744P - A phase II study of ACR-368 in patients with ovarian (OvCa) or endometrial carcinoma (EnCa) and prospective validation of OncoSignature patient selection (NCT05548296)

Background

ACR-368 (prexasertib), a potent, selective CHK1/2 inhibitor, has shown durable single-agent activity at RP2D in patients (pts) with OvCa. ACR-368-OncoSignature (BM) is a predictive biomarker test derived from Acrivon Predictive Precision Proteomics (AP3) designed to predict benefit from ACR-368. It has been evaluated in 2 prospectively designed, blinded studies on pretreatment tumor biopsies from past trials demonstrating significant responder enrichment. Furthermore, it -identified EnCa as a new tumor type predicted sensitive to ACR-368 (Murshid et al, AACR-EORTC-NCI 2023) which is now tested in this trial.

Methods

BM was determined on a fresh biopsy in pts with platinum resistant OvCa or EnCa. BM-positive pts (Arm 1) received ACR-368 at RP2D (105 mg/m²) as monotherapy. BM-negative pts (Arm 2) received ACR-368 at RP2D with ultra-low dose of gemcitabine (ULDG; 10 mg/m²). Primary endpoint in Arm 1 was ORR by RECIST 1.1 in a Simon 2-Stage design. Primary endpoint in Arm 2 was safety and RP2D for ULDG, secondary was ORR.

Results

Of 26 efficacy-evaluable patients, all RECIST responses (2 OvCa, 3 EnCa) occurred in Arm 1. No RECIST responses were observed in Arm 2. This provides initial prospective validation of the ACR-368 OncoSignature showing segregation of RECIST responders in the OncoSignature-positive (50% cPR in 10 pts) versus OncoSignature-negative (0% PR in 16 pts) arm (p-value=0.0038). Table: 744P

NOTES: * 1 PR (EnCa) confirmed 1 day after data cut-off. ^ˆ Unenriched ORR in pts with OvCa (N=16) = 12% consistent with past multi-center trial (12.5%; Konstantinopoulos et al, Gyn Oncol, 2022). ^# EnCa is a new tumor type predicted to be sensitive to ACR-368 by AP3-based indication finding not previously evaluated

Adverse events (of 3/8/24; N=21 Arm 1, N= 33 Arm 2) were predominantly transient, mechanism-based, consistent with prior studies (Gr 3/4 anemia, thrombocytopenia, neutropenia and febrile neutropenia observed in Arm1/Arm2 pts were (%/%): 19/15, 10/9, 5/15, and 10/15, respectively).

Conclusions

Initial clinical data from this prospective trial supports the clinical utility of the ACR-368-OncoSignature as a pts selection tool to identify OvCa and EnCa pts sensitive to ACR-368.

Clinical trial identification

NCT05548296.

Editorial acknowledgement

Legal entity responsible for the study

Acrivon Therapeutics.

Funding

Acrivon Therapeutics.

Disclosure

D. Matei: Financial Interests, Personal, Advisory Board: GSK, Eisai; Financial Interests, Personal, Other, Consultant: CVS Health; Financial Interests, Personal, Other, Mentor fee: GOG Foundation; Financial Interests, Institutional, Local PI: Acrivon, Eisai, Shattuck Labs, Moderna; Financial Interests, Institutional, Coordinating PI: Merck. L. Brubaker: Financial Interests, Personal, Advisory Board, Isolated AdBoard participation in October 2022 and May 2024: AstraZeneca. B. Rimmel: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, ImmunoGen, Merck. R.N. Eskander: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, MSD, Clovis Oncology, Myraid, CARIS life sciences, PMV Pharma, Daiichi Sankyo, Regeneron, ImmunoGen, Seagen, AbbVie, Nuvectis Pharma, Faeth Therapeutics, Genentech/Roche; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Institutional, Funding: CanarioBio, Immunognen, Alkermes, Acrivon, ProfoundBio; Non-Financial Interests, Principal Investigator: Gilead, NRG Oncology; Financial Interests, Advisory Role: GOG-Foundation, Clearity Foundation. C. Kyi: Financial Interests, Institutional, Advisory Board: Scenic Biotech; Financial Interests, Personal, Other, Honoraria for educational symposiums: Onclive, Total Health; Financial Interests, Institutional, Coordinating PI: Bristol Myers Squibb, Centessa Pharmaceuticals, Gritstone Bio, Incyte, Eisai, Merus; Financial Interests, Institutional, Steering Committee Member: Acrivon Therapeutics. L. Duska: Financial Interests, Personal, Advisory Board, Scientific advisory board: Aadi Bioscience; Financial Interests, Personal, Royalties, I write expert content for UpToDate: UpToDate; Financial Interests, Personal, Other, I serve on the Editorial Board: British Journal of Obstetrics and Gynecology; Financial Interests, Institutional, Research Grant, Merck has provided funding for investigator initiated trials to my institution: Merck; Non-Financial Interests, Advisory Role, Acted as an expert advisor for: Merck. F. Musa: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca; Financial Interests, Personal, Writing Engagement: Seagen; Financial Interests, Institutional, Local PI: GSK, Allarity Pharmaceuticals, Duality Bio, Aravive, Clovis; Non-Financial Interests, Member of Board of Directors: Society of Gynecologic Oncology. R.L. Coleman: Financial Interests, Personal, Advisory Board: AstraZeneca, Alkermes, ImmunoGen, roche/genentech, GSK, Genmab/Seagen, Epsilogen, Myriad Genetics, Panavance, Profoundbio; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Trial Chair: ImmunoGen; Financial Interests, Personal, Steering Committee Member: Merck, Roche-Genentech, Verastem, AstraZeneca, Gsk; Financial Interests, Personal, Coordinating PI: Karyopharm; Non-Financial Interests, Principal Investigator: abbvie, immunogen, Roche/Genentech, Merck, Genmab; Non-Financial Interests, Project Lead, MyLung Consortium: US Oncology Research. B.M. Slomovitz: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, GSK, Genentech, Merck, ImmunoGen, Novocure, Aadi, Seagen, Incyte; Non-Financial Interests, Member of Board of Directors: GOG Foundation. E.C. Gamelin: Financial Interests, Personal, Full or part-time Employment: Acrivon. J. Cuillerot: Financial Interests, Personal, Full or part-time Employment: Acrivon Therapeutics; Financial Interests, Personal, Stocks/Shares, Stock options: Acrivon Therapeutics; Financial Interests, Personal, Stocks/Shares: BMS, DragonflyTx, SkyHawks. M.M. Phadnis: Financial Interests, Personal, Full or part-time Employment, Senior Vice President, Clinical Operations: Acrivon Therapeutics. B. Guercio: Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Local PI: Genentech, Acrivon; Financial Interests, Institutional, Coordinating PI: Exelixis; Financial Interests, Institutional, Research Grant: Oncocyte; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Non-Financial Interests, Other, Speaker and grant reviewer: Bladder Cancer Advocacy Network; Non-Financial Interests, Member: ASCO, AACR; Other, Invited speaker at conference - travel expenses paid for by Dava Oncology: Dava Oncology; Other, Dinner: Aveo Oncology, Natera, Seagen, Exelixis. P. Konstantinopoulos: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Alkermes, Kadmon, Bristol Myers Squibb, Artios, Schrodinger, Mersana, Novartis, ImmunoGen, Merck KGaA; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Bayer, Merck, Pfizer, GSK, Merck KGaA, Lilly, Bristol Myers Squibb. All other authors have declared no conflicts of interest.