LIGHTBEAM-U01 Substudy 01B: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors

This study is a rolling arm study of pembrolizumab in combination with investigational agents in pediatric participants with relapsed or refractory classical Hodgkin lymphoma (cHL) solid tumors with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) or tumor mutational burden-high (TMB-H). This study will have 2 parts: a safety lead-in to demonstrate a tolerable safety profile and confirm a preliminary recommended phase 2 dose (RP2D) (Part 1) followed by an efficacy evaluation (Part 2). Participants will be assigned to a treatment arm (either Part 1 or Part 2) that is open for enrollment.
There will be no hypothesis testing in this study.

Start Date15 Jan 2025

Sponsor / Collaborator

Merck Sharp & Dohme LLC

NCT04303169

/ Active, not recruitingPhase 1/2

A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02C

Substudy 02C is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study.
The goal of substudy 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.
Arm 1: Pembrolizumab + Vibostolimab, Arm 2: Pembrolizumab + Gebasaxturev, and Arm 3: Pembrolizumab were added in the base protocol on 13-Nov-2019, and enrollment into those arms has been completed. Arm 4: Pembrolizumab + MK-4830 was added in Amendment 04 on 20-Dec-2021, and enrollment into that arm has been completed. Arm 5: Favezelimab + Pembrolizumab and Arm 6: Pembrolizumab + all-trans retinoic acid (ATRA) were added in Amendment 06 on 25-Jun-2022, and enrollment is ongoing.

Start Date26 Jun 2020

Sponsor / Collaborator

Merck Sharp & Dohme LLC

NCT04165070

/ RecruitingPhase 1/2

KEYMAKER-U01 Substudy 01A: A Phase 1/2, Umbrella Study With Rolling Arms of Investigational Agents With Pembrolizumab With or Without Chemotherapy in Treatment-Naive Participants With Stage IV Non-small Cell Lung Cancer (NSCLC)

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) with or without chemotherapy in combination with vibostolimab (MK-7684), boserolimab (MK-5890), MK-4830, MK-0482, I-DXd, or HER3-DXd in treatment-naïve participants with advanced squamous or non-squamous NSCLC.
This study is one of the pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

Start Date19 Dec 2019

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

[+1]

100 Clinical Results associated with Vibostolimab

100 Translational Medicine associated with Vibostolimab

100 Patents (Medical) associated with Vibostolimab

Literatures (Medical) associated with Vibostolimab

01 Jan 2025·NATURE MEDICINE

Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB–D melanoma: a phase 1/2 trial

Article

Author: Menzies, Alexander M ; Hill, Andrew ; Long, Georgina V ; Grob, Jean-Jacques ; Khattak, Muhammad A ; Robert, Caroline ; Dummer, Reinhard ; Shapira-Frommer, Ronnie ; Mehmi, Inderjit ; Meyer, Nicolas ; Fukunaga-Kalabis, Mizuho ; Portnoy, David C ; Lebbe, Celeste ; Tetzlaff, Michael T ; Cohen, Jonathan ; Bar-Sela, Gil ; Krepler, Clemens ; Webber, Andrea L ; Ren, Yixin ; Taube, Janis M ; Scolyer, Richard A

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy. Pathologic complete responses occurred in 10 of 26 patients (38%) with pembrolizumab plus vibostolimab, 7 of 25 (28%) with pembrolizumab plus gebasaxturev and 6 of 15 (40%) with pembrolizumab monotherapy. Major pathologic responses occurred in 13 (50%), 10 (40%) and 7 (47%) patients, respectively. Safety was manageable. Treatment-related adverse events occurred in 24 of 26 patients (92%) with pembrolizumab plus vibostolimab, 21 of 25 (84%) with pembrolizumab plus gebasaxturev and 12 of 15 (80%) with pembrolizumab monotherapy; grade 3 or 4 treatment-related adverse events occurred in 2 (8%), 7 (28%) and 1 (7%) patient in each arm, respectively. No deaths due to adverse events occurred. Exploratory objective responses per RECIST v1.1 were observed in 13 (50%), 8 (32%) and 4 (27%) patients, in each arm, respectively. In a post hoc analysis, scores for tumor mutational burden and an 18-gene T cell-inflamed gene expression profile were generally higher in patients with major pathologic response. Longer follow-up will provide insight into the incremental benefit of combining neoadjuvant pembrolizumab with other therapies in stage IIIB-D melanoma. ClinicalTrials.gov registration: NCT04303169 .

26 Aug 2024·Future Oncology

The KEYVIBE program: vibostolimab and pembrolizumab for the treatment of advanced malignancies

Article

Author: Ahn, Myung-Ju ; Peters, Solange ; Shouse, Geoffrey ; Lugowska, Iwona ; Garassino, Marina C. ; Sands, Jacob ; Zhao, Bin ; Niu, Jiaxin ; Keenan, Tanya ; Healy, Jane ; Perets, Ruth ; Shapira-Frommer, Ronnie

Vibostolimab, a humanized IgG1 monoclonal antibody, blocks the interaction between TIGIT and its ligands, preventing the immunosuppressive effects of TIGIT. The addition of vibostolimab to the PD-1 inhibitor pembrolizumab has shown promising antitumor activity, warranting further exploration of vibostolimab as a potential therapeutic option. The KEYVIBE program consists of nine trials that will evaluate the safety and efficacy of vibostolimab monotherapy and vibostolimab-based combination therapy in advanced solid tumors and hematological malignancies. These studies will also evaluate coformulated immunotherapy addressing issues that occur with the sequential administration of immunotherapy. The KEYVIBE program will provide further insight into the clinical utility of vibostolimab-based therapy across multiple indications and various stages of disease.

01 Aug 2023·Cancer letters

TIGIT immune checkpoint blockade enhances immunity of human peripheral blood NK cells against castration-resistant prostate cancer

Article

Author: Xing, Nianzeng ; Wang, Jing ; Li, Jianxing ; Ma, Jianlin ; Wang, Fangming ; Liu, Fei ; Yang, Feiya ; Liang, Jing ; Xu, Tianli ; Liu, Shuai ; Liu, Donghua

Castration-resistant prostate cancer (CRPC) patients have a 14-month median survival, emphasizing the need for alternative treatments. Previously, we demonstrated that expanded high-dose natural killer (NK) cells derived from human peripheral blood exhibit therapeutic efficacy against CRPC. However, which immune checkpoint blockade promotes NK cell antitumor immunity against CRPC remains unknown. Here, we explored immune checkpoint molecule expression in NK and CRPC cells during their interactions, and identified that the T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) monoclonal antibody (mAb), vibostolimab, significantly enhanced NK cell cytotoxicity against CRPC cells and cytokine production in vitro, demonstrated by upregulation of degranulation marker CD107a and Fas-ligand (Fas-L) and increased interferon-gamma (IFN-γ) and tumor necrosis factor-alpha secretion. TIGIT blockade increased Fas-L expression and IFN-γ production via the NF-κB signaling pathway and restored degranulation via the mitogen-activated protein kinase ERK (extracellular signal-regulated kinase) kinase/ERK pathway in activated NK cells. Vibostolimab significantly enhanced NK cell antitumor effects against CRPC in two xenograft mouse models. Vibostolimab also increased T cell chemotaxis induced by activated NK cells in vitro and in vivo. Overall, blocking TIGIT/CD155 signaling enhances the antitumor effect of expanded NK cells against CRPC; this finding supports the translational application of TIGIT mAb and NK cell combination strategies from bench to bedside for CRPC treatment.

News (Medical) associated with Vibostolimab

14 May 2025

·www.pharmaceutical-technology.com

GSK and iTeos drop anti-TIGIT drug following trial failure

GSK and iTeos have said they are stopping all development programmes for their anti-TIGIT antibody belrestotug. Image credit: Shutterstock / FON’s Fasai. GSK and iTeos are the latest companies to scrap a jointly developed anti-TIGIT drug after it failed to demonstrate a meaningful benefit in two Phase II trials. Belrestotug, a human IgG1 antibody created to bind with high-affinity T cell immunoglobulin and ITIM domains (TIGIT), was being developed as part of a partnership harnessed between the companies in June 2021 . The companies announced on 13 May that they were slashing the programme after receiving new interim analyses from the Phase II GALAXIES Lung-201 (NCT05565378) and GALAXIES H&N-202 (NCT06062420) studies, which did not meet their efficacy endpoints. Both trials were investigating the drug in combination with the PD-1 monoclonal antibody Jemperli (dostarlimab). However, the GALAXIES Lung-201 study was in patients with previously untreated, advanced/metastatic non-small-cell lung cancer (NSCLC). Meanwhile, the GALAXIES H&N-202 trial was in patients with PD-L1 positive recurrent/metastatic squamous cell carcinoma of the head and neck. iTeos reported that while the GALAXIES Lung-201 trial demonstrated clinically meaningful improvements in the primary endpoint of objective response rate (ORR), however, the analysis did not meet established criteria for clinically meaningful improvements in the secondary endpoint of progression-free survival (PFS). Analysis from the GALAXIES H&N-202 trial showed a trend below the meaningful threshold for ORR in the combination cohort. In a company statement, GSK says that due to the failures, the collaboration and all belrestotug study cohorts are ending. iTeos clarified that this includes enrolment in the ongoing GALAXIES Lung-301 Phase III trial. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence iTeos’ president and chief executive officer Dr Michel Detheux said: “We are truly disappointed by the results from GALAXIES Lung-201. Following the analysis of the TIGIT data generated to date with GSK, we have made the mutual decision to discontinue the development of all ongoing TIGIT studies.” GSK joins pharma giants dropping anti-TIGIT drugs The news may come as a shock to the oncology field, as GSK and iTeos provided the first data for the GALAXIES Lung-201 study at the European Society for Medical Oncology (ESMO) Congress 2024 last September. The data seemed to show a positive trend with an ORR of between 63.3% and 76.7% versus 37.5% for Jemperli as a monotherapy. The mechanism has proven challenging, with GSK and iTeos becoming the latest companies to terminate an anti-TIGIT asset. Last month, BeiGene announced it was terminating development of ociperlimab , which it had been manufacturing as a treatment for lung cancer. In December 2024, MSD scrapped the development of its anti-TIGIT antibody vibostolimab after the Phase III KeyVibe-003 and KeyVibe-007 trials met the pre-specified futility criteria for the primary endpoint of overall survival (OS) in patients with NSCLC. The company stopped the KeyVibe-008 trial last year . In November 2024, Roche reported a failure with its candidate tiragolumab , which was being trialled in the Phase III Skyscraper-01 study. This came after earlier setbacks in the SKYSCRAPER-02 (NCT04256421) study and the Phase II/III SKYSCRAPER-06 (NCT04619797) trial. Some anti-TIGIT programmes are still steaming ahead, including one by Gilead and Arcus Biosciences; who are investigating domvanalimab , and another by AstraZeneca with its PD-1/TIGIT bispecific antibody rilvegostomig .

Phase 2Phase 3Phase 1Clinical Trial TerminationClinical Result

14 May 2025

·www.biospace.com

GSK, iTeos Abandon TIGIT Therapy, Adding to Long List of Recent Class Failures

iStock, nndanko Belrestotug showed underwhelming efficacy outcomes in mid-stage studies of non-small cell lung cancer and head and neck squamous cell carcinoma. GSK and Massachusetts-based partner iTeos Therapeutics will no longer advance their investigational TIGIT therapy belrestotug following disappointing mid-stage results, GSK announced on Tuesday. The decision adds another therapy to the spate of failed TIGIT therapies across the industry. “The collaboration [with iTeos] and all belrestotug-containing study cohorts are ending,” GSK wrote in its news release. The decision to discontinue the development of belrestotug was “mutual,” iTeos CEO Michel Detheux said in a statement alongside the biotech’s own announcement. In the aftermath of belrestotug’s discontinuation—and of losing a powerhouse partner—iTeos is “taking immediate steps” to shore up its financial position. The biotech on Tuesday kicked off a “targeted” strategic review of its business to identify opportunities to maximize capital and value to shareholders, as per its press announcement. GSK and iTeos were studying belrestotug in the Phase II GALAXIES Lung-201 study in non-small cell lung cancer (NSCLC). Topline results from this trial, reported Tuesday, showed that while the TIGIT therapy did meet its primary endpoint of objective response rate, it was unable to elicit “clinically meaningful improvements in . . . progression-free survival,” a key secondary outcome of the study, according to iTeos’ release. The partners were also running the GALAXIES H&N-202 Phase II study in head and neck squamous cell carcinoma. GALAXIES H&N-202 also delivered disappointing results, with belrestotug showing a “trend below the meaningful threshold for” objective response rate. GALAXIES Lung-201 and GALAXIES H&N-202 paired belrestotug with GSK’s PD-1 blocker Jemperli and compared the combo against Jemperli alone. The companies did not provide specific figures for either study on Tuesday, though Detheux noted that “it is important to share these data with the scientific community at an upcoming medical meeting.” GSK and iTeos came together for this collaboration in 2021 , in a deal that had GSK paying iTeos $625 up front and up to $1.45 billion in downstream milestone payments. Belrestotug joins the growing group of TIGIT treatments that have been shelved over the past year, highlighting the difficulties of developing therapies in this class. Last month, for instance, BeiGene announced that it would no longer pour money into its anti-TIGIT antibody ociperlimab, which it had been assessing for NSCLC. An independent data monitoring committee found that the Phase III AdvanTIG-302 trial was “unlikely to meet the primary endpoint of overall survival.” In July 2024, Roche likewise dumped its TIGIT candidate tiragolumab after disappointing data from the Phase II/III SKYSCRAPER-06 trial in NSCLC. This followed Merck’s May 2024 discontinuation of a late-stage study for the anti-TIGIT treatment vibostolimab, which it was combining with its blockbuster Keytruda as a treatment for melanoma.

Phase 2Phase 3Clinical ResultClinical Trial FailureClinical Trial Termination

03 Apr 2025

·www.fiercebiotech.com

BeiGene abandons ociperlimab over poor phase 3 prospects in latest blow to TIGITs

A BeiGene study’s independent data monitoring committee recommended terminating a phase 3 trial of ociperlimab.\n BeiGene is scrapping ociperlimab over a disappointing phase 3 outlook two years after Novartis handed back the anti-TIGIT antibody.The global biopharma had been evaluating ociperlimab, alongside BeiGene’s own PD-1 inhibitor Tevimbra, when compared to Merck & Co.\'s megablockbuster cancer med Keytruda in patients with PD-L1-high, locally advanced/recurrent or untreated metastatic non-small cell lung cancer. BeiGene, which is in the process of rebranding to BeOne Medicines, enrolled the first patient in the late-stage study back in 2021, with the aim of assessing the dual targeting of anti-TIGIT and anti-PD-1 antibodies.However, the study’s independent data monitoring committee recommended terminating the phase 3 trial after an early analysis suggested it would miss its primary endpoint of overall survival.After “thorough deliberation,” the study has been terminated, said BeiGene, which pointed out that no new safety signals had been observed.“We evaluate our clinical programs to focus our resources on the most promising clinically differentiated candidates while thoughtfully de-prioritizing others,” Mark Lanasa, M.D., Ph.D., chief medical officer for solid tumors at BeiGene, said in the April 3 release.Pharmas have previously pumped vast sums of money into licensing and developing anti-TIGIT antibodies in the belief they can counter a way tumors suppress immune responses. However, the results have so far failed to justify the outlay. Novartis paid $300 million to enter the TIGIT space by acquiring ociperlimab in 2021 but handed the asset back to BeiGene two years later. A Novartis spokesperson told Fierce Biotech at the time that the decision had been made after assessing \"the totality of the current information, including phase 2 data, benefit/risk, competitive space, timing, development programs, and future investments.\"Meanwhile, Roche’s TIGIT drug tiragolumab has failed a trio of phase 3 trials in various types of lung cancer. Arcus Biosciences and Gilead Sciences also stopped a study in the setting at the start of last year, while Merck ended 2024 by jettisoning its TIGIT prospect vibostolimab.But it’s not over for TIGITs quite yet. Roche hasn’t fully given up on tiragolumab, while GSK began a phase 3 trial of its iTeos Therapeutics-partnered prospect belrestotug last year

Phase 3AcquisitionPhase 2Clinical Trial Failure

100 Deals associated with Vibostolimab

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D11795	-	-	DB16420

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Phase 3	United States	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	China	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	Chile	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	Guatemala	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	Russia	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	South Korea	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	Turkey	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	Ukraine	Merck Sharp & Dohme Corp.	07 Apr 2021
Turcot Syndrome	Phase 2	United States	Merck Sharp & Dohme LLC	15 Jan 2025
Turcot Syndrome	Phase 2	Taiwan Province	Merck Sharp & Dohme LLC	15 Jan 2025

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04303169 (KEYMAKER-U02, ESMO2024) Manual	Phase 1/2	Melanoma	117	Pembrolizumab + Vibostolimab	wqcxqervzb(ckqfhpobvl) = metcylfptp iznovahosy (acsbusjssm ) View more	Positive	14 Sep 2024
				Pembrolizumab + Gebasaxturev	wqcxqervzb(ckqfhpobvl) = rlctuidsey iznovahosy (acsbusjssm ) View more
TIGIT (NEWS) Manual	Phase 2	metastatic non-small cell lung cancer	-	vibostolimab+Keytruda	lpxdpbigwf(dzlhjcpkdu) = krfdgcartv smwztpyrce (xnfagvrgzi ) View more	Negative	07 Dec 2023
				docetaxel	lpxdpbigwf(dzlhjcpkdu) = parfydftvo smwztpyrce (xnfagvrgzi ) View more
NCT04303169 (KEYMAKER-U02 substudy 02C \| 3475-02C \| KEYMAKER-U02 \| MK-3475-02C, AACR2023) Manual	Phase 1/2	Melanoma Neoadjuvant	66	pembrolizumab+vibostolimab (arm 1)	fgctzhftug(fzutnikofp) = qkohequnoa bippvrrqqw (wyepcixhfo ) View more	Positive	14 Apr 2023
				pembrolizumab+gebasaxturev (arm 2)	fgctzhftug(fzutnikofp) = uomonorrxi bippvrrqqw (wyepcixhfo ) View more
NCT02964013 (KEYVIBE-001, ESMO_GI2022)	Phase 1	Advanced gastric carcinoma PD-L1-positive	27	Vibostolimab 200mg + Pembrolizumab 200mg	spcbwzxytq(gnjplwinkb) = whempamwxx xqgjpidihl (xtwffihcmi ) View more	Positive	02 Jul 2022
NCT02964013 (MK-7684-001, AACR2022) Manual	Phase 1	Uterine Cervical Cancer Third line	80	vibostolimab 200 mg+pembrolizumab	ogiyruszhl(ihluwpqorn) = nazaslloov vqpnrpvrxh (qbblfjrzah ) View more	Positive	15 Jun 2022
				vibostolimab 700 mg+pembrolizumab	ogiyruszhl(ihluwpqorn) = csamrojwed vqpnrpvrxh (qbblfjrzah ) View more
NCT02964013 (MK-7684-001 \| KEYVIBE-001 \| 7684-001, AACR2022) Manual	Phase 1	Ovarian Cancer Second line PD-L1 Expression	61	vibostolimab+pembrolizumab	-	Positive	15 Jun 2022
				vibostolimab/pembrolizumab
NCT02964013 (MK-7684-001 \| KEYVIBE-001 \| 7684-001, ESMO2020) Manual	Phase 1	Non-Small Cell Lung Cancer	79	Vibostolimab	njtdbqqxhm(ouagtnczqz) = ivkbpkxoaf ingaiiokoy (uchcwukwal ) View more	Positive	17 Sep 2020
				Vibostolimab+pembrolizumab	njtdbqqxhm(ouagtnczqz) = qusipobeyp ingaiiokoy (uchcwukwal ) View more
NCT02964013 (MK-7684-001 \| KEYVIBE-001 \| 7684-001, ESMO2020) Manual	Phase 1	Non-Small Cell Lung Cancer	41	Pembrolizumab+vibostolimab	qdfgggaugu(ttlnkvuqjt) = zbabwztjuu elzhxsvmfr (sctkebumcs ) View more	Positive	17 Sep 2020

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