1077TiP - TAK-500 as a single agent and in combination with pembrolizumab in patients (pts) with advanced solid tumors: Rationale and design of a phase I/II study

Background

TAK-500 is a novel immune-cell-directed antibody drug conjugate comprising the STING agonist TAK-676 conjugated to a human IgG1 anti-C-C chemokine receptor 2 (CCR2) antibody. In preclinical models, treatment with the TAK-500 murine surrogate resulted in activation of innate and adaptive immunity and antitumor activity, which was increased when combined with an anti-PD-1 antibody. Based on these data, a phase 1/2 open-label, dose-escalation and expansion study was designed to determine safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of TAK-500 as a single agent and in combination with pembrolizumab in CCR2-enriched solid tumors (NCT05070247). Phase 1 has been previously described (Diamond et al, ASCO, 2022 ), here we present the phase 2 design.

Trial design

Approximately 231 patients with treatment-refractory, advanced or metastatic non-squamous non-small cell lung cancer (NS NSCLC), pancreatic adenocarcinoma (PDAC), or renal clear cell carcinoma (RCC) will be enrolled. Eligible patients will receive TAK-500 intravenously as a single agent or with pembrolizumab 200 mg every 3 weeks. Randomized comparisons of two dose levels of TAK-500 (DL1 and DL2) as a single agent and in combination with pembrolizumab will be carried out as follows: patients with 2^nd-line NS NSCLC will be randomized 2:1 to receive TAK-500 at DL1 or DL2 with pembrolizumab while patients with 3^rd-line NS NSCLC will be randomized 1:1 to receive single-agent TAK-500 at DL1 or DL2. Patients with 2^nd-line PDAC will be randomized 1:1 to TAK-500 at a single dose level alone or with pembrolizumab. A single cohort of patients with 3^rd-line RCC will receive single-agent TAK-500 with pembrolizumab at DL1. A Simon’s 2-stage design with futility analyses based on response per RECIST v1.1 will be used for 2^nd-line NS NSCLC and 2nd-line PDAC. A single-stage statistical design will be utilized for 3^rd-line NS NSCLC and RCC. As of May 2023, 6 sites in the United States are recruiting; the global phase 2 is planned to start in 2024.

Clinical trial identification

NCT05070247.

Editorial acknowledgement

Medical writing, under the direction of the authors, was provided by Helen Wilkinson, PhD, of Ashfield MedComms, an Inizio company, funded by Takeda Pharmaceuticals, U.S.A., Inc., Lexington, MA, and complied with GPP guidelines (DeTora LM, et al. Ann Intern Med 2022 ;175:1298–1304).

Legal entity responsible for the study

Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.

Funding

Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.

Disclosure

H. Singh: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting: Dewpoint, Merck. J.R. Diamond: Financial Interests, Personal, Advisory Board, Payment for consulting services: Gilead; Financial Interests, Personal, Stocks/Shares: OnKure, Inc; Financial Interests, Institutional, Research Grant: Merck, Gilead, Cosmo, Takeda, Adlai Nortye, AZ, HutchMed, Seattle Genetics; Financial Interests, Personal, Advisory Role, Payment for consulting services: Consultant, OnKure, Inc.. J.T. Henry: Financial Interests, Personal, Other, Travel: Sarah Cannon Research Institute; Financial Interests, Institutional, Local PI: Abbiscko Therapeutics, ABl bio, Accutar biotech ADC therapeutics, Agenus, Aileron Therapeutics, Amgen Inc, Artios, AstraZeneca, Bicycle therapeutics, BioAlta, BioInvent pharma, Biosplice therapeutics, Black diamond therapeutics, Boehringer, Cyteir, Daiichi Sankyo, Eli Lilly, Epizyme, Erasca, Exelixis, FujiFilm, GSK, Hutchison MediPharma, ICON plc, IGM Biosciences, Immunitas, Immunogen, Ingelheim, Jazz Pharmaceuticals, Jacobio pharmaceuticals, Jounce pharma, Jubilant therapeutics, Loxo oncology, Merck& CO, Metabomed, Mirati, Molecular templates, Navire Pharma, Nikang pharmaceuticals, Oncorus, Poseida, Prelude therapeutics, PureTech, Pyxis, Pyramid, Rascal Therapeutics, Regeneron, Relay Therapeutics, Rgenix inc, Ribon therapeutics, Sapience, Sarah Cannon Development Innovations, Sarah Cannon Research Institute, Seagen, Simcha Therapeutics, Siranomics, Stingthera, Synthorx inc, Takeda pharmaceuticals, Tallac therapeutics, Tarveda, Teneothree, Tesaro, Turning point pharma, Xencor; Financial Interests, Personal, Stocks/Shares: HCA; Financial Interests, Personal, Full or part-time Employment: Sarah Cannon Research Institute. A.J. Olszanski: Financial Interests, Personal, Advisory Board: Merck, Pfizer, BMS. D. Rasco: Non-Financial Interests, Personal, Principal Investigator: Takeda; Financial Interests, Personal, Sponsor/Funding: Takeda. S.P. Patel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Certis, Eli Lilly, Jazz, Genentech, Illumina, Merck, Pfizer, Rakuten, Tempus; Financial Interests, Personal, Research Grant: Amgen, AstraZeneca/MedImmune, Bristol Myers Squibb, Eli Lilly, Fate Therapeutics, Gilead, Iovance, Merck, Pfizer, Roche/Genentech, SQZ Biotechnologies. R. Gregory: Financial Interests, Personal, Full or part-time Employment: Takeda; Financial Interests, Personal, Stocks/Shares: Takeda. V.A. Appleman: Financial Interests, Personal, Full or part-time Employment: Takeda Development Center Americas; Financial Interests, Personal, Stocks/Shares: Takeda Development Center Americas. J.P. Gibbs: Financial Interests, Personal, Full or part-time Employment: Takeda; Financial Interests, Personal, Stocks/Shares: Takeda. W. Zhang: Financial Interests, Personal, Full or part-time Employment: Takeda Pharmaceutical Company ; Financial Interests, Personal, Stocks/Shares: Takeda Pharmaceutical Company . C.I. Wang: Financial Interests, Personal, Full or part-time Employment: Takeda; Financial Interests, Personal, Stocks/Shares: Takeda. A.A. Parent: Financial Interests, Personal, Full or part-time Employment: Takeda Pharmaceuticals Company Limited; Financial Interests, Personal, Stocks/Shares: Takeda Pharmaceuticals Company Limited. V. Chung: Financial Interests, Personal, Speaker’s Bureau: Ipsen, AstraZeneca; Financial Interests, Institutional, Research Grant: Merck.