dazostinag (TAK-676)

P1, N=34, Completed, Takeda | Active, not recruiting --> Completed | N=65 --> 34

P1, N=65, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting

P1, N=15, Completed, Presage Biosciences

P1/2, N=368, Recruiting, Takeda | Phase classification: P1 --> P1/2 | Trial completion date: Jul 2025 --> Oct 2025 | Trial primary completion date: Jul 2025 --> Oct 2025

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. A single-stage statistical design will be utilized for 3rd-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.

Conclusions Preliminary safety, PK/PD data, and anti-tumor activity support the declaration of the RDE of dazostinag 5 mg + pembro 200 mg. Expansion cohorts in colorectal and head and neck cancer are enrolling.

Single agent α-PD-1 treatment also resulted in a 12.5% CR rate, however, when combined, mTAK-500 and α-PD-1 treatment achieved enhanced anti-tumor response with a 37.5% CR rate. Conclusions Nonclinical antitumor activity and mechanistic insight have motivated design and clinical testing of TAK-500, a CCR2-targeted STING ISAC comprising the clinical stage STING agonist TAK-676 and a high-affinity antibody targeting human CCR2, as a single agent and in combination with pembrolizumab in adults with select locally advanced or metastatic solid tumors ( NCT05070247 ).

P1, N=288, Recruiting, Takeda | N=76 --> 288 | Trial completion date: Mar 2023 --> Jul 2025 | Trial primary completion date: Mar 2023 --> Jul 2025

P1 | "The primary objective is to determine the safety and tolerability of TAK-676 plus pembrolizumab following radiation therapy; secondary objectives are to establish the recommended phase 2 dose of TAK-676 plus pembrolizumab following radiation therapy, and to assess preliminary antitumor activity both locally (within the radiation field) and systemically (non-radiated lesions). As of February 2022, we have enrolled ̃10% of the planned pts."

These studies highlight TAK-676’s potential to promote anti-tumor immunity and the utility of the CIVO platform to reveal and characterize combination-specific responses. This application of CIVO is being further evaluated in an ongoing Phase 0 trial in patients with head and neck squamous cell carcinoma (NCT04541108).

P1, N=24, Recruiting, Presage Biosciences | N=36 --> 24

P1, N=36, Recruiting, Presage Biosciences | Not yet recruiting --> Recruiting | N=12 --> 36 | Initiation date: Feb 2021 --> Jun 2021

Adult pts with histologically confirmed advanced or metastatic solid tumors who have no standard therapeutic options or are intolerant to them, with an Eastern Cooperative Oncology Group (ECOG) performance status 0–1, and ≥1 Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1- evaluable lesion are eligible; pts with tumors that have relapsed, are refractory or naïve to anti-programmed death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) therapy are eligible for the combination arm . Planned enrollment is ̃76 pts; recruitment is ongoing.

P1, N=12, Not yet recruiting, Presage Biosciences | Trial completion date: Dec 2030 --> Dec 2031 | Initiation date: Nov 2020 --> Feb 2021 | Trial primary completion date: Dec 2030 --> Dec 2031

P1, N=12, Not yet recruiting, Presage Biosciences

P1; N=76; Recruiting; Sponsor: Millennium Pharmaceuticals, Inc.; Not yet recruiting --> Recruiting

P1, N=76, Not yet recruiting, Millennium Pharmaceuticals, Inc.