everything with PD-1,” she told BioSpace . “Basically, we were looking for the next-generation IO checkpoint inhibitor.” But despite the emergence of more therapeutic options targeting the immune system, IO treatment response rates have plateaued at around 30%, Caroline Loew, CEO of Mural Oncology, wrote in a November 2024 opinion piece for BioSpace , meaning that 70% of patients do not respond to these therapies. “Despite the incredible efficacy of PD-1,” Bardon said, there is still a huge unmet need. “We still have many cancers that don’t respond to PD-1, things that are immunologically cold.” Striking Out With TIGITs Branching out has proven difficult, however. In the IO space, Suvannavejh said anti-TIGIT checkpoint therapies have been “probably the biggest disappointment” in the past two years. In December 2021, Roche ignited the field with promising results from the Phase II CITYSCAPE study of its anti-TIGIT drug tiragolumabin in metastatic non-small cell lung cancer (NSCLC). When combined with the company’s anti-PD-L1 blocker Tecentriq, tiragolumabin reduced the risk of disease worsening or death by 38% compared to Tecentriq alone. “I think the IO space was in kind of a low place about five years ago until Roche announced positive Phase II data for their TIGIT antibody,” he said. “All of a sudden, people were like, ‘oh my god, IO is back.” But in the Phase II/III data reported last year, the tiragolumab/Tecentriq combo failed to significantly improve progression-free and overall survival versus Keytruda and chemotherapy in patients with NSCLC and Roche elected to terminate that study. The excitement fizzled after that, Suvannavejh said. It was almost the nail in the coffin for TIGITs, or at least the buzz around the drug class. Seven months earlier, in December 2023, Merck had struck out in NSCLC with its experimental anti-TIGIT antibody vibostolimab when the candidate, in combination with Keytruda, failed to hit the endpoints in a mid-stage study. Recent results have breathed new life into the space, however. In September 2024, iTeos and GSK sparked excitement with Phase II results from patients with NSCLC taking a combination of iTeos’ anti-TIGIT candidate belrestotug and GSK’s anti-PD-1 therapy Jemperli. The combo elicited a 30% better confirmed objective response rate versus Jemperli alone. The partners are now studying the regimen as a first-line therapy for NSCLC in a Phase III trial . While it remains to be seen if TIGIT-targeting checkpoint inhibitors will reach the market, Bardon noted that the industry has seen some progress with drugs that hit CTLA-4 and LAG-3. In October 2022, the FDA greenlit AstraZeneca’s anti-CTLA-4 drug Imjudo, in combination with its first-generation PD-L1 inhibitor Imfinzi, for hepatocellular carcinoma, while the LAG-3 space saw its first approval in March of that year in BMS’ relatlimab (in combination with Opdivo and marketed as Opdualag) in unresectable or metastatic melanoma. Looking ahead, Bardon said ivonescimab—a PD-1/VEGF bispecific antibody in development by Summit Therapeutics, “is really the new . . . wave of checkpoint inhibitors.” “Ivonescimab has shown superiority to PD-1 alone, which is incredible,” she said. In September, Summit presented Phase III data at the International Association for the Study of Lung Cancer’s 2024 World Conference on Lung Cancer, showing that ivonescimab outperformed Keytruda in first-line advanced NSCLC. In the HARMONi-2 trial, Summit’s candidate cut the risk of disease progression or death by nearly 50% compared with Keytruda. While the results sent Summit’s stock skyrocketing by as much as 140%, some analysts urged caution , particularly noting that the data were from a trial run only in China. “Results may or may not be generalizable beyond the China-focused patient population initially assessed,” BMO Capital Markets wrote in an investor note at the time. Summit is currently studying ivonescimab in a multi-regional Phase III NSCLC study in the U.S. Bardon added that ivonescimab has the potential to work in multiple tumor types outside of lung cancer and predicted that it would be “a huge blockbuster in the future.” Pfizer appears to agree. Last week, the New York–based pharma struck a deal with Summit to combine its vedotin-based antibody-drug conjugates with ivonescimab. Part of the reason the industry has not been successful in developing checkpoint inhibitors “is that the development path is very, very hard,” Bardon said. One key challenge, she explained, is that most checkpoint therapies do not have monotherapy efficacy and therefore need to be developed in combination with PD-1 drugs. Definitive combination therapy can only be demonstrated in a comparator trial. “It’s just a very difficult and long path to de-risk the drug.” In this way, ivonescimab benefited from being created and developed in China, where there are faster enrollment times, limited treatment options and clinical trials are less expensive, Bardon said. Other IO targets of particular interest, Suvannavejh said, are PRAME (preferentially expressed antigen of melanoma) and the “very complicated RAS pathway, which includes the commonly mutated KRAS.” “This is a pathway that people have been trying to target for decades,” Suvannavejh said. “[It is] very difficult to do, trying to get that mix of efficacy and safety.” Amgen and BMS already have KRAS drugs — Lumakras and Krazati —on the market for NSCLC. The developmental “darling” of this space, Suvannavejh said, is Revolution Medicines, whose daraxonrasib is currently in a registrational trial to treat cancers with a wide range of common RAS mutations. Other players include Eli Lilly, Immuneering Corporation and Erasca. IO Developments On the Horizon Levin indicated that the IO space is at a crossroads. “The first wave of immuno-oncology has passed us by,” he said. “We know what we know about it.” Biopharma’s appetite for IO is certainly understandable. For Merck, Keytruda brought in a cool $29.5 billion in global sales in 2024 and ranks among the best selling drugs of all time. With that drug going off patent in just a few years’ time, many companies are eager to grab more of a market that is projected to be worth more than $17 billion by 2032. So, how does biopharma catch the next wave? For Suvannavejh, the answer lies in identifying novel targets—potentially through artificial intelligence and machine learning. As an example, he offered Compugen , a Tel Aviv–based biotech that uncovered a previously unidentified checkpoint called PVRIG using its proprietary computational discovery platform. Compugen is currently studying the resulting asset, COM701 , in trials of ovarian, gastric and other cancers. “That’s what companies can do if they want to go down this path of like, hey, maybe there’s another checkpoint inhibitor that we just haven’t identified yet,” Suvannavejh said. Meanwhile, Levin said the current focus is on combination therapies. “The world teaches you this repeatedly for complex diseases,” he continued, citing childhood leukemia, hypertension and congestive heart failure as examples of where combinations have ultimately been the answer. However it’s done, Levin continued, the holy grail for IO is pre-emptively engaging the human body to defeat a cancer cell before it has even proliferated. “Immuno-oncology is the clue that you can do this,” he told BioSpace . “It says that you can absolutely galvanize the human tissue to reawaken attack on a cancer cell. The big question is, can you actually pre-emptively immunize us such that we can be ready for this?”

Clinical ResultImmunotherapyPhase 3Phase 2Drug Approval

05 Feb 2025

·www.echemi.com

Roche Reports CHF 60.5 Billion Revenue in 2024 with Focus on Oncology and R&D Adjustments

On January 30, Roche announced its financial results for 2024, reporting total revenue of CHF 60.495 billion (approximately $66.4 billion with a conversion rate of 1 CHF = 1.0981 USD), representing a 7% year-on-year growth. However, net income declined to CHF 9.187 billion (about $10.1 billion), a significant drop of 19%. The company invested CHF 13.042 billion (around $14.3 billion) in research and development, accounting for 21.6% of total revenue. Oncology continued to be the primary focus for R&D, along with substantial investments in immunology, cardiovascular, renal, and metabolic fields. Roche's pharmaceutical business generated CHF 46 billion (about $50.7 billion), marking an 8% increase, while the diagnostics division saw revenues of CHF 14.3 billion (approximately $15.7 billion), up 7%. The pharmaceutical segment remains the main source of Roche's profits. The company's pharmaceutical portfolio includes targeted therapies across five key areas: oncology, immunology, neuroscience, hematology, and ophthalmology. The ophthalmology sector showed remarkable growth in 2024, with sales reaching CHF 4 billion, reflecting a 44% increase. All other therapeutic areas also maintained positive growth trajectories. The drug Vabysmo (faricimab), launched in early 2022, continued to be a major growth driver, with sales of CHF 3.864 billion (about $4.243 billion) driven by increasing demand across all regions. Vabysmo is approved for three major retinal diseases, including wet age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. Looking ahead, Roche's pipeline is robust, featuring 71 new molecular entities (NMEs) and a total of 122 projects. However, the financial report indicated that the company has reduced ten projects in Q4 2024, primarily in early development stages. Notably, Roche made significant cuts to its TIGIT antibody RG6058 pipeline, including two Phase III trials, two Phase II trials, and one Phase I trial. Several early-stage projects were also removed from the pipeline, including: A Phase I study of the FAP/4-1BB bispecific antibody RG7827 for solid tumors. A Phase I study of the HER2/CD3 bispecific antibody RG6194 for breast cancer. Additional Phase I projects targeting various solid tumors. The TIGIT monoclonal antibody RG6058, which had been the first TIGIT antibody to enter Phase III trials globally. Roche also removed two Phase II trials for the TIGIT antibody targeting metastatic head and neck squamous cell carcinoma and non-small cell lung cancer, alongside two Phase III trials. In recent updates, Roche faced setbacks with the TIGIT antibody in 2024. The SKYSCRAPER-06 study, which evaluated the combination of tiragolumab, Tecentriq, and chemotherapy against pembrolizumab and chemotherapy for locally advanced non-squamous NSCLC, did not meet its primary endpoint, showing a hazard ratio of 1.27 for progression-free survival. Currently, Roche's TIGIT antibody pipeline includes five ongoing Phase III studies, focusing on NSCLC, esophageal cancer, and liver cancer. Looking forward, Roche anticipates the potential for over seven new molecular entities with peak sales exceeding CHF 3 billion, along with four additional entities with peak sales between CHF 2 billion and 3 billion.

Phase 1Drug ApprovalFinancial StatementPhase 2Phase 3

100 Deals associated with Tiragolumab

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
PD-L1 positive Non-Small Cell Lung Cancer	Phase 3	China	F. Hoffmann-La Roche Ltd.	01 Mar 2024
PD-L1 positive Non-Small Cell Lung Cancer	Phase 3	China	Genentech, Inc.	01 Mar 2024
PD-L1 positive Non-Small Cell Lung Cancer	Phase 3	China	Roche China Holding Ltd.	01 Mar 2024
Hepatocellular Carcinoma	Phase 3	United States	Roche Holding AG	14 Sep 2023
Hepatocellular Carcinoma	Phase 3	China	Roche Holding AG	14 Sep 2023
Hepatocellular Carcinoma	Phase 3	Japan	Roche Holding AG	14 Sep 2023
Hepatocellular Carcinoma	Phase 3	Belgium	Roche Holding AG	14 Sep 2023
Hepatocellular Carcinoma	Phase 3	Brazil	Roche Holding AG	14 Sep 2023
Hepatocellular Carcinoma	Phase 3	Canada	Roche Holding AG	14 Sep 2023
Hepatocellular Carcinoma	Phase 3	Côte d'Ivoire	Roche Holding AG	14 Sep 2023

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04300647 (SKYSCRAPER-04, CTgov)	Phase 2	PD-L1 positive Uterine Cervical Cancer	172	atezolizumab (Atezolizumab)	qooulfffra = hatintghyi hubixacnhi (ekvhxftlke, ruwcoqqcls - npogjykzim) View more	-	25 Mar 2025
				atezolizumab+Tiragolumab (Tiragolumab Plus Atezolizumab)	qooulfffra = qkikxornsh hubixacnhi (ekvhxftlke, sicejlsxco - sokazenbih) View more
NCT04524871 (MORPHEUS-Liver, Pubmed \| Lancet Oncol) Manual	Phase 1/2	Hepatocellular Carcinoma	58	TiragolumabTiragolumab 600 mg + Atezolizumab 1200 mg + Bevacizumab 15 mg/kgBevacizumab 15 mg/kg	klqpcjcvyd(lacwqyuivm) = The incidence of pruritis (20 [50%] of 40 patients vs three [17%] of 18 patients), arthralgia (13 [33%] vs two [11%]), and diarrhoea (12 [30%] vs one [6%]) was notably higher in the tiragolumab plus atezolizumab plus bevacizumab group than in the atezolizumab plus bevacizumab group, although these were mainly grade 1-2. lpgpwmhjrv (djyydeoxcm ) View more	Positive	21 Jan 2025
				Atezolizumab 1200 mg + BevacizumabBevacizumab 15 mg/kg
NCT04619797 (SKYSCRAPER-06, ESMO_IO2024) Manual	Phase 2/3	Advanced Lung Non-Squamous Non-Small Cell Carcinoma Maintenance	542	Tiragolumab 600 mg IV + Atezolizumab 1200 mg IV + Carboplatin/Cisplatin + Pemetrexed IV	rfvqjrzrjt(ndmvyfwmzn) = ksprzunodx oiwtyvwesf (nylvyjhfun, 15.2 - 23.8) View more	Negative	12 Dec 2024
				Placebo + Pembrolizumab 200 mg IV + Carboplatin/Cisplatin + Pemetrexed IV	rfvqjrzrjt(ndmvyfwmzn) = ydqkkmswvi oiwtyvwesf (nylvyjhfun, 20.7 - 33.0) View more
NCT04294810 (SKYSCRAPER-01, GlobeNewswire) Manual	Phase 3	PD-L1 positive Non-Small Cell Lung Cancer PD-L1 High Expression	534	tiragolumab + Tecentriq	cnqrceuzpn(mreykhtssq) = did not reach the primary endpoint. mcxakcssmy (kpfcpgbcml ) Not Met View more	Negative	26 Nov 2024
				Placebo + Tecentriq
NCT05315713 (CTgov)	Phase 1/2	Follicular Lymphoma \| B-cell lymphoma refractory	8	Mosunetuzumab SC+tocilizumab+Tiragolumab	ikpocmlxxp = qmtialamjh ytzkdkudit (oyktbqlsup, zlytgnawzd - kisscbpiek) View more	-	04 Oct 2024
NCT04619797 (SKYSCRAPER-06, Company_Website) Manual	Phase 2/3	Metastatic Non-Squamous Non-Small Cell Lung Carcinoma First line	542	tiragolumab+Tecentriq+chemotherapy	mthgqiigas(itivecamee): HR = 1.27 (95% CI, 1.02 - 1.57) Not Met View more	Negative	03 Jul 2024
				Placebo+pembrolizumab+chemotherapy
NCT04300647 (SKYSCRAPER-04, AACR2024)	Phase 2	Uterine Cervical Cancer PD-L1+ \| TIGIT \| TAP ... View more	171	Tiragolumab plus atezolizumab dual blockade (T+A)	xivaboelpp(dppfbtankj) = gcwyzmljix znghnhbdbp (whuecuqnvi )	Positive	22 Mar 2024
NCT04256421 (SKYSCRAPER-02, Pubmed) Manual	Phase 3	Extensive stage Small Cell Lung Cancer First line \| Maintenance	490	Tiragolumabatezolizumabcarboplatinetoposide	ncjcuuzdkr(drzkimnhur) = lyicxjsdlc jifvlavwmk (lfdsvkwucl ) View more	Negative	20 Jan 2024
				AtezolizAtezolizumabrbocarboplatinetoetoposideE)	ncjcuuzdkr(drzkimnhur) = wyyvnhdqbl jifvlavwmk (lfdsvkwucl ) View more
NCT04540211 (SKYSCRAPER-08, ASCO_GI2024) Manual	Phase 3	Esophageal Squamous Cell Carcinoma First line PD-L1	461	Tiragolumab 600mg + Atezolizumab 1200mg + Chemotherapy	mkqueavred(bzghqrdzjs) = jyozebqaee qcojpljugy (efnowokjlr ) View more	Positive	18 Jan 2024
				Placebo + Chemotherapy	mkqueavred(bzghqrdzjs) = llxxpknfiz qcojpljugy (efnowokjlr ) View more
NCT03281369 (MORPHEUS-EC, ASCO_GI2024) Manual	Phase 1/2	Esophageal Carcinoma First line	152	Cisplatin + 5-FU	nzjchldrcr(vqsbowrqwp) = gomyixrqxr jaeoagvoqn (smwvsovayk, 26.8 - 69.4) View more	Positive	18 Jan 2024
				Atezolizumab + Cisplatin + 5-FU	nzjchldrcr(vqsbowrqwp) = smsztqvcrk jaeoagvoqn (smwvsovayk, 41.0 - 66.3) View more

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