2372P - Efficacy of a tailored approach with nivolumab (N) and nivolumab+ipilimumab (N+I) as immuno-therapeutic boost in metastatic urothelial carcinoma (mUC): Final results of TITAN-TCC

Background

N is approved in 2L mUC after platinum-based chemotherapy. Studies suggest improved outcomes for dual checkpoint inhibition in particular with high doses of ipilimumab (N 1mg/kg + I 3mg/kg). We report final data of TITAN-TCC, NCT03219775, that used a tailored approach with N and N+I boosts for non-response.

Methods

Pts with mUC started N induction (240mg Q2W x4). Non-responders of cohorts 1 (dose escalation) and 2 (high dose ipilimumab) received N+I boosts as reported in the table. Responders to N induction continued with N maintenance (240mg Q2W), but could receive N+I per the respective schedules for later progression. Repeated boost phases were possible. Primary endpoint was objective response rate (ORR) to N ± N+I per RECIST1.1. Secondary endpoints included ORR to N induction, progression-free survival (PFS), and overall survival (OS).

Results

TITAN-TCC was conducted from 08/2017 to 02/2023. In cohort 1, 42 pts were 1L and 44 2/3L. Cohort 2 recruited 2/3L pts only with 83 being enrolled. For follow-up times see the table. ORR to N induction was 29%, 23%, and 20% for cohort 1 – 1L, cohort 1 – 2/3L, and cohort 2, respectively. In total, 105 pts received any boost doses, 14 had repeated boost phases. Best overall response to N ± N+I was 48% (95% CI 32-64), 27% (95% CI 15-43), and 33% (95% CI 23-44), respectively. 1-, 2-, and 3- year OS rates were 55%, 37%, and 31% for cohort 1 – 1L, 42%, 31%, and 18% for cohort 1 – 2/3L, and 40%, 34%, and 34% for cohort 2. For median OS and PFS see the table. Table: 2372P

Conclusions

Despite meaningful clinical activity of the TITAN-TCC approach in cohort 1 – 1L, starting treatment with N monotherapy appears inadequate given the aggressiveness of mUC. In 2/3L, N+I boosts with escalating dose of ipilimumab (cohort 1 – 2/3L) did not improve ORR vs. N monotherapy as reported in the literature. However, it did for boosts with high dose ipilimumab (cohort 2) with a considerable 3-year OS rate for 2/3L mUC.

Clinical trial identification

NCT03219775.

Editorial acknowledgement

Legal entity responsible for the study

AIO-Studien-gGmbH.

Funding

Bristol Myers Squibb.

Disclosure

M. Grimm: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Ipsen Pharma, Merck Serono, MSD, Pfizer, EUSA, Janssen, Oncinfo; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, EUSA Pharma, Ipsen Pharma, Merck Serono, MSD, Pfizer, Roche, Eisai, Takeda, Janssen Cilag, Gilead, Novartis; Financial Interests, Personal, Member of Board of Directors: Deutsche Gesellschaft für Urologie; Financial Interests, Personal and Institutional, Coordinating PI: Bristol Myes Squibb; Financial Interests, Institutional, Local PI: Intuitive Surgical; Financial Interests, Institutional, Coordinating PI: Bayer. M. Schostak: Financial Interests, Personal, Advisory Board, and honoraria for speaking: AstraZeneca, Bristol Myers Squibb, Janssen, Merck, Sharp & Dome, Merck, Bayer Vital; Financial Interests, Personal, Advisory Board: Novartis, Roche; Financial Interests, Institutional, Local PI: AstraZeneca, Bayer Vital, Bristol Myers Squibb, Janssen, Merck, Ferring. C.B. Grün: Financial Interests, Institutional, Advisory Board, Advisory board: Bayer Vital; Financial Interests, Personal, Advisory Board, Interview concerning therapy of metastatic colorectal cancer 12/2021: Dr. Rönsberg GmbH Health Marketing; Financial Interests, Personal, Other, registration fee for congress DGHO meeting (online) 10/2021: Sanofi Genzyme. F. Roghmann: Financial Interests, Personal, Advisory Board: Janssen, Roche, Merck, Pfizer, QED; Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca. G. Niegisch: Financial Interests, Personal, Advisory Board: Sanofi, Roche, Sanofi, BMS, Merck, Pfizer, Ipsen, Janssen, Ingress Health; Financial Interests, Personal, Writing Engagement: Pfizer, BMS; Financial Interests, Personal, Invited Speaker: Roche, Pfizer, BMS, Medac, AstraZeneca, Astellas; Financial Interests, Personal, Other, Congress registration, travel expenses: Roche, Pfizer, Merck; Non-Financial Interests, Project Lead: S3 guideline bladder cancer; Non-Financial Interests, Leadership Role: Interdissciplinary Bladder Cancer Working Group. G. Baretton: Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, MSD, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Astellas, Daiichi Sankyo; Other, Personal, Other, Travel Expanses: MSD. K. Leucht: Other, Institutional, Writing Engagement: BMS, Intuitive Surgicals; Other, Personal, Non financial benefits: Ipsen. S. Foller: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, AstraZeneca, MSD, Ipsen Pharma, Merck Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Merck Pfizer, Roche, Bristol Myers Squibb. F. Zengerling: Financial Interests, Personal, Advisory Board: Apogepha Pharma GmbH, AstraZeneca Germany GmbH, Bristol Myers Squibb GmbH, Roche Pharma GmbH; Financial Interests, Personal, Advisory Board, Consulting fees and honoraria for lectures: Astellas Pharma GmbH, Bayer Vital GmbH, Ipsen Pharma GmbH, Janssen-Cilag GmbH, Merck Healthcare Germany GmbH, Pfizer Pharma GmbH; Financial Interests, Personal, Invited Speaker: Sanofi-Aventis Deutschland GmbH. All other authors have declared no conflicts of interest.