1450MO - Efficacy of a tailored approach with nivolumab and nivolumab/ipilimumab as immunotherapeutic boost in metastatic renal cell carcinoma: Final results of TITAN-RCC

Background

The combination of nivolumab 3 mg/kg + ipilimumab 1 mg/kg (nivo+ipi) is an approved 1^st line (1L) therapy for patients with metastatic renal cell carcinoma (mRCC) and intermediate / poor risk. TITAN-RCC investigated a response-based approach with nivo induction and nivo+ipi boost in non-responders. We report final study results for 1L and 2L (after TKI) patients.

Methods

From OCT 2016 to DEC 2018 207 patients with intermediate/poor risk mRCC started nivo induction (Q2W, 240 mg). Patients with early progressive disease (PD, week 8) or non-responders at week 16 (stable disease [SD]/PD) received 2-4 doses nivo+ipi. Responders to nivo induction (complete/partial response [CR/PR]) continued with nivo maintenance but could receive nivo+ipi for later PD. The primary endpoint was confirmed objective response rate (ORR) per RECIST in 1L and 2L. Secondary endpoints included efficacy of nivo induction, response to boost, progression free (PFS) and overall survival (OS), and safety.

Results

Of the 207 patients, 109 were 1L and 98 2L. Median age was 65 yr, 71 % of patients had intermediate and 25 % poor risk. Confirmed response to nivo induction was 28 % in 1L and 18 % in 2L. After 33.6 months from last patient first treatment and 15.9 months median follow-up, ORR for nivo ± nivo+ipi was 36 % in 1L (significant >25 %, p<0.05) and 32 % in 2L. Irrespective of time point, 44% (1L) and 53% (2L) of patients receiving boosts for PD upon nivo improved in best response. PFS was 6.3 months (95 % CI 3.7-10.1) in 1L and 3.7 months (95 % CI 1.8-4.5) in 2L. OS was 32.0 months (95 % CI 22.9-39.4) in 1L and 25.9 months (95 % CI 17.8-33.7) in 2L. No new safety signals emerged. Table: 1450MO

Response to nivo+ipi boost

Conclusions

Nivo+ipi boosts improve outcomes compared to nivo monotherapy. Responses were also observed after progression during nivo maintenance suggesting a potential role as rescue strategy. However, overall efficacy of our tailored approach appears to be inferior compared to upfront nivo+ipi treatment.

Clinical trial identification

EudraCT: 2016-002307-26, NCT02917772.

Editorial acknowledgement

Legal entity responsible for the study

AIO-Studien-gGmbH.

Funding

Bristol Myers Squibb.

Disclosure

M. Grimm: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Bristol Myers Squibb, Ipsen Pharma, Merck Serono, MSD, Pfizer, EUSA, Janssen, Oncinfo, Deutsche Gesellschaft für Urologie; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, EUSA Pharma, Ipsen Pharma, Merck Serono, MSD, Pfizer, Roche, Eisai, Takeda, Astellas, Ingress Health, Janssen Cilag; Financial Interests, Personal and Institutional, Invited Speaker: Bristol Myes Squibb; Financial Interests, Institutional, Invited Speaker: Intuitive Surgical. P. Barthelemy: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck, Pfizer, Ipsen, Bayer, Janssen Cilag, Astellas, Novartis, Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Seagen. M. Schmidinger: Financial Interests, Personal, Advisory Board, advisory boards or lectures: BMS, MSD, Merck, Ipsen; Financial Interests, Personal, Invited Speaker: EUSA, Janssen; Financial Interests, Personal, Advisory Board: Alkermes, Exelixis; Financial Interests, Personal, Advisory Board, Advisory board or lectures: Eisai; Financial Interests, Institutional, Research Grant, Research grant for retropsective study: Ipsen. J. Busch: Financial Interests, Personal, Invited Speaker: BMS, Merck, Ipsen, Pfizer, Janssen, Astellas; Financial Interests, Personal, Advisory Board: MSD, Merck, Ipsen, BARD, AstraZeneca. B. Perez Valderrama: Financial Interests, Personal, Advisory Board: Pfizer, Astellas Pharma, Bristol Myers Squibb, Ipsen, EUSA Pharma, Sanofi-Aventis, Merck, MSD, AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Roche, Bayer, EUSA Pharma, MSD, Merck, Pfizer, Janssen, Astellas Pharma. N. Charnley: Financial Interests, Institutional, Funding: BMS; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Funding: Ipsen, EUSA. G. Baretton: Financial Interests, Personal, Advisory Role: BMS, MSD, AstraZeneca, Roche, Novartis; Financial Interests, Institutional, Funding: BMS, MSD; Financial Interests, Personal, Other, Honoria: Pfizer, Roche, MSD, BMS, AstraZeneca. I. Duran Martinez: Financial Interests, Personal, Advisory Board, I have served as an advisor for this company in the last two years: Roche Genentech, MSD, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, I have participated in different compensated educational activities sponsored by Jansen over the last two years: Jansen; Financial Interests, Personal, Invited Speaker, I have participated in different compensated educational activities sponsored by Pfizer over the last two years: Pfizer; Financial Interests, Personal, Advisory Board, I have collaborated as an advisor in different occasions over the last two years: ipsen; Financial Interests, Personal, Invited Speaker, I have participated in different compensated educational activities sponsored by this company over the last two years: IPSEN, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, I have collaborated as an advisor for this company in the last two year: Merck; Financial Interests, Personal, Advisory Board, I have participated in different compensated advisory boards over the last two years: Astellas; Financial Interests, Personal, Advisory Board, I have collaborated as an advisor for this company over the last two years: Immunomedics, Inc.; Financial Interests, Personal, Invited Speaker, I have participated in educational activities sponsored by this company in the last two years: EUSA Pharma, MSD; Financial Interests, Personal, Invited Speaker, I have participated in educational activities sponsored by Novartis in the last 2 years: Novartis; Financial Interests, Personal, Invited Speaker, I have participated in compensated educational activities for this company in the last two years: Astellas; Financial Interests, Personal and Institutional, Research Grant, Roche has funded research in my institution to projects under my coordination: Roche Genentech; Financial Interests, Personal, Invited Speaker, I serve as a member of a SC for a trial sponsored by this company: Immunomedics, Inc.; Financial Interests, Personal and Institutional, Research Grant, AZ has funded research conducted in my institution related to a project where I am the PI: AstraZeneca; Non-Financial Interests, Leadership Role, I am the president of an independent cooperative group of GU Oncologist from the north of Spain: GO NORTE; Non-Financial Interests, Invited Speaker, I belong as a external advisor to the board of directors of the Spanish Association of cancer research since 2021: ASEICA. G.A. De Velasco Oria: Financial Interests, Personal, Advisory Board: Pfizer, astellas, BMS, MSD, Ipsen, Bayer, Eusa P., Merck; Financial Interests, Personal, Invited Speaker: Pfizer, astellas, BMS, MSD, Roche, Ipsen, Merck; Financial Interests, Institutional, Research Grant: Roche. F. Priou: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca. J.P. Maroto Rey: Non-Financial Interests, Advisory Role: Bayer, MSD, Astellas, Merck. L. Albiges: Financial Interests, Institutional, Other, Consulting: Astellas, AstraZeneca, BMS, Eisai, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer; Non-Financial Interests, Principal Investigator: Pfizer, BMS, Ipsen, AVEO, AstraZeneca, MSD; Non-Financial Interests, Other, Clinical trial steering committee: Roche, Exelixis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Other, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology (EAU); Non-Financial Interests, Other, Member of the Kidney Cancer Research Summit scientific committee 2021: Kidney Can; Other, Scientific Committee: BMS France. All other authors have declared no conflicts of interest.