In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 6_suppl ( 2021-02-20), p. 334-334
Abstract:
334 Background: Immune therapy combinations are now standard first-line therapy for pts with mccRCC. Cabo modulates key components of the immune system such as decreasing regulatory T-cells and increasing T-effector cell populations and is approved for treatment of mRCC. We hypothesize that Ave + Cabo will be safe and show clinical activity in mccRCC. Methods: Prospective phase I clinical trial using a 3+3 design with three planned dose cohorts: Cabo 20mg/day, 40mg/day and 60mg/day + Ave (10mg/kg q2weeks) in each arm. The primary endpoint was safety and identification of the recommended phase II dose (RP2D). Key secondary endpoints included objective response rate (ORR) and radiographic progression free survival (PFS). No dose modifications were allowed for Ave but dose delays were permitted. Dose reductions were allowed for Cabo. There were an additional 3 patients included in the final dose cohort as a confirmation of the RP2D. RECIST 1.1 was used to determine ORR. Treatment beyond progression was allowed. Results: Twelve patients with newly diagnosed mccRCC were enrolled from 08/2018 through 03/2020. Three patients were enrolled into the 20 and 40mg cohorts each, six patients enrolled in the 60mg cohort. IMDC risk: favorable 4 patients, intermediate 6 patients, poor 2 patients. No dose limiting toxicities were observed in any cohort. Only one SAE related to study treatment was observed, thromboembolism, after the DLT period. Immune related adverse events (irAE) occurred in six patients (50%) and included hypothyroidism, colitis, nephritis, allergic rhinitis and rash. Six patients required dose reductions of cabozantinib after the DLT period: one in the 40mg cohort and five in 60mg cohort, most frequently due to oral mucositis and hand foot syndrome. One patient discontinued Ave due to irAE (nephritis). No patients discontinued Cabo due to toxicity. The ORR was 33% (all PR). The clinical benefit rate (CR+PR+SD) was ~ 92%. One patient experienced PD on the first scan and then continued on the protocol treatment without further progression at the time of this report (follow up to date ~ 7 months). Seven of 12 pts are still on protocol treatment. Conclusions: Ave + Cabo in mccRCC is safe and preliminarily efficacious. Even though the DLT was not met in any of the cohorts, based on dose reduction required in 5 of 6 pts in the Cabo 60 mg cohort after the DLT period, the recommended RP2D dose for the combination is Cabo 40mg/day and Ave 10mg/kg q2 weeks. Safety and efficacy data will be elaborated in the meeting. * NA & BLM: equal contribution Clinical trial information: NCT03200587 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2021.39.6_suppl.334
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2021
detail.hit.zdb_id:
2005181-5
