TAK-500 + Pembrolizumab for Advanced Solid Cancers

Recruiting at 13 trial locations

Overseen By Anthony Olszanski

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Takeda

Must not be taking: Sting agonists, TLR agonists

Disqualifiers: Heart failure, Hepatitis, Lung 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: 63

61 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called TAK-500, alone or with pembrolizumab, in adults with advanced or spreading solid tumors. The goal is to see if TAK-500 is safe and effective in shrinking these tumors.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot have had certain treatments like other STING agonists/antagonists, Toll-like receptor agonists, or CCR2 agonists/antagonists within the past 6 months. Also, you must not have received any investigational products or anticancer therapy within 14 days or 5 half-lives before starting the study drug. It's best to discuss your current medications with the study doctor.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have received certain treatments like other investigational products or anticancer therapies within 14 days before starting the study drugs. It's best to discuss your current medications with the study doctor to get specific guidance.

What data supports the idea that TAK-500 + Pembrolizumab for Advanced Solid Cancers is an effective drug?

The available research shows that pembrolizumab, a part of the TAK-500 + Pembrolizumab combination, has been effective in treating certain types of cancer. For example, in patients with advanced non-small cell lung cancer, pembrolizumab improved survival rates compared to traditional chemotherapy. In one study, patients who received pembrolizumab lived longer and had a longer period before their cancer got worse compared to those who received chemotherapy. Additionally, pembrolizumab has shown benefits in treating advanced melanoma, where it improved survival and response rates compared to other treatments. These results suggest that pembrolizumab, when combined with TAK-500, could be an effective option for treating advanced solid cancers. ^{1 2 3 4 5}

What data supports the effectiveness of the drug pembrolizumab in treating advanced solid cancers?

Pembrolizumab has been shown to improve survival rates and slow disease progression in patients with advanced non-small cell lung cancer and melanoma, as demonstrated in several clinical trials. These studies indicate that pembrolizumab can be an effective treatment option for certain types of advanced cancers. ^{1 2 3 4 5}

What safety data is available for TAK-500 and Pembrolizumab in treating advanced solid cancers?

Pembrolizumab, also known as KEYTRUDA or MK-3475, has been evaluated in various clinical trials for different cancers. Safety data from these trials indicate that common adverse reactions include fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions such as pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders have also been reported. Pembrolizumab has shown clinical activity in solid tumors and is approved for certain cancers, but it can cause serious side effects like pneumonitis in 1%-5% of patients. There is no specific safety data provided for TAK-500 in the provided research. ^{2 5 6 7 8}

What safety information is available for pembrolizumab (Keytruda) in treating advanced solid cancers?

Pembrolizumab (Keytruda) has been used in various studies for different cancers, showing some common side effects like fatigue, cough, nausea, rash, and diarrhea. Serious immune-related side effects, such as lung inflammation (pneumonitis), liver inflammation (hepatitis), and thyroid problems, have also been reported, but these are less common. ^{2 5 6 7 8}

Is the drug Pembrolizumab (also known as Keytruda or MK-3475) a promising treatment for advanced solid cancers?

Yes, Pembrolizumab is a promising drug for advanced solid cancers. It has been approved for treating various cancers, including endometrial carcinoma, non-small-cell lung cancer, melanoma, and esophageal cancer. It works by helping the immune system fight cancer cells, and studies have shown it can improve survival rates and response to treatment. ^{2 4 5 9 10}

How is the drug TAK-500 + Pembrolizumab unique for treating advanced solid cancers?

This treatment combines TAK-500 with Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells, and is unique because it targets the PD-1/PD-L1 pathway, which is a novel approach in treating various solid tumors. Pembrolizumab has shown effectiveness in other cancers like non-small cell lung cancer and esophageal cancer, suggesting potential benefits in advanced solid cancers when combined with TAK-500. ^{2 4 5 9 10}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

Adults with certain advanced or metastatic solid tumors, including various cancers like lung, liver, breast, and stomach cancer. Participants must be in good physical condition (ECOG 0-1), have measurable disease per RECIST criteria, adequate organ function, and no severe side effects from previous treatments. They should not have heart issues or active hepatitis among other exclusions.

Inclusion Criteria

My liver function is relatively good (Child-Pugh A or B7).

My cancer has worsened or I can't tolerate standard treatments.

My blood, kidney, and liver tests are within normal ranges.

Exclusion Criteria

I have ongoing hepatitis B or C.

I haven't taken any experimental or cancer treatments in the last 14 days or 5 half-lives, whichever is shorter.

I have received a stem cell or organ transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive TAK-500 as a single agent or in combination with pembrolizumab to determine the recommended dose for expansion

Up to 1 year

Every 21 or 42 days

Dose Expansion

Participants receive TAK-500 at the recommended dose, either alone or with pembrolizumab, to evaluate safety and antitumor activity

Up to 1 year

Every 42 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 50 months

Treatment Details

Interventions

• Pembrolizumab
• TAK-500

Trial Overview The trial is testing TAK-500 alone or combined with pembrolizumab to evaluate safety and anti-tumor effects in adults with specific advanced cancers. Treatment can last up to a year but will stop if the disease progresses or at the doctor's discretion.

Participant Groups

Group I: Dose Expansion: 3L RCC: TAK-500 + Pembrolizumab (RDE 1) Experimental Treatment 2 Interventions

Participants with 3L renal clear cell carcinoma (RCC) will receive TAK-500, infusion, intravenously, in a 42-day treatment cycle (Q2W or Q3W) with pembrolizumab 200 mg infusion, intravenously, in a 42-day treatment cycle (Q3W) for up to 1 year. The recommended dose (RDE 1) and schedule of TAK-500 for expansion will be based on the results of the TAK-500 in combination with pembrolizumab Dose Escalation arm.

Group II: Dose Expansion: 3L NSCLC: TAK-500 (RDE 2) SA Experimental Treatment 1 Intervention

Participants with 3L NSCLC will receive TAK-500, infusion, intravenously, in a 42-day treatment cycle (Q2W or Q3W) for up to 1 year. The recommended dose (RDE 2) and schedule of TAK-500 for expansion will be based on the results of the TAK-500 as single agent in Dose Escalation arm.

Group III: Dose Expansion: 3L NSCLC: TAK-500 (RDE 1) SA Experimental Treatment 1 Intervention

Participants with third-line (3L) NSCLC will receive TAK-500, infusion, intravenously, in a 42-day treatment cycle (Q2W or Q3W) for up to 1 year. The recommended dose (RDE 1) and schedule of TAK-500 for expansion will be based on the results of the TAK-500 as single agent in Dose Escalation arm.

Group IV: Dose Expansion: 2L Pancreatic Adenocarcinoma: TAK-500 + Pembrolizumab (RDE 1) Experimental Treatment 2 Interventions

Participants with 2L Pancreatic Adenocarcinoma will receive TAK-500, infusion, intravenously, in a 42-day treatment cycle (Q2W or Q3W) with pembrolizumab 200 mg infusion, intravenously, in a 42-day treatment cycle (Q3W) for up to 1 year. The recommended dose (RDE 1) and schedule of TAK-500 for expansion will be based on the results of the TAK-500 in combination with pembrolizumab Dose Escalation arm.

Group V: Dose Expansion: 2L Pancreatic Adeno: TAK-500 (RDE 1) SA Experimental Treatment 1 Intervention

Participants with 2L Pancreatic Adenocarcinoma will receive TAK-500, infusion, intravenously, in a 42-day treatment cycle (Q2W or Q3W) for up to 1 year. The recommended dose (RDE 1) and schedule of TAK-500 for expansion will be based on the results of the TAK-500 as single agent in Dose Escalation arm.

Group VI: Dose Expansion: 2L NSCLC: TAK-500 + Pembrolizumab (RDE 2) Experimental Treatment 2 Interventions

Participants with 2L NSCLC will receive TAK-500, infusion, intravenously, in a 42-day treatment cycle (Q2W or Q3W) with pembrolizumab 200 mg infusion, intravenously, in a 42-day treatment cycle (Q3W) for up to 1 year. The recommended dose (RDE 2) and schedule of TAK-500 for expansion will be based on the results of the TAK-500 in combination with pembrolizumab Dose Escalation arm.

Group VII: Dose Expansion: 2L NSCLC: TAK-500 + Pembrolizumab (RDE 1) Experimental Treatment 2 Interventions

Participants with second-line (2L) non-small cell lung cancer (NSCLC) will receive TAK-500, infusion, intravenously, in a 42-day treatment cycle (Q2W or Q3W) with pembrolizumab 200 mg infusion, intravenously, in a 42-day treatment cycle (Q3W) for up to 1 year. The recommended dose (RDE 1) and schedule of TAK-500 for expansion will be based on the results of the TAK-500 in combination with pembrolizumab Dose Escalation arm.

Group VIII: Dose Escalation: TAK-500 Single Agent (SA) Experimental Treatment 1 Intervention

TAK-500 dose escalation starting at 8 microgram per kilogram (mcg/kg), infusion, intravenously, once on Day 1 of each 21-day treatment cycle (once every 3 weeks, Q3W) or once on Day 1, 15 and 29 of each 42-day treatment cycle (once every 2 weeks, Q2W), for up to 1 year.

Group IX: Dose Escalation: TAK-500 + Pembrolizumab Experimental Treatment 2 Interventions

TAK-500, infusion, intravenously, once on Day 1 of each 21-day treatment cycle (once every 3 weeks, Q3W) or once on Day 1, 15 and 29 of each 42-day treatment cycle (once every 2 weeks, Q2W), for up to 1 year, along with pembrolizumab 200 milligram (mg) infusion, intravenously, once on Day 1 of each 21-day treatment cycle or on Days 1 and 22 in a 42-day cycle (Q3W) for up to 1 year. The exact starting dose of TAK-500 will be determined from the results of the TAK-500 SA arm dose escalation.

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

Findings from Research

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

3. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]