34O - ROCSAN: A multicentric randomized phase II/III evaluating dostarlimab in combination with niraparib versus niraparib alone compared to chemotherapy in the treatment of endometrial/ovarian carcinosarcoma after at least one line of platinum-based chemotherapy – Preliminary results

Background

Carcinosarcomas (CS) are rare and highly aggressive gynecological carcinomas with poor outcome. The median Progression-Free-Survival (PFS) in relapse after platinum-based chemotherapies (CT) is less than 4 months. CS were excluded from Keynote755 trial. Since CS show high DNA damage response activity and potentially a high tumor mutational load resulting in neo-antigens, a synergy between PARPi and anti-PD1 is expected.

Methods

This is an open-label (NCT03651206) study with a two-stage design. In step 1, patients (pts) were randomized (2:2:1) to receive either niraparib (N), niraparib and dostarlimab (ND) or chemotherapy (CT). Randomization was stratified by number of previous CT lines, FIGO stage, localization, and performance status. The primary objective was to select the best experimental strategy between N and ND using Response Rate (RR) at 16 weeks (RECIST1.1). Secondary endpoints included best Objective RR, disease control rate (DCR), safety, OS & QoL. After an interim analysis at the end of phase II, data will be reviewed by an Independent Data Monitoring Committee, and eventually allow the enrolment in subsequent phase III (part 2).

Results

64 pts with recurrent or progressing endometrial or ovarian CS after at least one line of platinum-based CT were randomized in the phase II (N=26, ND=25, CT=13). Median age was 70 years (range 34-84). The 16w-RR was 3.8%, 12.0% and 15.4% respectively. The ORR was 3.8%, 20% and 15.4% and the 8w-DCR was 26.9%, 52% and 30.8% in arm N, ND and CT, respectively. With a median follow-up of 11.2 months, median PFS (months) was 2.0 (95%CI, 1.9-2.2), 2.7 (95%CI, 1.9-3.7), 1.9 (95%CI, 1.7-3.6) and median OS (months) was 6.7 (95%CI, 3.8-9.6), 6.3 (95%CI, 3.9-12.4), 4.5 (95%CI, 3.0-NE) in arm N, ND and CT respectively. %AE grade >3 were 69.2%, 68% and 69.2% respectively.

Conclusions

ROCSAN step 1 did not met primary endpoint for 16W RR (> 20%), however the DCR, median OS and safety suggest some benefice for ND compared to CT in this very rare and poor prognostic population.

Clinical trial identification

NCT03651206, EudraCT 2019-002662-12.

Legal entity responsible for the study

ARCAGY-GINECO.

Funding

ARCAGY-GINECO and GSK.

Disclosure

I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, Sutro, BMS, Daiichi Sankyo, Immunogen, Seagen, PMVpharma; Financial Interests, Institutional, Other, Colibri translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Personal, Principal Investigator: PAOLA1; Non-Financial Interests, Personal, Other, President: GINECO. A. Bellesoeur: Financial Interests, Institutional, Invited Speaker: LEopharma, GSK, General Electric; Non-Financial Interests, Personal, Member, health democraty committee: Institut national du Cancer. M. Fabbro: Financial Interests, Personal, Advisory Role: GSK. H. Vanacker: Financial Interests, Personal, Principal Investigator: Eli Lilly. F. Bigot: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Sanofi, MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD; Other, Personal, Other, Travel / accommodation / congress: MSD. A. Angelergues: Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca. L. Eberst: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, MSD. C. Lebreton: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Expert Testimony: GSK, MSD, Eisai, Clovis oncology. C. Lefeuvre-Plesse: Financial Interests, Personal, Advisory Board: Roche, Pfizer, Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Clovis; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Personal, Member: societe française de senologie et de pathologie mammaire; Other, Personal, Other, support financier pour participation à des congrès: Novartis, Roche, Eisai, Pfizer, Pierre Fabre, Daiichi Sankyo, AstraZeneca, Amgen, Clovis. C. Deldycke: Financial Interests, Personal, Invited Speaker: Sanofi, Amgen, Takeda, AstraZeneca, BMS/Roche. M. Mouret-Reynier: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai Pharma, Eisai, GSK, MSD, Lilly France, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi Aventis, Gilead. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape, Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK, AstraZeneca, Clovis, Ability Pharma, MSD, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Other, consultancy: OWKIN; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO, Sanofi, AstraZeneca; Financial Interests, Institutional, Funding, CI clinical trial: AstraZeneca; Financial Interests, Institutional, Research Grant, Int CI clinical trial: OSE immuno; Financial Interests, Institutional, Funding, PI clinical trial: Agenus, BMS, Iovance, GSK; Financial Interests, Institutional, Funding, PI 5 clinical trials: Roche; Financial Interests, Institutional, Funding, PI 2 clinical trials: AstraZeneca; Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee: MSD; Non-Financial Interests, Institutional, Other, Academic research project: Owkin, LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer; Non-Financial Interests, Personal, Member: GCIG. All other authors have declared no conflicts of interest.