TAK-981 + Pembrolizumab for Solid Cancers

Recruiting at 81 trial locations

Overseen By Anthony Olszanski

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Takeda

Must not be taking: CYP3A4/5 inhibitors, Pgp inhibitors

Disqualifiers: Uncontrolled brain metastasis, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

109 Participants Needed

Trial Summary

What is the purpose of this trial?

TAK-981 is being tested in combination with pembrolizumab to treat participants who have select advanced or metastatic solid tumors. The study aims are to evaluate the safety, tolerability, and preliminary efficacy of TAK-981 in combination with pembrolizumab. Participants will be on this combination treatment for 21-day cycles. They will continue with this treatment for up to 24 months or until participants meet any discontinuation criteria.

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

This trial is for adults with certain advanced or metastatic solid tumors that have relapsed or not responded to standard treatments. Eligible cancers include non-squamous and squamous NSCLC, cervical cancer, colorectal cancer (MSS-CRC), and cutaneous melanoma. Participants must have measurable disease, be in good physical condition (ECOG 0-1), have a heart function above a set threshold (LVEF ≥40%), recovered from previous therapy side effects, and adequate organ function.

Inclusion Criteria

Has at least 1 radiologically measurable lesion based on RECIST, Version 1.1

My cancer is advanced and cannot be removed by surgery.

I have recovered from side effects of my previous treatment, or they are stable.

Exclusion Criteria

I am taking or need to take strong medication that affects liver enzymes.

I had major surgery less than 14 days ago and haven't fully recovered.

I am currently being treated for an infection.

Treatment Details

Interventions

• Pembrolizumab
• TAK-981

Trial Overview The study tests TAK-981 combined with pembrolizumab on patients with specific solid tumors. The treatment involves cycles of 21 days each and can last up to two years unless there are reasons to stop earlier. Researchers want to see how safe this combo is, how well patients tolerate it, and if it effectively fights the cancer.

Participant Groups

Group I: Dose Expansion Phase: Cohort F: CPI Refractory Squamous or Nonsquamous NSCLC Experimental Treatment 2 Interventions

TAK-981 as IV infusion in participants with checkpoint inhibitors (CPI) refractory squamous or nonsquamous NSCLC on Days 1, 4, 8 and 11 or Days 1 and 8 or Days 1, 8 and 15 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

Group II: Dose Expansion Phase: Cohort E: Squamous NSCLC Experimental Treatment 2 Interventions

TAK-981 as IV infusion in participants with squamous non-small cell lung cancer (NSCLC) on Days 1, 4, 8 and 11 or Days 1 and 8 or Days 1, 8 and 15 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

Group III: Dose Expansion Phase: Cohort D: Cutaneous Melanoma Experimental Treatment 2 Interventions

TAK-981 as IV infusion in participants with cutaneous melanoma on Days 1, 4, 8 and 11 or Days 1 and 8 or Days 1, 8 and 15 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

Group IV: Dose Expansion Phase: Cohort C: MSS-CRC Experimental Treatment 2 Interventions

TAK-981 as IV infusion in participants with microsatellite stable colorectal cancer (MSS-CRC) on Days 1, 4, 8 and 11 or Days 1 and 8 or Days 1, 8 and 15 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

Group V: Dose Expansion Phase: Cohort B: Cervical Cancer Experimental Treatment 2 Interventions

TAK-981 as IV infusion in participants with cervical cancer on Days 1, 4, 8 and 11 or Days 1 and 8 or Days 1, 8 and 15 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

Group VI: Dose Expansion Phase: Cohort A: Non-squamous NSCLC Experimental Treatment 2 Interventions

TAK-981 as IV infusion in participants with non-squamous non-small cell lung cancer (NSCLC) on Days 1, 4, 8 and 11 or Days 1 and 8 or Days 1, 8 and 15 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

Group VII: Dose Escalation: TAK-981 + Pembrolizumab (Fixed Dose) Experimental Treatment 2 Interventions

Escalating doses of TAK-981 with starting dose of 40 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 or Days 1, 8 and 15 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until RP2D is determined (for a maximum of 24 months).

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+