154P - Casdozokitug (casdozo, CHS-388), a first-in-class IL-27 antagonistic antibody, as monotherapy in treatment-refractory non-small cell lung cancer (NSCLC)

Background

Casdozo is the first in class and only clinical-stage IL-27 targeting antibody, which inhibits IL-27 signaling and T and NK cell immune inhibition leading to increased IFN-γ and NK cell gene activation in patients (pts) with cancer. A phase 1 dose-escalation and dose-expansion study of casdozo in advanced solid tumors demonstrated favorable safety and reversal of IL-27-mediated immune suppression. We present updated antitumor activity, safety, and biomarker data of casdozo monotherapy in pts with NSCLC.

Methods

A phase 1 dose-escalation and dose-expansion study explored casdozo monotherapy 10 mg/kg IV q4 wks in treatment-refractory NSCLC.

Results

As of August 27, 2024, 45 pts with NSCLC received casdozo (5 dose-escalation; 40 dose-expansion); median time on treatment was 8 wks; median follow-up time on study was 9 wks. Most had adenocarcinoma (73%) or squamous (25%) histology. The majority received casdozo as ≥3rd line (67%). Treatment-related adverse events (TRAEs) occurred in 18 (40%) of pts and were primarily grade 1/2 (fatigue was the most common, n=4 [9%]). Of the 43 response-evaluable pts, 2 partial responses were seen in anti-PD-(L)1-experienced pts with squamous histology, resulting in a 22% ORR in squamous NSCLC (2/9 pts). Immunohistochemistry of a responder’s archival squamous tumor showed an immune excluded phenotype by CD8 staining and presence of IL-27-expressing tumor associated macrophages (TAMs). Cytokine profiling of pt serum samples revealed a casdozo-induced increase in IFN-γ. Bulk RNAseq analysis of paired PBMC samples showed casdozo inhibited IL-27 signaling and activated NK and T cell signatures.

Conclusions

Casdozo, the only clinical-stage IL-27 antagonistic antibody, is well-tolerated as monotherapy and demonstrated antitumor activity in heavily pretreated, anti-PD-(L)1-experienced pts with squamous NSCLC. Biomarker data confirmed casdozo-mediated pharmacodynamic activity and immune activation. These findings support further evaluation of casdozo in pts with PD-1 experienced squamous NSCLC; a phase 1b study of casdozo with the anti-PD-1 inhibitor toripalimab is ongoing.

Clinical trial identification

NCT04374877.

Editorial acknowledgement

Olivia Adams The Phillips Group Oncology Communications, Inc.

Legal entity responsible for the study

Coherus BioSciences.

Funding

Coherus BioSciences.

Disclosure

A. Naing: Financial Interests, Personal, Speaker, Consultant, Advisor: CTI, Deka Biosciences, Janssen Biotech, Mural Oncology, NGM Bio, PsiOxus Therapeutics, Immune-Onc Therapeutics, STCube Pharmaceuticals, OncoSec KEYNOTE-695, Genome & Company, CytomX Therapeutics, Nouscom, Merck Sharp & Dohme, Servier, Lynx Health, AbbVie; Financial Interests, Personal, Speaker’s Bureau: 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), CME Outfitters; Financial Interests, Personal, Other: ARMO BioSciences, NeoImmuneTech, NGM Biopharmaceuticals, NCI, EMD Serono, MedImmune, Healios Onc Nutrition, Atterocor/Millendo, Amplimmune, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol Myers Squibb, Pfizer, CytomX, 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, GV20 Therapeutics. C. Mantia: Financial Interests, Institutional, Research Funding: Bristol Myers Squibb; Financial Interests, Personal, Speaker, Consultant, Advisor: Nextech, Cogent Biosciences; Financial Interests, Personal, Advisory Board: Synthekine. N. Pennell: Financial Interests, Personal, Speaker, Consultant, Advisor: Sanofi Genzyme, Bayer, Summit Therapeutics, Nuvation Bio, Genentech, BMS, Takeda, Johnson and Johnson, Eli Lilly; Financial Interests, Personal, Advisory Board: Iovance, Daiichi Sankyo. H.R. Kim: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Genentech/Roche; Financial Interests, Personal, Stocks or ownership: BridgeBio Therapeutics. L. Villaruz: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Johnson and Johnson, EMD Serono, Sanofi, Gilead, Daiichi Sankyo, Takeda, Jazz Pharmaceuticals. A.B. El-Khoueiry: Financial Interests, Personal, Advisory Board: Exelixis, AstraZeneca, Genentech, Agenus, Tallac, ABL Bio, Senti Biosciences, Qurient; Financial Interests, Institutional, Funding: Fulgent, Astex, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Merck, Genentech; Financial Interests, Personal, Coordinating PI: Genentech; Financial Interests, Institutional, Coordinating PI, trial; funding: Auransa; Non-Financial Interests, Personal, Principal Investigator: Agenus, Affimed, Bayer. D.E. Gerber: Financial Interests, Institutional, Research Grant: AstraZeneca, BerGenBio, Karyopharm, Novocure; Financial Interests, Personal, Royalties: Oxford University Press; Financial Interests, Personal, Speaker, Consultant, Advisor: Catalyst Pharmaceuticals; Financial Interests, Personal, Other, US Patent 11,747,345; U.S. patent applications 17/045,482, 63/386,387, 63/382,972, 63/382,257; US Patent; Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, Daiichi Sankyo, Elevation Oncology, Janssen Scientific Affairs, Jazz Pharmaceuticals, Regeneron Pharmaceuticals, Sanofi; Financial Interests, Personal, Leadership Role: OncoSeer Diagnostics, Inc. A. Qin: Financial Interests, Institutional, Research Grant: Genentech, AstraZeneca, Merck, Johnson and Johnson; Financial Interests, Personal, Speaker, Consultant, Advisor: Genentech, Pfizer, Johnson and Johnson, Regeneron, Summit Therapeutics, Strata Oncology; Financial Interests, Personal, Speaker’s Bureau: OncLive, MSHO, Medscape, Binaytara Foundation, Dava Oncology. M. Altan: Financial Interests, Personal, Advisory Board: GSK, Bristol Myers Squibb, Shattuck Lab, AstraZeneca, Insightec; Financial Interests, Personal, Invited Speaker: Nektar Therapeutics; Financial Interests, Personal, Other, Participation of independent data safety committee: Henlius; Financial Interests, Institutional, Other, Participation of Safety review committee for Nanobiotix-MDA Alliance: Nanobiotics; Financial Interests, Institutional, Local PI: Genentech, Nektar Therapeutics, Merck, GSK, Jounce Therapeutics, Bristol Myers Squibb, Shattuck Lab, Gilead, Verismo Therapeutics, Lyell. H. Tang, K. Iizuka, V. Kapoor, D. Chin: Financial Interests, Personal, Full or part-time Employment: Coherus BioSciences. T. Marron: Financial Interests, Personal, Advisory Board: Regeneron, AstraZeneca, Genentech, G1 Therapeutics, Arcus, Glenmark, Merck, NGMBio, Glenmark, AbbVie, Fate; Financial Interests, Institutional, Coordinating PI: Regeneron, Genentech, Boehringer Ingelheim, Merck. All other authors have declared no conflicts of interest.