Abstract 1742P
Background
Poly-ADP ribose polymerase inhibitors (PARPi) have immunomodulatory properties, notably by activating the cGAS/STING innate immune pathway and by inducing PD-L1 expression. The Gustave Roussy-sponsored academic Phase 2 basket study ARIANES (EudraCT 2018-001744-62) evaluated the efficacy of the PARPi rucaparib (R) in combination with the anti-PD-L1 atezolizumab (A) in unselected, platinum-sensitive, or molecularly-selected pts. Here we report results from the platinum-sensitive mUC and unselected mCRPC cohorts.
Methods
Pts with mCRPC had to have received ≥2 androgen receptor pathway inhibitor (ARPi). Prior PARPi was not allowed. Pts received a 3-week run-in of R (600mg BID), prior adding A (1.2g q3wks) until progression. Primary endpoint was overall response rate (ORR) at 12 wks, with 3/16 (mUC) and 9/24 (mCRPC) pt responses required to declare A + R worth further exploration. Secondary endpoints were disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) according to RECIST, iRECIST and PCWG-3, overall survival (OS), safety and biomarker analysis.
Results
16 mUC and 24 mCRPC pts were enrolled. No pt received prior anti-P-(L)1 therapy. Twenty (83%) and 22 (92%) mCRPC pts received ARPI and chemotherapy, respectively; 19 had bone metastases. Two mUC and 2 mCRPC pts achieved response at 12 wks. The table below summarizes other efficacy endpoints. The most common ≥Grade 3 adverse events were anemia (25%), fatigue (13%), nausea/vomiting (10%). No new safety signal was detected. Table: 1742P
| Median age (IQR) | Median # of prior lines (IQR) | # of pts with RECIST measurable disease | 12-wk ORR (95% CI) | 12-wk iORR (95% CI) | DCR (95% CI) | DOR (mo) (95% CI) | mPFS (mo) (95% CI) | |
| mUC (n=16) | 67 (56; 73) | 1 (1; 2) | 13 | 12.5% [1.6;38.3] | 12.5% [1.6;38.3] | 37.5% [15.2;64.6] | 12.4 [5.5; 19.3] | 2.7 [1.3; 4.1] |
| mCRPC (n=24) | 66 (62; 74) | 4 (3; 4) | 20 | 8.3% [1.0;27.0] | 8.3% [1.0;27.0] | 41.7% [22.1;63.4] | 2.8 [1.3; ] | 4.1 [2.7; 5.3] |
IQR: interquartile range
Conclusions
Tumor responses and disease control were observed in both cohorts. Although the 12-wk ORR was below the pre-specified threshold, the 12-wk DCR of 38% and 42% in the mUC and mCRPC cohorts, respectively, shows activity in this unselected patient population. Retrospective correlation with the tumor molecular profile is warranted.
Clinical trial identification
EudraCT 2018-001744-62; NCT04276376.
Editorial acknowledgement
Legal entity responsible for the study
Institut Gustave Roussy.
Funding
Roche and Clovis Oncology.
Disclosure
P. Martin Romano: Financial Interests, Institutional, Principal Investigator, and co-investigator: for AbbVie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd., Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, BicycleTx Ltd., Blueprint. G. Roubaud: Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Personal, Advisory Board: Astellas, Bayer, Sanofi, Janssen, AstraZeneca, and Pfizer. P. Lavaud: Financial Interests, Personal, Advisory Board: Astellas, AZ, Sanofi, Janssen; Financial Interests, Personal, Other, Travel accommodation: Ipsen, Janssen, Astellas, Pfizer. G. Buzzatti: Financial Interests, Personal, Advisory Board: Lilly, Novartis, Pfizer. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion. S. Postel-Vinay: Financial Interests, Institutional, Research Grant: AstraZeneca; Roche IMCore; Financial Interests, Institutional, Principal Investigator, or co-investigator: AbbVie, Adaptimmune, Adlai Nortye USA Inc., Aduro Biotech, Agios Pharmaceuticals, Amgen, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd., Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, BicycleTx Ltd., Blueprint Medi. All other authors have declared no conflicts of interest.