716P - Optimizing ipilimumab in metastatic renal cell carcinoma: SAKK 07/17 study

Background

Nivolumab (Nivo) + ipilimumab (Ipi) is an approved 1^st line treatment for mRCC patients (pts) with an intermediate or poor risk score (IMDC). The CheckMate 214 (CM-214) study showed superior outcomes for Nivo + Ipi compared to sunitinib in these pts. Whether the CM-214 induction with 4 cycles of Ipi (1mg/kg/q3w) and Nivo (3mg/kg/q3w) followed by a maintenance treatment of Nivo (3mg/kg/q2w) is the optimal scheme regarding efficacy and safety remains to be determined. SAKK 07/17 study aims to reduce AEs by individualizing Ipilimumab application while preserving overall efficacy and outcome.

Methods

SAKK 07/17 is an ongoing prospective single-stage single-arm multicenter phase II trial in Switzerland with an enrolment goal of 74 pts. Pts start treatment with Nivo (240mg q2w until wk20, 480 mg q4w thereafter). After 2 wks Ipi 1mg/kg/q6w is introduced. As soon as a radiographic complete response (CR) or partial response (PR) is observed, Ipi is stopped and Nivo continued for a maximum of 2 years. The primary endpoint is objective response rate (ORR) per RECIST with a rate of ≤ 20% regarded as unpromising and ≥ 40% as promising activity. Secondary endpoints include PFS, DOR, TTF, OS, AEs and a strong translational research with serial biopsies is an integral part of the trial. In the first cohort 32 pts with mRCC of any IMDC risk entered the study for 1^st or 2^nd line (post-TKI) treatment between 12/2017 and 02/2019.

Results

Of the 32 pts, 25 pts were treated in 1^st and 7 pts in 2^nd line. Median age was 69 y (range 48-86). According to IMDC risk score 12.5% had favorable, 53% intermediate and 34.5% poor risk. At a median follow-up of 18.3 months (mo) the ORR was 53.1% (CR=3.1%, PR=50%, SD=21.9%, PD=18.8 %, NA=6.3%) (ORR 90% CI 39% - 68%, p < 0.001 (one-sided)). The frequency of AEs and SAEs was comparable to Nivo3 q2w/ Ipi1qx4 4w. Elevated CRP, IL-6 and sGOLPH2 were factors significantly associated with higher IMDC scores and support a prognostic appraisal.

Conclusions

SAKK 07/17 is the first study to assess the impact of reducing Ipi in the combination treatment of mRCC. Regarding ORR the strategy is promising and does not appear to be inferior to CM-214. Preliminary data suggest an association of CRP, IL-6 and sGOLPH2 and prognosis. Further analysis is ongoing regarding endpoints, depth and duration of response.

Clinical trial identification

NCT03297593.

Editorial acknowledgement

Legal entity responsible for the study

The Swiss Group for Clinical Cancer Research (SAKK).

Funding

Bristol-Myers Squibb.

Disclosure

F. Stenner-Liewen: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: MSD; Honoraria (institution), Advisory/Consultancy: Merck. R. Cathomas: Advisory/Consultancy: Roche; Advisory/Consultancy: Astellas; Advisory/Consultancy: Janssen; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pfizer; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer; Advisory/Consultancy: AstraZeneca; Honoraria (institution): Debiopharm; Honoraria (institution): Astellas; Honoraria (institution): BMS; Travel/Accommodation/Expenses: AstraZeneca. C.A. Rothermundt: Research grant/Funding (institution): Astellas; Honoraria (self): Merck (CH) AG; Advisory/Consultancy: Pfizer; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche. A. Patrikidou: Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: BMS. D. Zihler: Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre-Fabre; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: Amgen. M. Küng: Advisory/Consultancy: MSD. D. Berthold: Honoraria (institution), Advisory/Consultancy: BMS; Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: MSD; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Novartis. H. Läubli: Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb (BMS); Honoraria (institution), Travel/Accommodation/Expenses: MSD; Research grant/Funding (institution): Palleon Pharma; Honoraria (institution), Travel/Accommodation/Expenses: Merck (CH) AG. All other authors have declared no conflicts of interest.