Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced renal cell carcinoma (RCC) (HCRN GU16-260).

Abstract

5006 Background: Nivolumab (nivo) is FDA approved for pts with VEGFR TKI-resistant RCC and the nivo + ipilimumab (nivo/ipi) combination is FDA approved for treatment naïve pts with IMDC intermediate and poor risk RCC. Little information is available on the efficacy and toxicity of nivo monotherapy in treatment naïve RCC or the efficacy of nivo/ipi salvage therapy in pts with tumors resistant to initial nivo monotherapy. Methods: Eligible pts with treatment naïve RCC received nivo 240mg IV q2 wk x 6 doses followed by 360mg IV q3 wk x 4 doses followed by 480 mg q4 wk until progressive disease (PD), toxicity, or completion of 96 wks of treatment (Part A). Pts with PD prior to or stable disease (SD) at 48 wks (pSD) were potentially eligible to receive salvage nivo (3mg/kg) /ipi (1 mg/kg) q3 wk x 4 doses followed by q4 wk nivo maintenance for up to 48 wks (Part B). All pts were required to submit tissue from a metastatic lesion obtained within 12 months (mo) prior to study entry and prior to Part B. Pathology specimens will be analyzed by immunohistochemistry, quantitative immunofluorescence, WES and RNAseq with results linked to clinical outcome. Results: 123 pts with clear cell(cc) RCC were enrolled between 5/2017 and 12/2019 at 12 participating HCRN sites. Median age 65 (range 32-86 years); 72% male. IMDC favorable 30 (25%), intermediate 79 (65%) and poor risk 12 (10%). 22 (18%) had a component of sarcomatoid histology (SARC). 117 pts are currently evaluable for response. RECIST defined ORR was: 34 (29.3%)[CR 5 (4.3%), PR 29 (24.8%)], SD 47 (40.2%), PD 36 (30.7%). ORR by irRECIST was 35%. ORR by IMDC was: favorable 12/29 (41.4%), intermediate/poor 22/87 (25.3%) and for SARC 6/22 (27.3%). Median DOR is 13.8 (10.9, NA) mo. Median PFS is 7.4 (5.5, 10.9) mo. 110 pts remain alive. 60 pts (54 PD, 6 pSD) to date were potentially eligible for salvage nivo/ipi (Part B), but 28 did not enroll due to symptomatic PD (17), grade 3-4 toxicity on nivo (8), other (3). 27 of 32 Part B pts are currently evaluable for efficacy and 30 for toxicity. Best response to nivo/ipi was PR (11%), SD (30%), PD (59%). ORR by irRECIST was 19%. Grade 3-5 Treatment-related AEs (TrAE) were seen in 35/123 (28)% on nivo with 1 death due to respiratory failure. Grade 3-4 TrAE were seen in 10/30 (33%) on nivo/ipi with 0 deaths. Correlative studies are pending. Conclusions: Nivo monotherapy is active in treatment naïve ccRCC across all IMDC groups. Toxicity is consistent with prior nivo studies. Salvage treatment with nivo/ipi after nivo monotherapy was feasible in 53% of pts with PD/pSD, with 11% responding. Clinical trial information: NCT03117309 .

Impact of COVID-19 pandemic on treatment patterns in metastatic clear cell renal cell carcinoma

“…However, only a minority of patients could be rescued by the addition of ipilimumab at the time of disease progression. 32 Hence, compromising drug exposure in the initial treatment phase when an ICI/ICI combination is chosen needs careful balancing.…”

Outcomes With First-Line PD-1/PD-L1 Inhibitor Monotherapy for Metastatic Renal Cell Carcinoma (mRCC): A Multi-Institutional Cohort

“…A different treatment strategy based on individual response to upfront ICI monotherapy is being explored (HCRN GU16-260, OMNIVORE) by allowing treatment interruption to responders while adding other ICI as salvage treatment to non-responders (10,11). Preliminary results in patients with treatment-naïve clear cell mRCC demonstrated some activity of ICI monotherapy with an observed ORR of 29% in the HCRN GU16-260 trial and 12% at 6 months in the OMNIVORE study, respectively.…”

“…In a single-arm phase 2 study (KEYNOTE-427), the PD-1 inhibitor pembrolizumab has shown encouraging antitumor activity in patients with treatment-naïve mRCC with both clear cell and non-clear cell histology (8,9). Two different phase 2 studies (HCRN GU16-260; OMNIVORE) testing nivolumab followed by salvage ipilimumab in patients with clear cell mRCC have also shown clinical activity of nivolumab monotherapy in this setting (10,11).…”

Combination of nivolumab and ipilimumab in the treatment of disseminated renal cell carcinoma. Realities and prospects

“…Исследований эффективности ниволумаба в 1-й линии лечения в монорежиме, а также последовательной иммунотерапии в настоящее время недостаточно. Поэтому представляются интересными предварительные результаты исследования II фазы по изучению эффективности ниволумаба у больных ПКР в 1-й линии терапии, а также по целесообразности добавления ипилимумаба в случае прогрессирования заболевания на фоне монотерапии [10].…”