TAK-500 + Pembrolizumab for Advanced Solid Cancers
Recruiting in Palo Alto (17 mi)
+13 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Waitlist Available
Sponsor: Takeda
No Placebo Group
Breakthrough Therapy
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.
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.12345
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.25678
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.245910
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.
See 10 more
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.
See 18 more
Treatment Details
Interventions
- Pembrolizumab (Monoclonal Antibodies)
- TAK-500 (Other)
Trial OverviewThe 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
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.
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Sarah Cannon Research InstituteDenver, CO
Univeristy of Alabama at BirminghamBirmingham, AL
City of Hope Comprehensive Cancer CenterDuarte, CA
Sylvester Comprehensive Cancer CenterMiami, FL
More Trial Locations
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Who Is Running the Clinical Trial?
TakedaLead Sponsor
References
Pembrolizumab: A Review in Advanced Melanoma. [2022]Pembrolizumab (Keytruda(®)) is a humanized monoclonal antibody against programmed death receptor-1 (PD-1), a key immunoinhibitory checkpoint protein implicated in down-regulating anti-tumour immune responses. This intravenous drug is indicated for the treatment of advanced (unresectable or metastatic) melanoma, on the basis of its clinical benefit in this setting in the phase I KEYNOTE 001 trial (expansion cohorts) and the phase II and III trials, KEYNOTE 002 and 006. These studies were conducted in ipilimumab-naïve and/or ipilimumab-experienced patients and assessed varying pembrolizumab regimens administered every 2 or 3 weeks, all of which helped to determine the recommended dosage of 2 mg/kg every 3 weeks. In the trials with active comparator arms, pembrolizumab regimens significantly improved progression-free survival (PFS), overall survival (OS) and overall response rates (ORR) relative to ipilimumab in ipilimumab-naïve patients (KEYNOTE 006), and significantly improved PFS and ORR, but not OS (although OS data are immature), relative to chemotherapy in ipilimumab-refractory patients, who had also received BRAF/MEK inhibitor therapy if BRAF-mutation positive (KEYNOTE 002). Pembrolizumab has an acceptable tolerability profile, with immune-related adverse events that are generally manageable/reversible. Thus, pembrolizumab is a valuable treatment option for patients with advanced melanoma, including those who have progressed on ipilimumab and BRAF/MEK inhibitors.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.Approval was based on two randomized, open-label, active-controlled trials demonstrating statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTE-024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41-0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37-0.68; p < .001). In KEYNOTE-010, patients with disease progression on or after platinum-containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58-0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49-0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy.
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]In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
New Approved Use for Keytruda. [2022]Pembrolizumab (Keytruda) is now approved as a single agent to treat advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient in those whose disease has progressed following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation.
Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]Pembrolizumab (Keytruda) has been approved to treat metastatic or locally advanced esophageal or gastroesophageal junction cancer. It is used in combination with platinum- and fluoropyrimidine-based chemotherapy.