122P - Casdozokitug (casdozo, SRF388), a first-in-class IL-27 targeting antibody, as monotherapy (monotx) or in combination with pembrolizumab (pembro) in treatment-refractory non-small cell lung cancer (NSCLC)

Background

Casdozo neutralizes immunoregulatory IL-27 to stimulate antitumor immunity. In preclinical studies, casdozo + anti-PD-1 enhanced immune activation and inflammatory cytokine production. A Ph 1 dose escalation study of casdozo in advanced solid tumors demonstrated favorable safety and reversal of IL-27-mediated immune suppression as evidenced by increases in serum IFN-g and NK cell gene activation. We present antitumor activity and safety of casdozo as monotx and with pembro in NSCLC patients (pts).

Methods

A Ph 1 dose escalation study triggered Ph 2 expansion cohorts exploring casdozo 10 mg/kg IV q4 wks as monotx and q3 wks in combination with pembro in treatment-refractory NSCLC. Tumor response was assessed by RECIST1.1.

Results

As of July 12, 2023, 51 pts received casdozo as monotx (5 dose escalation; 40 expansion) or with pembro (n=6). Most had adenocarcinoma (73%) or squamous (25%) histology. The majority received casdozo as 3rd line or greater (67%). Treatment-related adverse events (TRAEs) occurred in 44% on monotx. TRAEs were primarily grade 1/2, with fatigue being most common (9%, n=4). Of the 41 response-evaluable monotx pts, 2 pts with primary resistance to aPD-(L)1 experienced confirmed, durable partial responses and remained on therapy ≥6 mo. Responders had squamous disease and no or low (10%) archival tumor PD-L1 expression. The monotx ORR in the 7 RECIST-evaluable pts with squamous disease was 29%. IHC of a responder’s archival squamous tumors showed an immune excluded phenotype by CD8 staining and a high density of peritumoral IL-27+ macrophages. In the PD-1 relapsed/refractory combination cohort (n=6), no responses in the 4 response-evaluable pts, high-grade TRAEs or study drug discontinuations have been reported.

Conclusions

The only clinical stage anti-IL-27 targeting antibody, casdozo, is well tolerated with monotx antitumor activity in heavily pretreated, PD-(L)1 experienced NSCLC. Given the antitumor activity, safety, and tolerability of the pembro combination, as well as casdozo’s distinct mechanism, a Ph 2 study will investigate casdozo + toripalimab (aPD-1).

Clinical trial identification

NCT04374877.

Editorial acknowledgement

Editorial assistance was provided by Mark Phillips, PharmD, MBA, with The Phillips Group Oncology Communications, Inc.

Legal entity responsible for the study

Surface Oncology.

Funding

Surface Oncology.

Disclosure

T.U. Marron: Non-Financial Interests, Personal, Advisory Role: Regeneron, BI, AZ, DBV technologies, Celldex, Surface Oncology, NGM Biopharmaceuticals, Glenmark, AbbVie; Non-Financial Interests, Personal and Institutional, Proprietary Information: Surface Oncology; Financial Interests, Personal, Research Funding: Regeneron, BMS, Merck, BI. A. Naing: Non-Financial Interests, Personal, Full or part-time Employment: MDACC; Non-Financial Interests, Personal and Institutional, Advisory Role: CytomX Therapeutics, OncoSec, STCube Pharmaceuticals, Genome and Co, Deka Biosciences, NGM Biopharmaceuticals, PsiOxus Therapeutics, Nouscom, Merck Sharp & Dohme, OncoNano, Servier, Lynx Health, AbbVie, PsiOxus Therapeutics, Takeda, Pharming NV, Horizon T; Other, Personal, Financially compensated role: ARMO Biosciences, NeoImmuneTech, NGM Biopharmaceuticals; Other, Personal, Other: AKH Inc, Lynx Group, Society for Immunotherapy of Cancer, KSMO, Scripps Hospital, ASCO, ESMO, CME outfitters; Financial Interests, Personal, Research Funding: NCI, EMD Serono, MedImmune, Atterocor, Amplimmune, ARMO biosciences, Karyopharm, Incyte, Novartis, Regeneron, Merck, BMS, Pfizer, CytomX Therapeutics. C. Mantia: Financial Interests, Personal, Advisory Board, I participated in a one-time advisory board: Aadi Bioscience; Financial Interests, Institutional, Coordinating PI, Institutional funding for research: Bristol Myers Squibb. N. Pennell: Non-Financial Interests, Personal, Advisory Role: Lilly, Merck, Genentech, Pfizer, Mirati Therapeutics, Janssen Oncology, Sanofi, ResistanceBio, Takeda, Novartis, Vial, Bayer, Anheart Therapeutics, Summit Therapeutics, Lovance Biotherapeutics; Financial Interests, Institutional, Research Funding: AZ, Merck, Loxo, Spectrum Pharmaceuticals, BMS, Mirati Therapeutics, Sanofi, Anheart Therapeutics, Navire. H.R. Kim: Non-Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical, Roche/Genentech. A.B. El-Khoueiry: Non-Financial Interests, Personal, Advisory Role: BMS, Bayer, Eisai, Roche, Merck, Exelixis, Pieris Pharmaceuticals, Agenus, Gilead, AZ/MedImmune, ABL bio, QED Therapeutics, SERVIER, Tallac Therapeutics, Senti Biosciences, Qurient; Non-Financial Interests, Personal, Royalties: Bayer, BMS, Roche/Genentech, EMD Serono, Eisai, Merck, Agenus, Exelixis, Gilead, AZ/MedImmune, ABL bio, QED Therapeutics, Servier, Tallac Therapeutics, Senti Biosciences, Qurient; Non-Financial Interests, Personal, Research Funding: AZ, Astex, Fulgent. D.E. Gerber: Non-Financial Interests, Personal, Advisory Role: Catalyst Pharmaceuticals, Janssen Oncology, Sanofi, Regeneron, DSI, Elevation Oncology; Non-Financial Interests, Personal, Proprietary Information: UTSD; Other, Personal, Other: OncoSeer Diagnostics; Financial Interests, Personal, Stocks or ownership: Gilead, Walgreens; Financial Interests, Institutional, Research Funding: BerGenBio, Karyopharm, AZ, Novocure. A. Qin: Non-Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Institutional, Research Funding: Takeda, Clovis Oncology, Merck, Xencor, AZ, Roche. M. Altan: Non-Financial Interests, Personal, Advisory Role: BMS, GSK, AZ; Non-Financial Interests, Personal, Speaker’s Bureau: Nektar; Financial Interests, Institutional, Research Funding: Lilly, BMS, Novartis, GSK, Jounce, Adaptimmune, Merck, Genentech, Nektar, Shattuck Labs. L.J. Appleman: Non-Financial Interests, Personal, Advisory Role: AADi; Financial Interests, Institutional, Research Funding: Pfizer, Exelixis, BMS, Astellas Pharma, Novartis, Bayer, Merck, Genentech, AVEO, Peloton Therapeutics, Calithera Biosciences, Seagen, Inovio Pharmaceuticals, Eisai, Lilly, Amgen, Surface Oncology, BioNTech, Epizyme, Janssen Oncology, Ipsen, Arvinas. J. Hill: Non-Financial Interests, Personal, Full or part-time Employment: Surface Oncology; Non-Financial Interests, Personal, Proprietary Information: Surface Oncology; Financial Interests, Personal, Stocks or ownership: Surface Oncology; Financial Interests, Personal, Research Funding: Surface Oncology. V. Reichert: Non-Financial Interests, Personal, Full or part-time Employment: Coherus Biosciences, Surface Oncology, Deciphera; Financial Interests, Personal, Stocks or ownership: Coherus Biosciences, Surface Oncology, Deciphera; Non-Financial Interests, Personal, Advisory Role: Kineta, Checkpoint Therapeutics. R. Masia: Non-Financial Interests, Personal, Full or part-time Employment: Surface Oncology. L. Harshman: Financial Interests, Personal, Full or part-time Employment: Surface Oncology; Financial Interests, Personal, Stocks or ownership: Surface Oncology. A. Patnaik: Financial Interests, Institutional, Other, Institutional research funding: Compugen. D. Morgensztern: Non-Financial Interests, Personal, Advisory Role: AbbVie, G1 Therapeutics, Lilly Medical, Mirati Therapeutics, Arcus Biosciences; Financial Interests, Personal, Stocks or ownership: BMS, Abbott Labratories; Financial Interests, Institutional, Research Funding: Heat Biologics, Merck, Celgene, AZ, Baxter, Incyte, AbbVie, BMS, EpicentRx, Pfizer, Roche, Lilly, Altum Pharmaceuticals, Array Biopharma, Surface Oncology, Arcus Biosciences, BI, Y-mAbs Therapeutics. All other authors have declared no conflicts of interest.