Rana R. McKay, MD UC SD Health discusses ASCO 2020 abstract entitled Optimized management of nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma (RCC): A response-based phase II study (OMNIVORE)
Context:
For advanced RCC, Nivo + Ipi is a proven first-line treatment (tx). We hypothesized that not all patients (pts) would need to have CTLA-4 blockade applied. In addition, Nivo’s optimum maintenance time in response pts is not known. In this phase II response-adaptive trial, we investigate the sequential addition of 2 doses of Ipi in response pts (NCT03203473) to induce response in Nivo non-responders (NR) and duration of Nivo.
Approaches:
We have enrolled pts with advanced RCC without previous exposure to the checkpoint inhibitor. All pts received Nivo alone within 6 months (mos) of tx, with subsequent arm allocation based on RECISTv1.1 response. Nivo was discontinued and observed (Arm A) pts with a reported partial response (PR) or full response (CR) within 6 months (mos). Arm A pts reinitiated Nivo if progressive disease (PD) developed; when PD continued or recurred, Ipi was applied to Nivo. Pts with a stable disease (SD) or PD have obtained 2 doses of Ipi (Arm B) after no more than 6 mos of Nivo alone. The primary endpoints were the 1-year (yr) PR / CR proportion after Nivo discontinuation (Arm A) and the proportion of Nivo NR converting to PR / CR after Ipi (Arm B) addition.
Reviews:
83 pts initiated tx, of which 99% had ECOG 0-1, 96% clear cell RCC, 51% tx-naïve and 69% intermediate / poor IMDC risk. There was a median follow-up of 17.0 mos. The arm was not allocated 15 pts [7 withdrawals for PD, 7 withdrawals for toxicity, 1 only on tx with unconfirmed PR (uPR)]. At 6 mos, Nivo induction resulted in a verified PR at 11% of pts (n=9/83): 12% (n=5/42) tx-naïve, 10% (4/41) prior tx, 8% (n=1/13) favorable risk, 11% (n=8/70) intermediate / poor risk (Table). Arm A was assigned 11 pts (13 percent: 9 PR, 1 uPR, 1 SD), of which 5 (45 percent, 90 percent CI 20-73 percent) remained off Nivo at 1 year old. 2 pts converted to a PR (4 percent, 90 percent CI 1-11 percent) of 57 pts (69 percent) allocated to Arm B, both of which had previous tx and PD as the best response to Nivo alone. Adverse events associated with grade 3-4 treatment (TrAE) occurred in 7 percent (n=6/83) on Nivo induction and in 23 percent (n=13/57) on Arm B (Nivo + Ipi).
Conclusions Therein:
At present, due to the lack of CR and low PR / CR conversion rate (4 percent), we do not suggest a Nivo strategy followed by response-based Ipi addition. Although a subset of pts treated with Nivo alone can sustain a lasting response off tx at 1-yr, it is currently not recommendable to discontinue early Nivo in the absence of toxicity. Research into biomarkers to direct tx continues. Details on clinical trials: NCT03203473.