118O - Definitive results for NSCLC and Bladder cancer cohorts in the phase 2a trial of visugromab (CTL-002) in advanced/metastatic anti-PD/PD-L1 relapsed/refractory solid tumors (GDFATHER-trial)

Background

GDF-15 plays a critical role in feto-maternal tolerance and cancer-mediated immunosuppression [NatComm14,4253;2023]. Here we report definitive results for NSCLC and bladder cancer cohorts of the phase 1/2a trial of the GDF-15 neutralizing antibody visugromab (CTL-002) in combination with nivolumab for treatment of patients that were relapsed/refractory to anti-PD1/-PD-L1 therapy and had exhausted standard-of-care.

Methods

Pts received visugromab 10 mg/kg Q2W + nivolumab 240 mg Q2W, mostly in 3^rd-4^th line of treatment. The primary endpoint was objective response rate (ORR). All patients were by strict criteria either (1) primary refractory to or (2) relapsed on continued CPI therapy after initial response, and a required minimum of 12 wks continuous anti-PD1/-PD-L1 exposure.

Results

114 patients in various cohorts initiated treatment in ph2a. The vast majority of treatment-emergent adverse events (TEAE) reported were mild to moderate, with just 3.7% of patients experiencing TEAE Grade > 3. Regarding antitumoral efficacy, in NSCLC and bladder cancer (N = 27 pts, each) confirmed RECIST response rates of 15% were observed in this heavily pretreated, advanced/metastatic and checkpoint inhibitor relapsed/refractory last-line population. Responses were seen mainly in PD-L1+ tumors , and remarkably, in the bladder cancer cohort all patients with TPS ≥ 5 in baseline tumor biopsy experienced a PR or CR. Depth and durability of responses was significant, with several responses ongoing at 1yr and beyond, despite all patients being in last-line situation.

Conclusions

Visugromab in combination with nivolumab demonstrated excellent safety and promising antitumoral activity in last-line, and by stringent criteria anti-PD1/PD-L1 relapsed/refractory solid tumor patients. Confirmed partial and complete responses with significant durability up to and beyond 1 year were observed. Biomarker analyses suggest that visugromab can reinvigorate, enhance and deepen response to checkpoint inhibitors mainly in PD-L1+ patients even after documented prior progression on a seamlessly administered checkpoint inhibitor, being relapsed/refractory to it.

Clinical trial identification

NCT04725474.

Legal entity responsible for the study

CatalYm GmbH.

Funding

CatalYm GmbH.

Disclosure

I. Melero: Financial Interests, Personal, Advisory Board: Alligator Bioscience, AstraZeneca, BMS, BioLineRx, Boehringer Ingelheim, Boston Pharma, CRISPR Therapeutics, CatalYm GmbH, Curon BIopharmaceutical, EMD Serono, Genentech, Hookipa Pharma, Genmab, Gossamer Bio, Highlight Therapeutics, HotSpot Therapeutics, Inc., Monopteros Therapeutics, ImmuneSensor Therapeutics, Inc., Janssen, MSD, Noxxon Pharma AG, Numab, Sanofi, Roche, Senti Biosciences, Servier; Financial Interests, Personal, Other, Consultant: Pharma Mar; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Roche, BMS, Genmab, Alligator. G.A. De Velasco Oria: Financial Interests, Personal, Advisory Board: Pfizer, Astellas, BMS, MSD, Ipsen, Bayer, AstraZeneca, Eisai; Financial Interests, Personal, Invited Speaker: Pfizer, Astellas, BMS, MSD, Roche, Ipsen, Merck, Novartis, Janssen, Bayer; Financial Interests, Institutional, Research Grant: Roche. E. Ramelyte: Financial Interests, Personal, Advisory Board: Sanofi, BMS, Pierre Fabre, Leo Pharma; Financial Interests, Personal, Invited Speaker: Sanofi, BMS, Novartis; Financial Interests, Personal, Writing Engagement: Sanofi; Financial Interests, Personal, Other, Travel grant: Sanofi, Galderma; Financial Interests, Personal, Other, Travel Grant: Pfizer; Financial Interests, Institutional, Other, Project related research funding: Amgen; Financial Interests, Personal, Royalties: Uptodate inc; Financial Interests, Personal and Institutional, Coordinating PI: Sanofi; Non-Financial Interests, Personal, Member: ASCO. M. Joerger: Financial Interests, Institutional, Coordinating PI, Clinical study activity: Basilea, Bayer, BMS, Immunophotonics, MSD, Novartis, Roche; Financial Interests, Institutional, Other, Clinical study activity: DaiichySankyo; Financial Interests, Institutional, Local PI, Clinical study activity: Innomedica; Non-Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Basilea, Bayer, BMS, Debiopharm, MSD, Roche, Sanofi. J. Martin-Liberal: Financial Interests, Personal, Invited Speaker: Astellas, Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Pierre Fabre, Roche, Sanofi, Highlight Therapeutics; Financial Interests, Personal, Other, Travel grant: Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Ipsen. D. König: Financial Interests, Institutional, Advisory Board: AstraZeneca, Amgen, Sanofi, MSD, Merck; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Roche, Amgen, Sanofi. E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Amunix, Anaveon, AstraZeneca, BMS, Janssen, MonTa, MSD, Nanobiotix, Nouscom, Novartis, Servier, TargImmune, T-knife, Chugai, Elevation Oncology, Ellipses Pharmacy, SyneosHealth, Genmab, Diaccurate; Financial Interests, Personal, Invited Speaker: OncoDNA, PharmaMar, Roche/Genentech; Financial Interests, Personal, Full or part-time Employment, Director, Clinical Research: HM Hospitales Group; Financial Interests, Personal, Full or part-time Employment, Medical Oncologist. Clinical Investigator. Director, Clinical Research: START Madrid - CIOCC (Centro Integral Oncológico Clara Campal); Financial Interests, Personal, Member of Board of Directors, External Independent member of Board of Directors: PharmaMar; Financial Interests, Personal, Ownership Interest: START, Oncoart Associated; Financial Interests, Personal, Steering Committee Member, Member of Data Monitoring Committee: BeiGene, Sanofi, Merus; Financial Interests, Personal, Steering Committee Member: Novartis; Non-Financial Interests, Personal, Other, Non-for-profit Foundation. President and co-founder: INTHEOS (Investigational Therapeutics in Oncological Sciences) non-for-profit Foundation; Non-Financial Interests, Personal, Advisory Role: PsiOxus; Non-Financial Interests, Personal, Other, Chair of the Independent Data Monitoring Committee: EORTC IDMC; Non-Financial Interests, Personal, Member of Board of Directors, Non-for-profit Foundation, trustee member: Non-for-profit Foundation PharmaMar; Non-Financial Interests, Personal, Advisory Role, Non-for-profit foundation: CRIS Cancer Foundation, non-for-profit ; Non-Financial Interests, Personal, Member: ASCO, ESMO, SEOM, EORTC. E. Garralda: Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte; Financial Interests, Personal, Invited Speaker: MSD, Lilly, Roche, Thermo Fisher, Novartis, SeaGen; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: BeiGene, Janssen. R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaviVAX SA, Simcere, touchIME, T3 Pharma, Pfizer. J. Esteban Villarrubia: Financial Interests, Personal, Invited Speaker: BMS, Pfizer, Merck, Eisai, Pfizer. M. Goebeler: Financial Interests, Personal, Other: BMS, AstraZeneca, Janssen-Cilag, Novartis, Gemoab. P. Fettes: Financial Interests, Personal, Full or part-time Employment: CatalYm; Financial Interests, Personal, Stocks/Shares: CureVac. K. Klar, E. Leo: Financial Interests, Personal, Full or part-time Employment: CatalYm GmbH. All other authors have declared no conflicts of interest.