TAK-981 + Pembrolizumab for Solid Cancers

No longer recruiting at 86 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: 42

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two treatments: TAK-981 (an experimental treatment) and pembrolizumab (also known as KEYTRUDA, an immunotherapy drug). The goal is to determine their safety and effectiveness for people with certain advanced or hard-to-treat cancers, such as non-small cell lung cancer, cervical cancer, melanoma, and colorectal cancer that have not responded to standard treatments. The trial involves 21-day treatment cycles, which can continue for up to 24 months if the treatment is tolerated and effective. Individuals with specific types of cancer that have not improved with previous treatments might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but you cannot take certain drugs that affect liver enzymes or are strong inhibitors of specific proteins. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of TAK-981 and pembrolizumab is generally safe for patients with certain solid tumors. In one study, patients with non-small cell lung cancer (NSCLC) and microsatellite stable colorectal cancer (MSS-CRC) experienced manageable side effects, which were not severe enough to halt treatment.

Pembrolizumab, one of the drugs in this combination, has FDA approval for treating various cancers, including NSCLC, indicating it is usually well-tolerated. TAK-981, when combined with pembrolizumab, showed promise in early studies, with no unexpected safety issues reported.

Overall, early findings suggest that combining TAK-981 with pembrolizumab is safe. Most participants in these studies tolerated the treatment well, which is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of TAK-981 and pembrolizumab for treating solid cancers because it offers a novel approach to tackling these conditions. Unlike traditional therapies that might focus solely on blocking cancer growth, TAK-981 works by enhancing the body's immune response to cancer cells. This is achieved by inhibiting SUMOylation, a process that some cancers exploit to avoid immune detection. When combined with pembrolizumab, a well-known immune checkpoint inhibitor, the treatment aims to bolster the immune system's ability to recognize and attack tumors more effectively. This dual-action approach is particularly promising for patients whose cancers have become resistant to other immune-based treatments.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that combining TAK-981 with pembrolizumab, which participants in this trial may receive, may help treat certain advanced solid tumors. This trial includes various treatment arms, such as those for non-small cell lung cancer (NSCLC) and microsatellite stable colorectal cancer (MSS-CRC), where this combination is being tested. Studies indicate that this combination is generally safe and may help shrink tumors. Pembrolizumab alone effectively treats metastatic cancers, and adding TAK-981 might enhance these effects. Early results suggest that this combination could help control the disease and offer lasting benefits. However, more research is needed to confirm its effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of TAK-981 with a fixed dose of pembrolizumab to determine the recommended phase 2 dose (RP2D)

Up to 24 months

Multiple visits per 21-day cycle

Dose Expansion

Participants receive TAK-981 and pembrolizumab in defined cohorts based on cancer type, continuing until disease progression or for a maximum of 24 months

Up to 24 months

Multiple visits per 21-day cycle

Follow-up

Participants are monitored for progression-free survival and other outcomes after the last dose of study drug

Up to 12 months

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04381650

NCT04381650 | A Study of TAK-981 Given With ... TAK-981 is being tested in combination with pembrolizumab to treat participants who have select advanced or metastatic solid tumors.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.2506

A phase 1b, multicenter, dose-escalation study of ... Subasumstat plus pembrolizumab showed a favorable safety profile and promising anti-tumor activity in pre-treated NSCLC and MSS-CRC pts.

3. dana-farber.org dana-farber.org/clinical-trials/22-233

A Phase 1b/2 Study of TAK-981 Plus Pembrolizumab to ... TAK-981 is being tested in combination with pembrolizumab to treat participants who have select advanced or metastatic solid tumors.

4. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2020-004325-23/HR

Clinical Trials Register To evaluate the efficacy of TAK-981 in combination with pembrolizumab in select solid tumors as measured by disease control rate (DCR), durable ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11651430/

Pembrolizumab alone or combined with chemotherapy versus ... Conclusions: Pembrolizumab alone or combined with chemotherapy indicates an effective and safe treatment for metastatic cancer. Pembrolizumab ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/125514s096lbl.pdf

Keytruda - accessdata.fda.gov HIGHLIGHTS OF PRESCRIBING INFORMATION. These highlights do not include all the information needed to use. KEYTRUDA safely and effectively. See full prescribing.

7. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) non–small cell lung cancer (NSCLC) in combination with ...