719MO - A phase I/II study of rinatabart sesutecan (Rina-S) in patients with advanced ovarian or endometrial cancer

Background

Rina-S is a novel folate receptor alpha (FRα)-directed ADC with sesutecan, a highly hydrophilic linker and a topoisomerase 1 inhibitor payload.

Methods

PRO1184-001 is an ongoing Phase 1/2 dose escalation (Part A) and expansion/optimization (Part B) study (NCT05579366) in pts with advanced cancers including ovarian (OC) and endometrial (EC). FRα expression is retrospectively tested.

Results

As of 02 April 2024, 53 pts were treated in Part A. Of 32 pts with OC, median number of prior therapies was 5 (1–14); 75% had received bevacizumab; 91% were platinum resistant. Of 11 pts with EC, median number of prior therapies was 3 (1–11); all had received a prior PD-1 inhibitor. Other tumor types were NSCLC, breast, and mesothelioma (n=10 total). In Part B, 35 pts with OC and 13 pts with EC were treated; the median number of prior therapies was 3 (1–4) and 3 (1–7), respectively. Rina-S doses from 60–180 mg/m² were evaluated in Part A. The MTD was 140 mg/m². Doses of 100 and 120 mg/m² were selected for evaluation in Part B. For Part A pts treated at 100 or 120 mg/m² (n=35), the most common (≥20%) treatment-related adverse events (TRAEs) were nausea (n=20, 57%), neutropenia (n=18, 51%), leukopenia (n=16, 46%), anemia (n=15, 43%), thrombocytopenia (n=11, 31%), and vomiting (n=9, 26%); most events were Grade 1/2. The most common (≥10%) ≥ Grade 3 TRAEs were neutropenia (n=12, 34%), anemia (n=9, 26%), leukopenia (n=8, 23%), and thrombocytopenia (n=5, 14%). No ocular toxicity or interstitial lung disease was observed. The emerging safety profile of Rina-S in Part B is consistent with Part A. For Part A OC and EC pts treated at 100 or 120 mg/m², the objective response rate (ORR) was 35% (8/23 pts). In Part B, ORR for OC pts randomized and treated at 100 or 120 mg/m² was 14% (2/14 pts) and 50% (6/12 pts), respectively. As of data cutoff, all confirmed responses are ongoing with a range from 6+ to 30+ wks. Antitumor activity was seen across all FRα expression levels, including FRα undetectable by IHC.

Conclusions

Rina-S was well tolerated at 100 and 120 mg/m², with manageable TRAEs. Promising antitumor activity was observed across a wide range of FRα expression levels. Enrollment for Part B OC pts is complete; dose optimization analysis will be presented.

Clinical trial identification

NCT05579366.

Editorial acknowledgement

Eilidh Williamson PhD, ProfoundBio US Co.

Legal entity responsible for the study

ProfoundBio US Co.

Funding

ProfoundBio US Co.

Disclosure

E.K. Lee: Financial Interests, Personal, Advisory Board: Aadi Bioscience; Financial Interests, Institutional, Coordinating PI, Clinical trial funding: Merck; Financial Interests, Institutional, Local PI: KSQ Therapeutics, Aadi Biosciences, Seagen, Repare Therapeutics, ProfoundBio, OnCusp Therapeutics. O. Yeku: Financial Interests, Personal, Other, Consultant: GIMV NV, TigaTx Inc; Financial Interests, Personal, Advisory Board: hC Bioscience; Financial Interests, Personal, Full or part-time Employment, Associate Editor: NEJM Evidence; Financial Interests, Personal, Other, Patent Pending: MUC16 Directed Antibodies for therapeutic applications; Financial Interests, Personal, Other, Patent pending: Human Artificial Chromosomes for therapeutic applications; Financial Interests, Institutional, Local PI: Ascendis Pharma A/S, Avenge Bio, Inc, Duality Biologics, Immunocore Limited, Merck Sharp & Dohme Corporation, Pionyr Immunotherapeutics Inc, ProfoundBio. I. Winer: Financial Interests, Institutional, Research Funding: Chimerix. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, Olema Pharmaceuticals, Stemline Therapeutics, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Other, Consulting: Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Jefferies LLC, Medical Pharma Services, Tempus Labs, Zentalis Pharmaceuticals; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Dana Farber Cancer Inst, Hutchinson MediPharma, MedImmune, Seagen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, AbbVie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, ImmunoGen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses Pharma, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Artios, BeiGene, Bliss BioPharmaceuticals, Cascadian Therapeutics, Context Therapeutics, Cullinan, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetic Laboratories, Silverback Therapeutics, Stemline Therapeutics. D.L. Richardson: Financial Interests, Personal, Advisory Board: Mersana, AstraZeneca, GSK, ProfoundBio, Eisai, Daiichi Sankyo, ImmunoGen; Financial Interests, Institutional, Research Funding: GSK; Financial Interests, Personal, Steering Committee Member: Karyopharm. G.E. Konecny: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Merck, ImmunoGen; Financial Interests, Institutional, Research Funding: Lilly, Merck; Financial Interests, Personal, Other, Travel, accommodation, expenses: TORL Biotherapeutics. S. Patel: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Certis, Eli Lilly, Jazz, Genentech, Illumina, Merck, Pfizer, Signatera, Tempus; Financial Interests, Institutional, Research Funding: Amgen, AstraZeneca, A2bio, Bristol Myers Squibb, Eli Lilly, Fate Therapeutics, Gilead, Iovance, Merck, Pfizer, Roche/Genentech. A.I. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines, Regeneron, Lilly, Black Diamond Therapeutics, Sanofi; Financial Interests, Personal, Other, Consulting or Advisory Role / Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: NEXT Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Local PI: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Kezar, Revolution Med, Regeneron, Loxo, Alkermes, Medikine, Black Diamond Therapeutics, Nalo Therapeutics, Scorpion Therapeutics, Arrivent Biopharma. E. Kavalerchik, Z. Chen, E. Song: Financial Interests, Personal, Full or part-time Employment: ProfoundBio; Financial Interests, Personal, Stocks/Shares: ProfoundBio. All other authors have declared no conflicts of interest.