Abstract 174P
Background
NGM707 is a humanized monoclonal antibody that binds the immune inhibitory receptors ILT2 and ILT4 and blocks interactions with their HLA ligands.
Methods
NGM707-IO-101 is a phase 1/2, dose escalation/expansion study evaluating NGM707 as a monotherapy and in combination with pembrolizumab. The monotherapy dose escalation enrolled eligible pts with advanced or metastatic solid tumors into escalating dose cohorts of NGM707 (6-1800 mg, Q3W iv). Primary objectives are to assess safety and tolerability of NGM707 and to identify phase 2 doses. Secondary/exploratory objectives include assessment of PK/biomarker correlation, immunogenicity and preliminary antitumor activity per RECIST v1.1.
Results
As of 21 Sep 2022, 33 pts have been enrolled in the monotherapy dose escalation at dose levels up to 1800 mg. Pts had received a median of 4 prior therapies (range 1-11) and all had metastatic disease. Treatment (Tx)-related adverse events (any grade/grade ≥3) occurred in 44%/9% of pts. One dose-limiting toxicity of pneumonitis (G5) in a pt with pulmonary metastasis was observed at 600 mg. A maximum tolerated dose was not reached and the maximum administered dose was 1800 mg. Linear PK was observed at doses ≥200 mg and analysis of peripheral immune cells demonstrated dose-dependent receptor occupancy (RO), with doses ≥200 mg maintaining ILT2 and ILT4 RO for the entire dosing interval. Preliminary evidence of myeloid reprogramming was observed in tumor biopsies, with reduction of the M2 macrophage marker CD163 observed post-treatment. Of 20 response-evaluable pts, best overall responses to date are stable disease in 6 pts and non-complete response/non-progressive disease in 1 pt. Five pts had reduced target lesion size with a maximum decrease in 1 pt of 28%. Seven pts remain on study with a maximum ongoing tx duration of 5 mo.
Conclusions
NGM707 monotherapy appears to be well tolerated at all dose levels. In this advanced, metastatic solid tumor cohort, early signals of efficacy were observed. Preliminary evidence of myeloid reprogramming was seen in tumor biopsies. Monotherapy tx is ongoing and enrollment of pembrolizumab combination cohorts has been initiated.
Clinical trial identification
NCT04913337.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Naing: Financial Interests, Personal, Funding: NCI, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor/Millendo, Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Eli Lilly, Kymab, PsiOxus, Arcus Biosciences, NeoImmuneTech, Immune-Onc Therapeutics, Surface Oncology, Monopteros Therapeutics, BioNTech SE, Seven & Eight Biopharma, SOTIO Biotech AG; Financial Interests, Personal, Advisory Board: Deka Biosciences, NGM Bio, PsiOxus Therapeutics, Immune-Onc Therapeutics, STCube Pharmaceuticals, OncoSec KEYNOTE-695, Pharming, Genome & Company, Horizon Therapeutics, CytomX Therapeutics, Kymab; Financial Interests, Personal, Other, Consulting: Nouscom, Merck Sharp & Dohme Corp, OncoNano, Servier, Lynx Health; Financial Interests, Personal, Invited Speaker: AKH Inc, The Lynx Group, Society for Immunotherapy of Cancer (SITC), Korean Society of Medical Oncology (KSMO), Scripps Cancer Care Symposium, ASCO Direct Oncology Highlights, European Society for Medical Oncology (ESMO), European Society for Immunodeficiencies (ESID), CME Outfitters. J.S. Wang: Financial Interests, Personal, Invited Speaker, Member of Speaker's Bureau for Tagrisso and Imfinzi: AstraZeneca; Financial Interests, Personal, Invited Speaker, Member of Speaker's Bureau for Lenvima: Eisai; Financial Interests, Personal, Advisory Board, Single Event - Advisory Board Participation: BioNTech, Janssen R&D, Stemline/Menarini; Financial Interests, Institutional, Invited Speaker: 7,8 Pharma, Black Diamond Therapeutics, Klus Pharma, Relay Therapeutics, H3 Biomedicine, Genentech/Roche, ORIC, Celgene/BMS, Olema Therapeutics, Novartis, Portola, MabSpace, Prelude Therapeutics, Treadwell Therapeutics, IGM Biosciences, Forty Seven, StingThera, PureTech Health, Aevi Genomics, Erasca, Artios Pharma, Nurix, Teneobio, BioTheryX, Boehringer Ingelheim, Biosplice, Zymeworks, Bayer Healthcare, ImmunoOnc, Cullinan, Immuno-Gen, Accutar, Blueprint, Hutchinson MediPharma, BioNTech, Macrogenics, TopAlliance, AstraZeneca, Revolution Medicines, Kymab, Clovis Pharma, Qilu Pugent Sound, Ribon Therapeutics, Xencor, LSK BioPartners, Syndax, Sanofi, Daiichi Sankyo, Phoenix Molecular Designs, Cyteir, Bicycle Therapeutics. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono , Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. All other authors have declared no conflicts of interest.