LBA73 - Tivozanib–nivolumab vs tivozanib monotherapy in patients with renal cell carcinoma (RCC) following 1 or 2 prior therapies including an immune checkpoint inhibitor (ICI): Results of the phase III TiNivo-2 study

Background

The selective VEGFR TKI tivozanib has demonstrated single agent activity following VEGFR TKI and ICI, and in combination with ICI. TiNivo-2 was designed to test the combination of the PD-1 inhibitor nivolumab and tivozanib vs tivozanib monotherapy following tumor progression on prior ICI-based therapy.

Methods

TiNivo-2 enrolled pts with advanced clear-cell RCC who had 1–2 prior lines of therapy, including an ICI. Pts were randomized to receive tivozanib (0.89 mg) plus nivolumab or tivozanib alone (1.34 mg). The primary endpoint was PFS by independent radiology review (IRR); the key secondary endpoint was OS, other secondary endpoints included investigator-assessed PFS, ORR, DoR, and safety/tolerability. A sample size of 343 pts with 220 events provided ≥80% power to detect a 50% improvement in PFS, 12 m vs 8 m, assessed by IRR.

Results

343 pts were randomized to tivozanib–nivolumab (n=171) or tivozanib (n=172). Baseline characteristics were well balanced. With a median IRR-assessed PFS of 5.7 m for tivozanib–nivolumab and 7.4 m for tivozanib (HR 1.10 [95% CI 0.82. 1.43]), the study did not meet its primary endpoint. Among those with ICI as immediate prior therapy (n=244), mPFS was 7.4 m (95% CI, 5·55-9·56) with tivozanib–nivolumab and 9.2 m (95% CI, 7·43-9·99) with tivozanib. Data for subgroups and OS and ORR are in the table. 205 (60%) pts experienced a grade 3 or higher AE, the most common was hypertension (22% both arms; others

Conclusions

ICI combination rechallenge did not improve clinical outcomes, suggesting the avoidance of sequential ICI in advanced RCC outside of clinical trials. These results support tivozanib monotherapy at 1.34 mg daily as 2nd-line therapy for pts following progression on previous ICI combination therapy.

Clinical trial identification

NCT04987203.

Editorial acknowledgement

Editorial assistance was provided by Michael Malia, PhD, of AVEO Oncology. The authors provided input and critical review at all stages and approved the final version for submission.

Legal entity responsible for the study

AVEO Pharmaceuticals, Inc.

Funding

AVEO Pharmaceuticals, Inc.

Disclosure

T.K. Choueiri: Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS, Pfizer, Merck, Exelixis, AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: Lilly, EMD Serono, Infinity; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC drug: Ipsen; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: ResearchToPractice; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Other, Grant review to Orien Network ($400): ORIEN; 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