Abstract 132TiP
Background
Despite recent improvements in treatment options for second-line, microsatellite-stable (MSS) mCRC, outcomes remain suboptimal. Here we describe the daNIS-3 study (a phase II, open-label, randomized, multicenter, platform study [NCT04952753]), which assesses the safety/efficacy of NIS793 (an anti–TGF-β monoclonal antibody), with a focus on exploratory biomarker assessments.
Trial design
For each investigational arm in the daNIS-3 study, an initial safety run-in (SRI) to confirm the NIS793 dose + SoC will be followed by expansion to randomization vs SoC. Eligible pts are adults with MSS mCRC not amenable to potentially curative surgery that has progressed within 6 months of a prior line of systemic therapy. SRI data will be analyzed after ≥6 pts in each regimen have received NIS793 (intravenous [IV] 2100 mg every 2 weeks or every 4 weeks) + bevacizumab (5 mg/kg) + FOLFIRI or NIS793 + bevacizumab + modified FOLFOX6 on Days 1 and 15 of each 28-day cycle. Analysis will be completed once all pts have received ≥1 cycle/met the minimum exposure criterion. Upon dose confirmation, further SRI of NIS793 + SoC + tislelizumab (tisle; 300 mg Q4W) will be performed, before pts (n=∼226) are randomized to resume the same investigational drug(s) + SoC (n=∼150) or SoC (n=∼76) alone. Biomarker assessments of baseline/archival tumor biopsies, to correlate with clinical responses will include PD-L1, CD8+ T cells and tumor mutational burden. On-treatment biopsies (Cycle 3/ end of treatment) will investigate changes in the tumor microenvironment and NIS793 resistance mechanisms. Analyses of serial blood samples will include circulating tumor DNA for disease monitoring and to correlate gene-oncogenic alterations with clinical efficacy; cytokine levels relating to clinical/immune responses; nucleic acids, to assess the effect(s) of TGF-β blockade; and immunophenotyping of peripheral blood mononuclear cells. daNIS-3 (NCT04952753) is an ongoing study, with pts from 87 sites planned, across 20 countries. The study start date was November 15, 2021.
Clinical trial identification
NCT04952753.
Editorial acknowledgement
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
S. Kasper: Financial Interests, Personal, Full or part-time Employment, An immediate family member: University Hospital Essen; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, MSD Oncology, AstraZeneca, Merck Serono, Amgen, Roche, Servier, Lilly, Sanofi/Aventis, Novartis, Pierre Fabre; Financial Interests, Personal, Advisory Role, Honoraria: Roche; Financial Interests, Personal, Advisory Role: Merck Serono, Amgen, MSD Oncology, Sanofi, Bristol Myers Squibb, Lilly, Servier, AstraZeneca, Janssen-Cilag, Novartis, Pierre Fabre; Financial Interests, Personal, Research Grant: Merck Serono, Bristol Myers Squibb, Celgene, Lilly, Servier, Roche/Genentech; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck Serono, Lilly, Amgen, Sanofi, Roche, Pierre Fabre, BMS; Financial Interests, Personal, Other: Sanofi, Amgen, Merck Serono, Bristol Myers Squibb, Roche, Lilly. N.H. Segal: Financial Interests, Personal, Advisory Role: Roche/Genentech, GlaxoSmithKline, ABL Bio, Boehringer Ingelheim, Novartis, Revitope, AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Pfizer, Roche/Genentech, Merck, Immunocore; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Regeneron, PureTech. F. Rivera: Financial Interests, Personal, Other, Honoraria: Roche, MSD, BMS, Servier, Novartis, Sanofi, AstraZeneca, Merck-Serono, Amgen, Lilly, Astellas; Financial Interests, Personal, Advisory Role: Roche, MSD, BMS, Servier, Novartis, Sanofi, AstraZeneca, Merck-Serono, Amgen, Lilly, Astellas; Financial Interests, Institutional, Research Grant: Roche, MSD, BMS, Servier, Novartis, Sanofi, AstraZeneca, Merck-Serono, Amgen, Lilly, Astellas; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Roche, MSD, BMS, Servier, Novartis, Sanofi, AstraZeneca, Merck-Serono, Amgen, Lilly, Astellas. C. Tournigand: Financial Interests, Personal, Other, Honoraria: Roche, Sanofi, Bayer, Bristol Myers Squibb, MSD; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Bayer, MSD. Y. Cheng: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Novartis. P. Deshpande: Financial Interests, Personal, Full or part-time Employment: Novartis. N. Amirouchene Angelozzi: Financial Interests, Personal, Full or part-time Employment: Novartis. A.P. Bento Pereira da Silva: Financial Interests, Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Roche, Novartis, Galapagos. A. St-Pierre: Financial Interests, Institutional, Full or part-time Employment: Novartis. S. Kopetz: Financial Interests, Personal, Advisory Role: Roche/Genentech, GlaxoSmithKline, ABL Bio, Boehringer Ingelheim, Novartis, Revitope, AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Pfizer, Roche/Genentech, Merck, Immunocore, AstraZeneca; Financial Interests, Institutional, Research Grant: Regeneron, PureTech.