The proposed study is an observational, prospective, multicenter study of patients undergoing neoadjuvant therapy for medium-low rectal cancer.
Recently the investigators have published the findings of a multicenter Italian phase II study showing that the rate of local recurrence, with a 3 year follow-up, is less than 5% in patients with baseline T2-3 mid-low rectal cancer who, after preoperative chemoradiotherapy (pCRT), showed a major clinical response and underwent a transanal local excision. Based on these results, an organ-sparing approach for patients showing a major clinical response is feasible without reducing the good results obtained with the standard treatment. While a phase III trial is the best way to compare the standard treatment with the organ-sparing approach (local excision or wait-and-see) it is impracticable and likely unethical. An observational study is therefore one of the best way to evaluate the impact that an organ-sparing approach may have on oncological outcomes, quality of life, and bowel function for patients with rectal cancer who, after a pCRT, show a clinical major/complete response.
This phase II trial is designed to test the hypothesis that conservative treatments, in patients with low-mid rectal cancer who undergo a major or complete clinical response after neoadjuvant treatment, will be safe and effective compared to standard surgery.
The investigators will compare rectum-sparing approaches to standard surgery, firstly in terms of rate of organ preservation at 2 years. Additionally they will compare survival outcomes (DFS, OS), stoma rates, clinical and tumor factors related to pathological complete response, correlation between major and complete clinical response.
To add value, the investigators will measure QoL in patients treated with rectum-sparing approaches in comparison to patients treated with standard surgery (TME or abdomino-perineal amputation).
Rectum-sparing approach can be considered clinically acceptable if percentage of conservation of the rectum at two years is not less than 50%.
The collected data on 164 patients who underwent "rectum-sparing" allow to test the hypothesis that the rectum is preserved in 60% of patients with 80% power (exact binomial test for proportions, alpha = 5 %, 1 tail) and the study will be considered positive if it obtains a frequency of conservation of the rectum of not less than 87 cases.
The analysis results will be reported in accordance with STROBE guidelines (von Elm et al., 2008). For all analyzes, continuous variables are described using the mean and standard deviation of position and appropriate measures when appropriate. Categorical variables will be described using the contingency tables.

Start Date01 Jan 2016

Sponsor / Collaborator

University of Padua

[+5]

NCT01983124

/ CompletedPhase 2IIT

A Phase II Single-arm Study for the Treatment After Recurrence of Advanced Melanoma Patients Harboring the V600BRAF Mutation and Pretreated With Vemurafenib, With the Association of Vemurafenib Plus Fotemustine.

The purpose of this study is to evaluate the activity of Vemurafenib in combination with Fotemustine in Patients with unresectable Stage IV melanoma harboring V600 BRAF mutation who recurred while in treatment with Vemurafenib. In addition the feasibility and safety profile of prolonging treatment of this drugs combination will be assessed.

Start Date01 Feb 2013

Sponsor / Collaborator

Istituto Nazionale Dei Tumori

NCT01046994

/ Unknown statusPhase 3IIT

Prospective Controlled Trial on Surgical Treatment of Type 2 Diabetes Patients With BMI 25-30 by Means of Biliopancreatic Diversion

A previous prospective study of BPD effect on type 2 diabetes patients with BMI 25-35 (DIA-CHIR) showed that T2DM is less sensitive to BPD beneficial effect in the simply overweight patients. A new prospective study was then planned with the aim to gain insight in the mechanism of action of BPD in T2DM patients in the 25-30 BMI range. Thirty patients will be submitted to BPD and compared with 10 nonoperated controls. Euglycemic-hyperinsulinemic clamp, OGTT, and mixed meal test will be performed in all subjects preoperatively, and 1 month, 1 year, and 5 years after BPD. Complete clinical and biochemical evaluations will be performed at 1, 4, 8, and 12 months, and every sixth month thereafter until the end of the fifth year.

Start Date01 Jul 2009

Sponsor / Collaborator

Istituto Nazionale Dei Tumori

100 Clinical Results associated with Istituto Nazionale Dei Tumori

0 Patents (Medical) associated with Istituto Nazionale Dei Tumori

788

Literatures (Medical) associated with Istituto Nazionale Dei Tumori

31 Dec 2025·mAbs

Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production

Article

Author: Carroll, Simon ; McCraw, Alexandra J ; Stavraka, Chara ; Selkirk, Chris ; Vigor, Kim ; Hillyer, Tim ; Westwood, Nigel ; Lentfer, Heike ; Gardner, Richard A ; Urbanowicz, Paulina A ; Spencer, Daniel I R ; Figini, Mariangela ; Chauhan, Jitesh ; Grandits, Melanie ; Karagiannis, Sophia N ; Spicer, James ; Josephs, Debra H ; Bax, Heather J ; Cheeseman, Jack ; Mellor, Sarah

Antibodies used for cancer therapy are monoclonal IgGs, but tumor-targeting IgE antibodies have shown enhanced effector cell potency against cancer in preclinical models. Research-grade recombinant IgE antibodies have been generated and studied for several decades. The recent Phase 1 clinical trial of the first-in-class MOv18 IgE, however, necessitated the inaugural process development and scaled manufacture of a recombinant IgE to clinical quality standards. During the process development and scaled Good Manufacturing Practice production, we demonstrate the retention of glycosylation state, biophysical profile, and functional characteristics of MOv18 IgE, including Fc-mediated mast cell degranulation and tumor cell killing. Assessment of manufacturing parameters shows expected pH, purity, concentration, and stability properties, as well as below threshold levels of known biological manufacturing contaminants. We confirm the suitability of the pipeline described for generating intact, functionally active, clinical-grade material for this novel therapeutic class as an Investigational Medicinal Product (IMP), with comparable characteristics to the original research-grade antibody. Furthermore, we screened patient blood ex vivo for potential type I hypersensitivity reaction to MOv18 IgE, using the basophil activation test, to identify patients not predicted to be hypersensitive to MOv18 IgE administration. This study supports the production of functionally active clinical grade (IMP) recombinant IgE and paves the way for the development of a new therapeutic antibody class for a range of antigenic specificities and disease settings.

21 Apr 2025·Cancer Research

Abstract 7148: Exploratory biomarker analysis of trastuzumab deruxtecan (T-DXd) treatment for HER2-positive (HER2+) metastatic colorectal cancer (mCRC) in DESTINY-CRC02 (DC-02)

Author: Shiose, Yoshinobu ; Andre, Thierry ; Raghav, Kanwal ; Lonardi, Sara ; Pietrantonio, Filippo ; Peeters, Marc ; Koga, Makito ; Van den Eynde, Marc ; Yamaguchi, Kensei ; Takashima, Atsuo ; Haribhai, Dipica ; Tie, Jeanne ; Barrios, Daniel ; Yoshino, Takayuki ; Castro, Cristina Gravalos ; Strickler, John H. ; Komatsu, Yoshito ; Kawakami, Hisato ; Siena, Salvatore ; Boran, Aislyn ; Goto, Hiroki ; Abe, Kodai ; Kato, Takeshi

AbstractBackground:T-DXd showed clinically meaningful antitumor activity in patients (pts) with HER2+ mCRC in the phase 2 DC-02 trial (NCT04744831). Exploratory baseline circulating tumor DNA (ctDNA) analyses of HER2 (ERBB2), PIK3CA, and RAS mutation (mut) status and blood-based tumor mutational burden were reported previously (Raghav et al. 2024). This study reports the relationship between other CRC-related genes and efficacy of T-DXd in HER2+ mCRC.MethodsFor this analysis, data were combined from 122 pts enrolled in the 5.4 and 6.4 mg/kg T-DXd cohorts. Transcriptome analysis by RNA sequencing with ribosome depletion was performed on 102/107 available baseline (BL) archival tissue samples. ctDNA from blood collected at BL (n = 120/120) and after 2 T-DXd treatment cycles (C3D1; n = 97/103 paired BL/C3D1 samples) was analyzed at Guardant Health to determine genomic landscape (OMNI, ∼500 genes) and molecular response (MR; G360, ∼74 genes).Results:By ctDNA, alterations (any) in TP53 (84.2%), APC (77.5%), FLT3 (63.3%), and PREX2 (52.5%) were most common; 82.5% and 24.2% of pts had HER2 amplification (amp) or mut, respectively. Pts with APC mut or ≥ median ABCB1 (P-gp) transporter gene expression tended to have lower objective response rate (ORR) and shorter median progression-free survival (PFS; Table). PFS appeared to be shorter in pts with EGFR amp (Table), although this group also had higher ctDNA levels, which is negatively prognostic. Complete MR at C3D1 was associated with the highest ORR and longest PFS, while ORR was lowest and PFS shortest when MR was absent (Table).Conclusions:Several genetic biomarkers with known prognostic effects in CRC, including EGFR or APC alterations, were potentially associated with T-DXd efficacy. MR analyses suggested magnitude of ctDNA reduction at C3D1 could be predictive of T-DXd clinical response. Further analysis is needed to assess these biomarkers’ predictive vs prognostic value.Citation Format:Salvatore Siena, Kanwal Raghav, Atsuo Takashima, Takeshi Kato, Marc Van den Eynde, Filippo Pietrantonio, Yoshito Komatsu, Hisato Kawakami, Marc Peeters, Thierry Andre, Sara Lonardi, Kensei Yamaguchi, Jeanne Tie, Cristina Gravalos Castro, John H. Strickler, Yoshinobu Shiose, Makito Koga, Aislyn Boran, Dipica Haribhai, Hiroki Goto, Daniel Barrios, Kodai Abe, Takayuki Yoshino. Exploratory biomarker analysis of trastuzumab deruxtecan (T-DXd) treatment for HER2-positive (HER2+) metastatic colorectal cancer (mCRC) in DESTINY-CRC02 (DC-02) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7148.

01 Apr 2025·The Lancet Oncology

Health-related quality of life with belzutifan versus everolimus for advanced renal cell carcinoma (LITESPARK-005): patient-reported outcomes from a randomised, open-label, phase 3 trial

Article

Author: Lam, Elaine T ; de Velasco, Guillermo ; Peltola, Katriina ; Powles, Thomas ; Gümüş, Mahmut ; Stadler, Walter M ; Ghatalia, Pooja ; Choueiri, Toni K ; Kollmannsberger, Christian ; Vickery, Donna ; Suarez, Cristina ; Burotto, Mauricio ; Poprach, Alexandr ; He, Li ; De Santis, Maria ; Saretsky, Todd L ; Gross-Goupil, Marine ; Rizzo, Mimma ; Albiges, Laurence ; Iacovelli, Roberto ; Rini, Brian ; Melichar, Bohuslav ; Perini, Rodolfo F ; Shinde, Reshma ; Venugopal, Balaji ; Verzoni, Elena

BACKGROUNDThe first-in-class hypoxia-inducible factor-2α (HIF-2α) inhibitor belzutifan is approved for patients with advanced renal cell carcinoma previously treated with immune checkpoint and anti-angiogenic therapy based on results of the phase 3 LITESPARK-005 trial. We present patient-reported outcomes (PROs) from LITESPARK-005.METHODSLITESPARK-005 was an open-label, multicentre, randomised, active-controlled phase 3 trial conducted at 147 hospitals and cancer centres in six regions. Eligible participants were 18 years or older with advanced clear cell renal cell carcinoma, had a Karnofsky Performance Status score of 70% or higher, had measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, had disease progression on or after treatment with anti-PD-1 or anti-PD-L1 immunotherapy and a VEGF tyrosine kinase inhibitor (in sequence or in combination), and had received no more than three previous systemic lines of therapy. Eligible participants were randomly assigned (1:1) centrally using interactive voice-response and web-response systems to receive either belzutifan 120 mg orally once daily or everolimus 10 mg orally once daily. Randomisation was stratified by International Metastatic Renal Cell Carcinoma Database Consortium prognostic score and number of previous VEGF-targeted or VEGF receptor-targeted therapies. The dual primary outcomes were progression-free survival and overall survival, results of which have been reported previously. In this study, prespecified secondary patient-reported outcomes (PROs) from LITESPARK-005 were assessed using the Functional Assessment of Cancer Therapy-Kidney Cancer Symptom Index: Disease Related Symptoms (FKSI-DRS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The PRO analysis population included all participants who received at least one dose of study therapy and completed at least one PRO assessment. Least-squares mean change from baseline in PROs at week 17 was assessed using a constrained longitudinal data analysis model. Time to deterioration in physical functioning (prespecified) and role functioning (post hoc), as assessed by the EORTC QLQ-C30, were also evaluated in the PRO analysis population. This trial is ongoing, closed to recruitment, and registered with ClinicalTrials.gov, NCT04195750.FINDINGSBetween March 10, 2020, and Jan 19, 2022, 996 participants were screened for eligibility and 746 participants were randomly assigned to belzutifan (n=374) or everolimus (n=372). The PRO full analysis set population included 366 participants in the belzutifan group and 354 in the everolimus group. Median time from randomisation to the database cutoff date (June 13, 2023) was 25·7 months (IQR 21·7-30·4). Completion rates for FKSI-DRS and QLQ-C30 were higher than 94% at baseline and higher than 55% at week 17 in each group. Change from baseline to week 17 in FKSI-DRS score (difference in least-squares mean between groups 1·5 [95% CI 0·7 to 2·2]) and QLQ-C30 global health status-quality of life (QOL) score (6·4 [3·2 to 9·6]) suggested stability with belzutifan versus worsening with everolimus. Change from baseline to week 17 was similar between groups for QLQ-C30 physical functioning (difference in least-squares mean 2·5 [95% CI -0·6 to 5·5]) and QLQ-C30 role functioning (4·2 [0·1 to 8·4]) subscale scores. Time to deterioration was similar between the belzutifan and everolimus groups for EORTC physical functioning (median 19·3 months [95% CI 11·1 to not reached] in the belzutifan group vs 13·8 months [10·6 to not reached] in the everolimus group; hazard ratio 0·93 [95% CI 0·72 to 1·20]) and role functioning (median 12·0 months [9·2 to not reached] vs 10·2 months [4·7 to 14·4]; 0·88 [0·69 to 1·11]).INTERPRETATIONBelzutifan for advanced renal cell carcinoma was associated with improved disease-specific symptoms and QOL compared with everolimus. Taken together with the efficacy and safety data from LITESPARK-005, belzutifan could offer a clinical benefit without compromising the QOL of patients in this setting.FUNDINGMerck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

News (Medical) associated with Istituto Nazionale Dei Tumori

13 Dec 2021

·rottapharmbiotech.com

Rottapharm Biotech announces the first patient dosed in the Phase 1/2 study of the EP4 receptor antagonist CR6086 combined with Agenus’ anti-PD-1 balstilimab in advanced colorectal cancer

December 13, 2021 Monza (Italy) – Rottapharm Biotech announces dosing the first patient in the Phase 1/2 study of CR6086 in combination with Agenus’ balstilimab (anti-PD-1) in advanced colorectal cancer at the National Cancer Institute (Istituto Nazionale dei Tumori) – Milan (Italy). Patients with colorectal cancers have limited treatment options, as most do not respond to PD-1 therapy or other immunotherapy regimens studied to date. Colorectal cancers represent one of the three most common cancers diagnosed, and the second leading cause of deaths across all cancer types globally. More than 80% of colorectal cancers are classified as mismatch repair-proficient (pMMR) and microsatellite stable (MSS) colorectal cancer (CRC), which correlates with low tumor mutation burden and poor immune cell infiltration within the tumor microenvironment (“cold tumors”). These patients generally do not benefit from PD-1 therapy alone and combination strategies with other immune-modulating therapies are necessary to address immune suppression in the tumor microenvironment and improve sensitivity to PD-1 therapy. The involvement of prostaglandin E2 (PGE2) in cancerogenesis has been known for decades. There is now growing evidence about the role of PGE2, via its EP4 receptor on different immune cells, as a key effector for the impaired immune response within the tumor microenvironment and the potential for an EP4 receptor antagonist to turn the tumor microenvironment into an immune-responsive (“hot”) tissue. Rottapharm Biotech is developing CR6086, a potent and selective small molecule antagonist of EP4. EP4 signaling broadly suppresses immune activity in the tumor microenvironment, contributing to treatment resistance and tumor progression. CR6086 is designed to increase the activity and infiltration of several different immune cell types – including T cells, natural killer cells, and dendritic cells – while blocking the immune suppressive role of PGE2 in the tumor microenvironment. Preclinical evidence suggests that CR6086 may work in combination with PD-1 therapy to promote durable, anti-tumor immune responses. CR6086 is a potential best-in-class EP4 receptor antagonist, based on its pharmacokinetics and pharmacodynamic profile, and has demonstrated a strong safety profile in >250 subjects treated to date. Balstilimab is a monoclonal antibody developed by Agenus Inc., belonging to the immune checkpoint inhibitor class, and is an inhibitor of programmed cell death 1 (PD-1) protein. It has been evaluated in >400 patients to date and has demonstrated strong clinical activity and an excellent safety profile in several tumor types, including cervical cancer (results published in Gynecologic Oncology this year). The Phase 1/2 clinical study aims at evaluating the safety and efficacy of CR6086 combined with balstilimab in patients with advanced pMMR/MSS metastatic CRC (mCRC). The primary endpoints are safety, tolerability, and preliminary efficacy, as determined by disease control rate. The secondary endpoints include objective response rate, duration of response, progression-free survival, and overall survival. Rottapharm Biotech’s clinical collaboration with Agenus offers a promising new combination therapy for patients with advanced pMMR/MSS mCRC where there is a high unmet need, and for a further range of potential applications in other immunotherapy-resistant tumors. Rottapharm Biotech Rottapharm Biotech is a research company dedicated to the discovery and development of innovative drugs. It is located in Monza (Italy) The company expertise in research and development includes medicinal / computational chemistry for small molecules, a proprietary platform for the generation and selection of new monoclonal antibodies and the development of other biological drugs and advanced therapies, the validation of new molecular targets, the pharmacological, pharmacokinetic, toxicological and pharmaceutical characterization of new drug candidates; the design and conduct of innovative clinical trials. The company strategy is to develop its own pipeline independently and then seek partnerships with pharmaceutical companies, as well as investing in alliances on innovative projects of other biotech companies or university spin-offs. Contact Federica Girolami (Business Development, Scientific Liaison and Drug Safety Director) Tel. +39 346 4131428 federica.girolami@rottapharmbiotech.com About Agenus Agenus is a clinical-stage immuno-oncology company focused on the discovery and development of therapies that engage the body’s immune system to fight cancer. The Company’s vision is to expand the patient populations benefiting from cancer immunotherapy by pursuing combination approaches that leverage a broad repertoire of antibody therapeutics, adoptive cell therapies (through its affiliate MiNK Therapeutics), adjuvants, and proprietary cancer vaccine platforms. The Company is equipped with a suite of antibody discovery platforms and a state-of-the-art GMP manufacturing facility with the capacity to support clinical programs. Agenus is headquartered in Lexington, MA. For more information, please visit www.agenusbio.com and the Twitter handle @agenus_bio. Information that may be important to investors will be routinely posted on our website and Twitter. Agenus Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding clinical development and regulatory plans and timelines, anticipated corporate milestones, new clinical data and program updates to be presented. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. Contact Agenus Inc. Divya Vasudevan, PhD 781-674-4571 divya.vasudevan@agenusbio.com Agenus Media Relations Kimberly Ha KKH Advisors 917-291-5744 kimberly.ha@kkhadvisors.com

ImmunotherapyClinical StudyVaccine

100 Deals associated with Istituto Nazionale Dei Tumori

100 Translational Medicine associated with Istituto Nazionale Dei Tumori

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Drug(Targets)	Indications	Global Highest Phase

Purvalanol A ( CDK )	Neoplasms More	Preclinical
NU6140 ( CDK x CDK1 x CDK2 )	Neoplasms More	Pending

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