What side effects are associated with this type of intervention?

Common treatments for kidney cancer, particularly immunotherapies and targeted therapies, have a range of side effects. Pembrolizumab and nivolumab, often used in combination with other agents, can cause fatigue, rash, diarrhea, and immune-related adverse events such as pneumonitis and colitis. Ipilimumab, when combined with nivolumab, can increase the risk of severe immune-related side effects. Sunitinib and pazopanib, both tyrosine kinase inhibitors, are associated with hypertension, hand-foot syndrome, diarrhea, and liver toxicity. These side effects are generally manageable but require close monitoring by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of kidney cancer, particularly focusing on immune checkpoint inhibitors and targeted therapies. Notable approvals include nivolumab (Opdivo) and pembrolizumab (Keytruda), both of which are anti-PD-1 therapies used either alone or in combination with other agents like ipilimumab (Yervoy) or axitinib (Inlyta). These drugs work by enhancing the body's immune response against cancer cells. Additionally, combinations such as pembrolizumab with axitinib and nivolumab with ipilimumab have shown significant efficacy in treating advanced renal cell carcinoma. These treatments are similar to the investigational drug TAK-500, which is being studied for its anti-tumor effects in combination with pembrolizumab.

What other types of research exist?

Promising novel alternatives to TAK-500 for kidney cancer patients include: 1) Cabozantinib, which has shown efficacy in advanced renal cell carcinoma, particularly after prior tyrosine kinase inhibitor therapy. 2) Pembrolizumab, an immune checkpoint inhibitor, which has been effective in combination with other agents like axitinib and lenvatinib. 3) Nivolumab, another immune checkpoint inhibitor, which has demonstrated safety and efficacy in various trials for advanced renal cell carcinoma. 4) Atezolizumab, often used in combination with bevacizumab, has shown positive results in metastatic renal cell carcinoma. These alternatives offer different mechanisms of action and have been validated in clinical settings, making them viable options for treatment in 2024.

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Monoclonal Antibodies

TAK-500 + Pembrolizumab for Advanced Solid Cancers

Phase 1 & 2

Recruiting

Research Sponsored by Takeda

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.

Individuals with the following pathologically confirmed (cytological diagnosis is adequate) select locally advanced or metastatic solid tumors, whose disease has progressed on or are intolerant to all standard therapy: gastroesophageal (esophageal, gastroesophageal junction, and gastric) adenocarcinoma, pancreatic adenocarcinoma, hepatocellular carcinoma (HCC), nonsquamous non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), mesothelioma, triple-negative breast cancer (TNBC), renal clear cell carcinoma (RCC) and nasopharyngeal carcinoma (NPC). Participants who are intolerant to all standard therapies are those who have developed clinical or laboratory abnormalities that prevent continued drug administration as evaluated by the principal investigator at the time of screening.

Must not have

History of any of the following <=6 months before first dose of study drug(s): congestive heart failure New York Heart Association Grade III or IV, unstable angina, myocardial infarction, persistent hypertension >=160/100 millimeters of mercury (mmHg) despite optimal medical therapy, ongoing cardiac arrhythmias of Grade >2 (including atrial flutter/fibrillation or intermittent ventricular tachycardia), other ongoing serious cardiac conditions (example, Grade 3 pericardial effusion or Grade 3 restrictive cardiomyopathy), or symptomatic cerebrovascular events. Chronic, stable atrial fibrillation on stable anticoagulation therapy, including low molecular-weight heparin, is allowed.

Grade >=2 hypotension (that is, hypotension for which nonurgent intervention is required) at screening or during C1D1 predose assessment.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 50 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as inflammation of organs, infusion-related reactions which may cause discomfort during treatment administration, fatigue, digestive disturbances like nausea or diarrhea, blood cell count changes that could increase infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can carry out all my daily activities without help.

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

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My kidneys are functioning well enough, based on a specific test.

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't had serious heart or stroke issues in the last 6 months.

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I have had low blood pressure that needed treatment.

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I do not have severe lung conditions or uncontrolled fluid in my lungs.

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I have a high fever caused by cancer.

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I have ongoing hepatitis B or C.

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I have had episodes of brain confusion due to liver problems.

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I have had or have serious fluid buildup in my abdomen needing drainage.

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

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I haven't had radiation therapy in the last 14 days (or 42 days for lung radiation) or radionuclide treatment in the last 42 days.

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I am on a low dose of steroids, not more than 10 mg of prednisone daily.

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I have received a stem cell or organ transplant.

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I cannot take pembrolizumab or similar drugs due to previous bad reactions or other reasons.

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I am allergic to components in the study drugs, including L-histidine, polysorbate 80, or sucrose.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 50 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 50 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 50 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)

Dose Escalation: Number of Participants With Grade 3 or Higher TEAEs

Dose Expansion: Overall Response Rate (ORR)

Secondary study objectives

Dose Escalation and Dose Expansion: Changes in Intratumoral Tumor Cell Infiltration

Dose Escalation and Dose Expansion: Disease Control Rate (DCR)

Dose Escalation and Dose Expansion: Duration of Response (DOR)

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

9Treatment groups

Experimental Treatment

Group I: Dose Expansion: 3L RCC: TAK-500 + Pembrolizumab (RDE 1)Experimental Treatment2 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) SAExperimental Treatment1 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) SAExperimental Treatment1 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 Treatment2 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) SAExperimental Treatment1 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 Treatment2 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 Treatment2 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 Treatment1 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 + PembrolizumabExperimental Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for kidney cancer, such as immune checkpoint inhibitors (e.g., pembrolizumab) and targeted therapies, work by enhancing the immune system's ability to recognize and attack cancer cells or by inhibiting specific pathways that tumors use to grow and spread. Immune checkpoint inhibitors block proteins that prevent immune cells from attacking cancer, thereby boosting the body's natural defenses. Targeted therapies, on the other hand, interfere with molecular signals that promote tumor growth and survival. Understanding these mechanisms is important for kidney cancer patients as it provides insight into how these treatments can effectively manage their disease and improve outcomes.

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