Abstract 161P
Background
IK-007 is a selective oral inhibitor of prostaglandin (PG) E2 receptor 4 (EP4). EP4 plays a key role in mediating PGE2-dependent immunosuppression and IK-007 may overcome mechanisms driving CPI resistance. MSS CRC is primary refractory to checkpoint inhibitors and high levels of PGE2 metabolite (PGEM) are associated with poor prognosis of CRC and may be predictive of response.
Methods
This is a phase 1b study of IK-007 in combination with pembro in patients with advanced or metastatic MSS CRC who have received at least 2 lines of prior therapy. Cohort 1 had a 7-day run-in with single agent IK-007 followed by IK-007 in combination with pembro (200 mg IV every 3 weeks), Cohort 2 received combination only. Endpoints included safety (mTPI design), antitumor activity (RECIST 1.1), pharmacokinetics, pharmacodynamics, and RP2D.
Results
Study enrolled 54 patients: 26 in Cohort 1 and 28 in Cohort 2 at 4 dose levels (300, 450, 600, and 900mg BID PO) with 12 patients prospectively enrolled with high urinary PGEM (enrichment). Median age was 70 years (28-82). Events of clinical interest included decreased renal function, liver toxicity, and upper GI ulcers. Treatment-related adverse events ≥ Grade 2 were reported in 26 patients (48%). Of these, increased AST was seen in 5 patients (9.3%). Serious adverse events (SAEs) were reported in 23 patients (43%) including intestinal obstruction, pneumothorax, and acute kidney injury. Two unrelated Grade 5 SAEs (cardiac arrest and aspiration pneumonia) were reported. A 5.3% ORR (2/39) was observed in the response population: 1 cCR (300mg BID) with DoR of 18+ months and 1 cPR (900mg Q12h) with DoR 4+ months (ongoing). Disease control rate was 28% (11/39) with the median duration of response of 8.3 months in the 5 patients with prolonged clinical benefit.
Conclusions
IK-007 in combination with pembro had an acceptable safety profile and showed limited antitumor activity in heavily pretreated MSS CRC patients. Correlation of response with PGEM status was inconclusive. Of note, 28% achieved disease control, many showing prolonged clinical benefit. Investigation in additional indication is warranted, including the ongoing IIT in inflammatory breast cancer.
Clinical trial identification
NCT03658772.
Legal entity responsible for the study
Ikena Oncology.
Funding
Ikena Oncology.
Disclosure
A.W. Tolcher: Financial Interests, Institutional, Advisory Board, Fees for consulting and advisory board memberships for Dr. Anthony Tolcher are paid to New Experimental Therapeutics, Llc d/b/a NEXT Oncology of which he is the CEO and Founder: Adagene, Inc., ARO Biotherapeutics, Bioinvent, Boehringer Ingelheim International GmbH, Deka Biosciences, Eleven Bio, Elucida, EMD Serono/ Merk KGaA, Immunome, NBE Therapeutics, Pelican, Pieris Pharma, Pyxis Oncology, Vincerx, Zymeworks Inc., MIRATI; Financial Interests, Institutional, Other, Fees for consulting and advisory board memberships for Dr. Anthony Tolcher are paid to New Experimental Therapeutics, Llc d/b/a NEXT Oncology of which he is the CEO and Founder: Asana BioSciences, Llc., Axlmmune, Bayer, Gilde Healthcare Partners, HBM Partners, Immunomet Therapeutics, Inc., Karma Oncology, Menarini Ricerche, Mersana, Nanobiotix, Partner Therapeutics, Pfizer Inc., Pierre Fabre, RYVU Therapeutics, Seattle Genetics, SOTIO Biotechnology Co., Spirea Limited Inc., Transcenta Therapeutics Inc., Trillium Therapeutics Inc., AbbVie, Inc, Agenus, Inc., Ascentage, Mekanistic Therapeutics; Financial Interests, Institutional, Other, Fees for consulting for Dr. Anthony Tolcher are paid to New Experimental Therapeutics, Llc d/b/a NEXT Oncology of which he is the President and Founder: Aclaris Therapeutics; Financial Interests, Institutional, Other, Fees for consulting for Dr. Anthony Tolcher are paid to New Experimental Therapeutics, Llc d/b/a NEXT Oncology of which he is President and Founder: Daiichi Sankyo, Inc.; Financial Interests, Institutional, Other, Note: Fees for consulting and advisory board memberships for Dr. Anthony Tolcher are paid to New Experimental Therapeutics, Llc d/b/a NEXT Oncology of which he is President and Founder: Immuneering, Impact Therapeutics US, Inc., Ocellaris Pharma, Inc. & Eli Lilly, SK Life Science, Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd; Financial Interests, Institutional, Advisory Board, NOTE: Fees for consulting and advisory board memberships for Dr. Anthony Tolcher are paid to New Experimental Therapeutics, Llc d/b/a NEXT Oncology of which he is President and Founder: ZielBio, Inc., Ikena Oncology, Hiber Cell, Inc.; Financial Interests, Institutional, Invited Speaker, Dr. Tolcher is the Director of Research, CEO and Founder of NEXT Oncology: NEXT Oncology; Financial Interests, Personal, Stocks/Shares: Pyxis Oncology; Financial Interests, Institutional, Invited Speaker, Fees for studies are paid for all study related costs, to New Experimental Therapeutics, Llc d/b/a NEXT Oncology of which Dr. Anthony Tolcher is CEO and Founder: Adagene Inc, Apros Therapeutics, Inc., AbbVie, Inc, Aminex Therapeutics, Inc., Amphivena Therapeutics, Inc., Arcellx, Inc., ARMO Biosciences, Arrys Therapeutics, Inc., Artios Pharma Limited, Asana BioSciences, Llc., Ascentage Pharma Group Inc., Astex Pharmaceuticals, Basilea Pharmaceutica International Ltd, BioInvent International AB, BioNTech RNA Pharmaceuticals GmbH, BioNTech RNA Pharmaceuticals GmbH, Birdie Biopharmaceuticals, HK Ltd., BJ Bioscience Inc., Codiak BioSciences, Inc., Boehringer Ingelheim Pharmaceutical, Inc., Boston Biomedical, Inc., Calgent Biotechnology Co., Ltd., CStone Pharmaceuticals (Suzhou) Co., Ltd., Cybrexa Therapeutics, Inc., Daiichi Sankyo Inc., Deciphera Pharmaceuticals, Llc, eFFECTOR Therapeutics, Inc, Eli Lilly and Company, EMD Serono, Gilead Sciences, Inc., GlaxoSmithKline Research & Development Limited, IDEAYA Biosciences, Haihe Biopharma Co., Ltd., Heat Biologics, IDEAYA Biosciences, ImmuneOncia Therapeutics, Inc., IMPACT Therapeutics, Inc., Inhibrx, Inc., Innate Pharma SA, Janssen Research & Development, K-Group Beta, Inc., KeChow Pharma, Inc., Kiromic Biopharma, Inc, Mabspace Biosciences (Suzhou) Co., Limited, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Mersana Therapeutics, Inc., Mirati Therapeutics, Inc., NatureWise Biotech & Medicals Corporation, Navire Pharma Inc., NBE-Therapeutics AG, NextCure, Inc, Nitto BioPharma, Inc., Odonate Therapeutics, Inc., Pelican Therapeutics, Inc., Petra Pharma, Pfizer, Inc., Pieris Pharmaceuticals, Inc., PMV Pharmaceuticals, Inc., Qilu Puget Sound Biotherapeutics Corporation, Samumed, Llc, Seattle Genetics, Inc., Spring Bank Pharmaceuticals, Inc., Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd., Symphogen A/S, Syndax Pharmaceuticals Inc., Synthorx, Inc., Takeda, Tizona Therapeutics, Zymeworks Inc.; Financial Interests, Institutional, Invited Speaker: ADC Therapeutics SA, Agenus Inc.; Financial Interests, Institutional, Invited Speaker, Fees for studies are paid for all study related costs, to New Experimental Therapeutics, Llc d/b/a NEXT Oncology of which Dr. Anthony Tolcher is CEO and Founder: ORIC Pharmaceuticals; Non-Financial Interests, Personal, Principal Investigator: AbbVie, Inc; Non-Financial Interests, Personal, Principal Investigator, Fees for studies are paid for all study related costs, to New Experimental Therapeutics, Llc d/b/a NEXT Oncology of which Dr. Anthony Tolcher is CEO and Founder: ABL Bio Inc., Adagene Inc, ADC Therapeutics SA, Agenus Inc., Aminex Therapeutics, Inc., Amphivena Therapeutics, Inc., Apros Therapeutics, Inc., Arcellx, Inc., ARMO Biosciences, Arrys Therapeutics, Inc., Artios Pharma Limited, Asana BioSciences, Llc., Ascentage Pharma Group Inc., Astex Pharmaceuticals, Basilea Pharmaceutica International Ltd, BioInvent International AB, Boehringer Ingelheim Pharmaceutical, Inc., BioNTech RNA Pharmaceuticals GmbH, Birdie Biopharmaceuticals, HK Ltd., BJ Bioscience Inc., Boston Biomedical, Inc., Calgent Biotechnology Co., Ltd., Codiak BioSciences, Inc., CStone Pharmaceuticals (Suzhou) Co., Ltd., Cybrexa Therapeutics, Inc., Daiichi Sankyo Inc., Deciphera Pharmaceuticals, Llc, eFFECTOR Therapeutics, Inc, Eli Lilly and Company, EMD Serono, Gilead Sciences, Inc., Ideaya Biosciences, GlaxoSmithKline Research & Development Limited, Haihe Biopharma Co., Ltd., Heat Biologics, ImmuneOncia Therapeutics, Inc., IMPACT Therapeutics, Inc., Inhibrx, Inc., Innate Pharma SA, Janssen Research & Development, K-Group Beta, Inc., KeChow Pharma, Inc. D.R. Spigel: Financial Interests, Institutional, Other, Consulting: Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Curio Science, EMD Serono, Evidera, Exelixis, Genentech/Roche, GlaxoSmithKline, Intellisphere, Ipsen Biopharmaceuticals, Janssen, Jazz Pharmaceuticals, Lilly, Mirati Therapeutics, Molecular Templates, Monte Rosa Therapeutics, Novartis, Pfizer, Puma Biotechnology, Regeneron, Sanofi-Aventis; Financial Interests, Institutional, Research Grant, Serve as PI: Amgen, Aeglea Biotherapeutics, Agios, Arrys Therapeutics, Astellas, AstraZeneca, Bayer, BeiGene, Bind Therapeutics, Blueprint Medicine, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celldex Therapeutics, Clovis, Daiichi Sankyo, Eisai, Lilly, EMD Serono, Genentech/Roche, G1 Therapeutics, Gilead Sciences, GlaxoSmithKline, GRAIL, Hutchinson MediPharma, ImClone Systems, Ipsen, Janssen, Loxo, MacroGenics, MedImmune, Merck, Nektar, Neon Therapeutics, Novartis, Novocure, PTC Therapeutics, Rgenix, SeaGen, Taiho Oncology, Tarveda, Tizona Therapeutics, Transgene, UT Southwestern, Verastem, Arcus Biosciences, Oncologie, Molecular Template, Cyteir Therapeutics, BioNTech, Apollomics, Pure Tech Health, Elevation Oncology, Repare Therapeutics, Kronos Bio, Razor Genomics, Denovo Biopharma, Erasca, Zai Laboratory, Faeth Therapeutics, Ascendis Pharma, Lyell Immunopharma, Synthekine, Shenzhen Chipscreen Biosciences. T. Lingaraj: Financial Interests, Institutional, Full or part-time Employment: Ikena. E. Talcove-Berko: Financial Interests, Institutional, Full or part-time Employment: Ikena. N. Ortiz-Otero: Financial Interests, Institutional, Full or part-time Employment: Ikena. W. Bartolini: Financial Interests, Personal, Full or part-time Employment: Ikena. K. Kacena: Financial Interests, Institutional, Full or part-time Employment: Ikena. S.L. Santillana: Financial Interests, Personal, Other, Individual expert consulting work in drug development supporting Biotechnology and Drug Development companies since 2019 under SLSS Consulting Llc work: SLSS Consulting Llc; Financial Interests, Institutional, Full or part-time Employment, Chief Medical Officer since July 2020: Ikena Oncology Inc; Financial Interests, Personal, Officer, Founder and President of SLSS Consulting Llc since 2019: SLSS Consulting Llc; Financial Interests, Institutional, Stocks/Shares, Stock options granted personally as Ikena employee: IkenaOncology Inc; Financial Interests, Personal, Ownership Interest, Owner and founder of individual consulting practice in SLSS Consulting Llc: SLSS Consulting Llc; Non-Financial Interests, Personal, Other, Mentor for Biotech Start Ups companies under MC organization program: Massachussets Challenge organization(MC); Other, Personal, Other, Nonprofit support /work as mentor of Biotechnology Start Up companies under MC program: Massachussets Challenge (MC). All other authors have declared no conflicts of interest.