Abstract 1454P
Background
N + Ipi is approved for 1st line treatment in advanced RCC patients (pts) with an intermediate or poor risk score (IMDC). The CheckMate 214 study (CM-214) with 4 cycles of Ipi (1mg/kg/q3w ) and N (3mg/kg/q2w) showed superior outcomes for N+Ipi compared to Sunitinib. SAKK 07/17 (CM-980) is a prospective single-stage single-arm multicenter phase II trial with 10 swiss centres and a total of 74 pts examining the treatment-related adverse events (TRAEs) by individualizing Ipi applications while preserving overall efficacy and outcome.
Methods
74 pts with metastatic clear cell RCC and all IMDC risks entered the study for 1st or 2nd line (after TKI) therapy from 12-2017 to 6-2019. 68 pts were evaluable for analysis. In cohort 1 (C1) pts. started treatment with N (240mg q2w until w20 and 480 mg q4w thereafter). After 2 weeks Ipi 1mg/kg/q6w was introduced. As soon as a radiographic complete or partial response (CR, PR) was observed, Ipi was stopped and N was continued until progression or a maximum of 2 years. In cohort 2 (C2) (pts 33-74) Ipi-rechallenge was allowed. The primary endpoint was investigator assessed objective response rate (ORR) per RECIST with a H0 ORR of 20% (one-sided significance level 0.05). Secondary endpoints included PFS, DOR, TTF, OS, AEs and TRAEs.
Results
From 68 pts, 61 received N+Ipi in 1st and 7 in 2nd line. Median age was 66 y (range 42-86). The median Ipi dose per patient was 2.5 (range 1-16). At a median follow-up of 42.5 (C1) and 20.4 (C2) months (mo) the pooled ORR was 42.6% (90% CI 32.4%-53.3%, p < 0.001 (one-sided)). The frequency of Grade ≥3 AEs and TRAEs were 77.3% and 47%, the median PFS was 8.7 mo (95% CI 6.0-11.8), median OS was 41 mo (95% CI 38.2-n.r.).
Conclusions
SAKK 07/17 was the first study to examine and report the impact of reducing Ipi in the treatment of mRCC. Here we report ORR, TRAE, PFS, OS. Despite, longer intervals of Ipi q6w and an overall lower dose of Ipi, a 47% rate of Grade 3/4 TRAE was observed. The frequency of TRAE (47%) in SAKK 07/17 was similar to those in CM-214 (46%). With 42.6% ORR, SAKK07/17 is comparable to ORR of the CM-214 trial (42.1, 39.1 and 28.8% according to risk group). Despite a similar safety profile and similar ORR, a shorter PFS and OS compared to CM-214 does not encourage routine Ipi delays or reductions.
Clinical trial identification
NCT03297593.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
BMS.
Disclosure
F. Stenner-Liewen: Financial Interests, Institutional, Advisory Board: Roche, BMS, MSD, Pfizer, IPSEN; Financial Interests, Institutional, Invited Speaker, Translational research support within a study: BMS; Non-Financial Interests, Principal Investigator, Trial PI: BMS. R. Cathomas: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Bayer, MSD, Roche, Sanofi, Astellas, Ipsen, Merck, Pfizer, Debiopharm; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Astellas. C.A. Rothermundt: Financial Interests, Institutional, Advisory Board: BMS, Roche, MSD, Merck, Novartis, Pfizer. J. Beyer: Financial Interests, Personal, Other, Co-Sponsored Educational Event: Astellas; Financial Interests, Personal, Other, Co-Sponsored Educational Event: Bayer; Financial Interests, Personal, Other, Co-Sponsored Educational Event: Janssen; Financial Interests, Personal, Other, Co-Sponsored Educational Event: Ipsen; Financial Interests, Personal, Other, Co-Sponsored Educational Event: Merck; Financial Interests, Personal, Other, Co-Sponsored Educational Event: Pfizer; Financial Interests, Personal, Other, Co-Sponsored Educational Event: Roche; Financial Interests, Personal, Other, Co-Sponsored Educational Event: AstraZeneca; Financial Interests, Personal, Other, Co-Sponsored Educational Event: Sanofi; Financial Interests, Personal, Other, Co-Sponsored Educational Event: Novartis; Financial Interests, Personal, Other, Co-Sponsored Educational Event: Bristol Myers Squibb; Financial Interests, Personal, Other, Co-Sponsored Educational Event: Amgen; Financial Interests, Personal, Other, Co-Sponsored Educational Event: Lilly. M. Kueng: Financial Interests, Personal, Advisory Board: BMS, MSD. A. Lorch: Financial Interests, Personal, Advisory Board: BMS, Merck, Pfizer, MSD, Astellas, Janssen, Roche, Ipsen, Bayer; Non-Financial Interests, Principal Investigator: PI in several phase II and III trials in the field of urooncology; Non-Financial Interests, Member: ASCO, DGHO, DKG, AIO, EAU, MAGIC, Swiss Ethics Committee, SAKK, SAKK Scientific Committee, EAU Guideline Bladder Cancer, Onkopedia Guideline Testis Cancer, Bladder cancer, German S3 Guidelines Testis Cancer, Wilsede School of Oncology; Non-Financial Interests, Other, Invited advanced training talks: SAMO Switzerland. D.R. Berthold: Financial Interests, Institutional, Invited Speaker: Astellas, Janssen; Financial Interests, Institutional, Advisory Board: MSD, Ipsen, Bayer, BMS, Roche. H. Läubli: Financial Interests, Institutional, Advisory Board: BMS, MSD. All other authors have declared no conflicts of interest.