Abstract 822P
Background
The combination of Ipi + Nivo is frequently used as first line therapy in pts with MM, however, high rate of grade 3/4 immune related adverse events (irAEs) and treatment discontinuation pose a challenge for both physicians and pts. Our prior retrospective translational studies suggested that targeting interlukin-6 (IL-6) -Th17 pathway could be an effective approach to alleviate irAEs without hindering antitumor immunity. This supported initiation of phase II open-label, single center study (NCT04940299) to assess the safety and efficacy of adding Toci (anti-IL-6 receptor) to Ipi + Nivo for treatment naïve, unresectable stage III/IV MM.
Methods
A total of 35 MM pts will be enrolled; age ≥18 years (yrs), histologically confirmed locally advanced or MM including pts with stable asymptomatic brain mets. As of April 29, 2022, 18 pts were enrolled including 8 pts (45%) with stage IV M1c. Pts receive subcutaneous Toci 162 mg/2 weeks (wks) for 6 doses plus intravenously Ipi 3 mg/kg + Nivo 1 mg/kg/3 wks for up to 4 doses, then will continue Nivo 480 mg/4 wks up to 2 yrs. The primary objective includes safety and tolerability of this triplet. The secondary objectives include assessing the overall response rate (ORR) by RECIST v1.1. Longitudinal immune analysis of blood, tumor samples, and inflamed tissues will be performed to explore biomarkers of toxicity and tumor response.
Results
To date, 17 pts received at least 1 cycle of therapy and were evaluable for toxicity; 12 pts were evaluable for ORR. Follow-up ranged from 3 to 24 wks. Overall, 6 pts (35%) had grade 3 irAEs including diarrhea (n=5, 29%), elevated lipase (n=2, 11%), and elevated transaminases (n=1, 6%). Efficacy analysis demonstrated an ORR of 58% (1 CR and 6 PR) and disease control date of 75%. ORR in pts with elevated LDH was 44% (4/9 pts). One pt discontinued therapy due to toxicity; there have been no treatment-related deaths.
Conclusions
Our preliminary data of the combination of Toci plus Ipi3/Nivo1 is safe and well tolerated. The limited efficacy data reveal no negative impact of Toci on tumor immunity. Ongoing biomarker analysis will be presented to help further interpret study results.
Clinical trial identification
NCT04940299.
Editorial acknowledgement
Legal entity responsible for the study
This work is supported by the University of Texas MD Anderson Cancer Center Prioritizing Research Innovation and Mentoring Excellence Award (A.D. and N.A.), the University of Texas MD Anderson Cancer Center Immunotherapy Platform, and the National Institute of Health K01 Award (N.A: K01AI163412).
Funding
This work is supported by the University of Texas MD Anderson Cancer Center Prioritizing Research Innovation and Mentoring Excellence Award (A.D. and N.A.), the University of Texas MD Anderson Cancer Center Immunotherapy Platform, and the National Institute of Health K01 Award (N.A: K01AI163412).
Disclosure
N. Abdel-Wahab: Financial Interests, Personal, Invited Speaker: ChemoCentryx. R. Amaria: Financial Interests, Personal, Advisory Board: Iovance Biotherapeutics, Novartis, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Merck, Bristol Myers Squibb, Novartis, Iovance. S. Patel: Financial Interests, Personal, Invited Speaker, Peer discussion group leader for melanoma (non-promotional speaker / leader): Merck; Financial Interests, Personal, Advisory Board, Scientific Advisory Board: TriSalus; Financial Interests, Personal, Advisory Board: Cardinal Health; Financial Interests, Personal, Other, Independent Data Monitoring Committee: Immunocore; Financial Interests, Institutional, Invited Speaker: Provectus, Lvgen, Bristol Myers Squibb, InxMed, Foghorn Therapeutics, Ideaya. H.A. Tawbi: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Novartis, Genentech, Eisai, Karyopharm, Iovance, Pfizer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Merck, Novartis, Genentech; Financial Interests, Institutional, Funding: GSK, Eisai. P. Sharma: Financial Interests, Personal, Other, Consulting or Stock Ownership or Advisory Board: Achelois, Adaptive Biotechnologies, Affini-T, Phenomic AI, PBM Capital, Oncolytics, Marker, Lytix, Lava Therapeutics, Polaris Pharma, JSL Health, Infinity Pharma, ImaginAb, Hummingbird, Glympse, Earli, Dragonfly, Codiak, BioNTech, BioAtla, Apricity, Sporos, Time Bioventures, Venn Biosciences. A. Diab: Financial Interests, Personal, Advisory Board: Nektar Therpaeutics, Apexigen, Idera Pharmaceuticals. All other authors have declared no conflicts of interest.