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Poster session 01

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)

Date

14 Sep 2024

Session

Poster session 01

Topics

Cancer Biology;  Targeted Therapy;  Cancer Research

Tumour Site

Ovarian Cancer;  Endometrial Cancer

Presenters

Jung-Min Lee

Citation

Annals of Oncology (2024) 35 (suppl_2): S544-S595. 10.1016/annonc/annonc1592

Authors

J. Lee1, S. MacLaughlan2, D. Matei3, M. Song4, L. Brubaker5, B. Rimmel6, R.N. Eskander7, C. Kyi8, H. Williams9, L. Duska10, F. Musa11, R.L. Coleman12, B.M. Slomovitz13, E.C. Gamelin14, J. Cuillerot15, M.M. Phadnis16, B. Guercio17, S. Crafton18, P. Konstantinopoulos19

Author affiliations

  • 1 Women’s Malignancies Branch, National Cancer Institute, 20892 - Bethesda/US
  • 2 Medical Oncology, University of Illinois Cancer Center, 60612 - Chicago/US
  • 3 Medicine, Northwestern University Feinberg School of Medicine, 60611 - Chicago/US
  • 4 Medical Oncology, City of Hope Comprehensive Cancer Center, 91010 - Duarte/US
  • 5 Medical Oncology, UCHealth Cancer Care - Anschutz Medical Campus - University of Colorado Cancer Center, 80045 - Aurora/US
  • 6 Medical Oncology, Cedars-Sinai Medical Center, 90048 - Los Angeles/US
  • 7 Obstetrics, Gynecology And Reproductive Sciences, University of California San Diego - UCSD, 92093 - La Jolla/US
  • 8 Gynecologic Oncology, MSKCC - Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 9 Medical Oncology, UAMS - University of Arkansas for Medical Sciences, 72205 - Little Rock/US
  • 10 Medical Oncology, The University of Virginia, Charlottesville/US
  • 11 Gynecologic Oncology, Swedish Cancer Institute - Medical Oncology - First Hill, 98104 - Seattle/US
  • 12 Gynecologic Oncology Department, The US Oncology Network, 77380 - The Woodlands/US
  • 13 Gynecology-oncology Department, Mount Sinai Comprehensive Cancer Center, 33140 - Miami Beach/US
  • 14 Chief Medical Officer, Acrivon Therapeutics, Inc., 02472 - Watertown/US
  • 15 Clinical Research, ACRIVON, 02472 - Watertown/US
  • 16 Clinical Operations, Acrivon Therapeutics, Inc., 02472 - Watertown/US
  • 17 Medical Oncology, URMC - University of Rochester Medical Center, 14615 - Rochester/US
  • 18 Medical Oncology, West Penn Hospital, 15224 - Pittsburgh/US
  • 19 Medical Oncology, Dana Farber Cancer Institute, 02215 - Boston/US

Resources

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Abstract 744P

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

Data cut-off April 1, 2024 OncoSignature Positive (N=10) OncoSignature Negative (N=16)
Ovarian Endometrial Ovarian Endometrial
Confirmed PR 2 3* 0 0
SD 2 1 6 2
PD 1 1 5 3
Total 5 5 11 5
ORR (%) (95% CI) 40ˆ (12%, 77%) 60# (23%, 88%) 0ˆ 0#
ORR (%) GYN Total (95% CI) 50 (23%, 76%) 0

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.

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