A Study of TAK-500 With or Without Pembrolizumab in Adults With Select Locally Advanced or Metastatic Solid Tumors

An Open-label, Dose Escalation and Expansion, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of TAK-500, a Novel Stimulator of Interferon Genes Agonist, as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Select Locally Advanced or Metastatic Solid Tumors

This study is about TAK-500, given either alone or with pembrolizumab, in adults with select locally advanced or metastatic solid tumors.

The aims of the study are:

• to assess the safety profile of TAK-500 when given alone and when given with pembrolizumab.
• to assess the anti-tumor effects of TAK-500, when given alone and when given with pembrolizumab, in adults with locally advanced or metastatic solid tumors.

Participants may receive TAK-500 for up to 1 year. Participants may continue with their treatment if they have continuing benefit and if this is approved by their study doctor. Participants who are receiving TAK-500 either alone or with pembrolizumab will continue with their treatment until their disease progresses or until they or their study doctor decide they should stop this treatment.

Study Overview

• Status: Recruiting
• Conditions: Kidney Cancer; Breast Cancer; Nasopharyngeal Cancer; Gastric Cancer; Pancreatic Cancer; Esophageal Cancer; Mesothelioma; Hepatocellular Cancer; Squamous Cell Cancer of Head and Neck (SCCHN); Non-small Cell Lung Cancer (NSCLC), Non-squamous
• Intervention / Treatment: Drug: Pembrolizumab; Drug: TAK-500

Detailed Description

The drug being tested in this study is called TAK-500. The study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of TAK-500 when used as a single agent (SA) and in combination with pembrolizumab in participants with locally advanced or metastatic solid tumors.

The study will be conducted in 2 phases: Dose Escalation and Dose Expansion Phase. The study will enroll approximately 313 participants (approximately 82 in the Dose Escalation Phase and approximately 231 in Dose Expansion Phase). The dose escalation phase will determine the recommended dose of TAK-500 along with the combination agents for the dose expansion phase. All the participants will be assigned to one of the 9 arms:

• Dose Escalation: TAK-500 Single Agent (SA)
• Dose Escalation: TAK-500 + Pembrolizumab
• Dose Expansion: 2L NSCLC: TAK-500 recommended dose 1 for expansion (RDE 1) + Pembrolizumab
• Dose Expansion: 2L NSCLC: TAK-500 recommended dose 2 for expansion (RDE 2) + Pembrolizumab
• Dose Expansion: 3L NSCLC: TAK-500 (RDE 1) SA
• Dose Expansion: 3L NSCLC: TAK-500 (RDE 2) SA
• Dose Expansion: 2L Pancreatic Adenocarcinoma: TAK-500 (RDE 1) + Pembrolizumab
• Dose Expansion: 2L Pancreatic Adeno: TAK-500 (RDE 1) SA
• Dose Expansion: 3L RCC: TAK-500 (RDE 1) + Pembrolizumab

This multi-center trial will be conducted globally. Participants with demonstrated clinical benefit may continue treatment beyond 1 year if approved by the sponsor.

• Study Type: Interventional
• Enrollment (Estimated): 313
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Takeda Contact; Phone Number: +1-877-825-3327; Email: medinfoUS@takeda.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • Univeristy of Alabama at Birmingham
      • Contact: Site Contact; Phone Number: 919-525-0054; Email: aakashdesai@uabmc.edu
      • Principal Investigator: Aakash Desai
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Comprehensive Cancer Center
      • Contact: Site Contact; Phone Number: 626-256-9200; Email: vchung@coh.org
      • Principal Investigator: Vincent Chung
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California San Diego
      • Contact: Site Contact; Phone Number: 858-822-5354; Email: spatel@ucsd.edu
      • Principal Investigator: Sandep Patel
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado - Anschutz Medical Campus - PPDS
      • Principal Investigator: Jennifer Diamond
      • Contact: Site Contact; Phone Number: 303-724-5499; Email: jennifer.diamond@ucdenver.edu
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Sarah Cannon Research Institute
      • Contact: Site Contact; Phone Number: 720-754-4653; Email: jason.henry2@sarahcannon.com
      • Principal Investigator: Jason Henry
  • Florida
    • Miami, Florida, United States, 33136
      • Not yet recruiting
      • Sylvester Comprehensive Cancer Center
      • Contact: Site Contact; Phone Number: 305-396-8889; Email: estelarodriguez@miami.edu
      • Principal Investigator: Estela Rodriguez
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Northwestern
      • Contact: Site Contact; Phone Number: 312-695-6180; Email: jd-patel@northwestern.edu
      • Principal Investigator: Jyoti Patel
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Site Contact; Phone Number: 617-632-3000; Email: harshabad_singh@dfci.harvard.edu
      • Principal Investigator: Harshabad Singh
  • New York
    • New York, New York, United States, 10016-4744
      • Not yet recruiting
      • New York University
      • Contact: Site Contact; Phone Number: 212-731-5445; Email: minas.economides@nyulangone.org
      • Principal Investigator: Minas Economides
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
      • Contact: Site Contact; Phone Number: 215-214-1676; Email: anthony.olszanski@fccc.edu
      • Principal Investigator: Anthony Olszanski
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Not yet recruiting
      • Sarah Cannon Cancer Institute
      • Principal Investigator: Meredith Pelster
      • Contact: Site Contact; Phone Number: 615-329-7274; Email: meredith.pelster@sarahcannon.com
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Start South Texas Accelerated Research Therapeutics
      • Contact: Site Contact; Phone Number: 210-593-5265; Email: drew.rasco@startsa.com
      • Principal Investigator: Drew Rasco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. 2. 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 standard therapy:

1. 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.

2. For dose expansion in 2L nonsquamous NSCLC (TAK-500 plus pembrolizumab):

   • Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic nonsquamous NSCLC.
   • Participants may not have a known targetable driver mutation, rearrangement or amplification (eg, EGFR, ALK, MET, ROS1, BRAF, KRASG12C, etc.).

   • Must have had disease progression while on or following 1 prior line of therapy:

     1. Disease progression while on or following at least 6 weeks of 1 prior anti-PD-(L)1 therapy in the recurrent locally advanced or metastatic setting.

   OR Disease progression/recurrence within 6 months of the completion of anti-PD-(L)1 therapy if administered in the adjuvant/neoadjuvant setting.

   Prior anti-PD-(L)1 therapy may have been given with or without an anti-CTLA4 antibody and/or chemotherapy (eg, carboplatin and pemetrexed).

   • Participants are eligible regardless of PD-L1 status.

3. For dose expansion in 3L nonsquamous NSCLC (TAK-500 SA):

   • Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic nonsquamous NSCLC.
   • Participants may not have a known targetable driver mutation, rearrangement or amplification (eg, EGFR, ALK, MET, ROS1, BRAF, KRASG12C, etc.).

   • Must have had disease progression while on or following 2 prior lines of therapy:

     1. Disease progression while on or following at least 6 weeks of 1 prior anti-PD-(L)1 therapy in the recurrent locally advanced or metastatic setting OR Disease progression/recurrence within 6 months of the completion of 1 prior anti-PD-(L)1 therapy if administered in the adjuvant/neoadjuvant setting.

        Prior anti-PD-(L)1 therapy may have been given with or without an anti-CTLA4 antibody and/or chemotherapy (eg, carboplatin and pemetrexed).

     2. Participants must have had disease progression while on or after 1 or 2 lines of chemotherapy in the recurrent locally advanced or metastatic setting. If the anti-PD-(L)1 therapy is given in combination with chemotherapy, participant must have progressed on an additional line of chemotherapy.
   • Participants are eligible regardless of PD-L1 status.

4. For dose expansion in 2L pancreatic adenocarcinoma (TAK-500 SA and TAK-500 plus pembrolizumab):

   • Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic pancreatic adenocarcinoma.

   • Must have had disease progression while on or following 1 prior line of therapy:

   1. One prior line of fluorouracil- or gemcitabine-based chemotherapy (eg, FOLFIRINOX, FOLFOX, FOLFIRI, gemcitabine/nab-paclitaxel) in the metastatic/recurrent locally advanced setting.

   Prior chemotherapy in the neoadjuvant/adjuvant setting does not qualify unless the participant had progression of disease within 6 months of completion of neoadjuvant/adjuvant chemotherapy.

   • Must not have had prior exposure to anti-PD-(L)1 therapy.

   • Participants with MSI-H/dMMR disease are not eligible.

   • Participants are eligible regardless of PD-L1 status.

5. For dose expansion in 3L RCC (TAK-500 plus pembrolizumab):

   • Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic RCC.

   • Must have had disease progression while on or following 2 prior lines of therapy:

     1. Disease progression while on or following at least 6 weeks of 1 prior anti-PD-(L)1 therapy in the recurrent locally advanced or metastatic setting.

        OR Disease progression/recurrence within 6 months of the completion of anti-PD-(L)1 therapy if administered in the adjuvant/neoadjuvant setting.

        Prior anti-PD-(L)1 therapy may have been given with or without an anti-CTLA4 antibody and/or an anti-VEGFR TKI.

     2. Participants must have had prior therapy with 1 or 2 lines of VEGFR TKIs in the metastatic/recurrent locally advanced setting. If anti-PD-(L)1 therapy was given in combination with a VEGFR TKI, the participant must have had progressive disease on an additional line of therapy (eg, VEGFR TKI or VEGFR TKI-containing combination).

   • Participants are eligible regardless of PD-L1 status. 3. Must have at least 1 RECIST version 1.1 measurable lesion. Lesions in previously irradiated areas (or other local therapy) should not be selected as measurable/target lesions unless there has been demonstrated radiographic progression in that lesion. RECIST v1.1 target lesions must include at least 1 lesion that was not previously irradiated.

     4. Adequate bone marrow, renal, and hepatic functions, as determined by the following laboratory parameters:

   • Absolute neutrophil count (ANC) greater than or equal to (>=) 1000/microliter (mcL), platelet count >=75,000/mcL, and hemoglobin >= 8.0 grams per deciliter (g/dL) without growth factor support for ANC or transfusion support for platelets within 14 days before the first study treatment dose.
   • Total bilirubin <=1.5 times the institutional upper limit of normal (ULN). For participants with Gilbert's disease or HCC, <=3 milligrams per deciliter (mg/dL).
   • Serum alanine aminotransferase and aspartate aminotransferase <=3.0*ULN or <=5.0*ULN with liver metastases or HCC.
   • Albumin >=3.0 g/dL.

   • Calculated creatinine clearance using the Cockcroft-Gault formula >=30 mL/minute.

     5 . Left ventricular ejection fraction (LVEF) >50%, as measured by echocardiogram or multiple gated acquisition scan (MUGA) within 4 weeks before receiving the first dose of study drug.

     6. For participants with HCC only: Child-Pugh score less than or equal to 7 (Child-Pugh A or B7).

     7. Clinically significant toxic effects of previous therapy have recovered to Grade 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 5.0) or baseline, except for alopecia, Grade 2 peripheral neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement therapy.

     8. Participants previously treated with fully human/humanized antineoplastic monoclonal antibodies must not have received treatment with such antibodies for at least 4 weeks or the time period equal to the dosing interval, whichever is shorter. No washout period is required for prior treatment with pembrolizumab or other anti-programmed cell death protein 1 (PD-1) antibodies, although the first study dose of these drugs must not occur at an interval less than standard of care (that is, 3 weeks for 200 mg of IV pembrolizumab).

Exclusion Criteria:

1. 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.
2. QT interval with Fridericia correction method >450 milliseconds (men) or >475 milliseconds (women) on a 12- lead ECG during the screening period.
3. Grade >=2 hypotension (that is, hypotension for which nonurgent intervention is required) at screening or during C1D1 predose assessment.
4. Oxygen saturation <92% on room air at screening or during C1D1 predose assessment.
5. Treatment with other STING agonists/antagonists, Toll-like receptor agonists or CCR2 agonist/antagonist within the past 6 months.
6. Active diagnosis of pneumonitis, interstitial lung disease, severe chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, other restrictive lung diseases, acute pulmonary embolism, or Grade >=2 pleural effusion not controlled by tap or requiring indwelling catheters.
7. Grade >=2 fever of malignant origin.
8. Chronic, active hepatitis (example, participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus [HCV] RNA).
9. History of hepatic encephalopathy.
10. Prior or current clinically significant ascites, as measured by physical examination, that requires active paracentesis for control.
11. Treatment with any investigational products or other anticancer therapy (including chemotherapy, targeted agents, and immunotherapy), within 14 days or 5 half-lives, whichever is shorter, before C1D1 of study drug(s).
12. Radiation therapy within 14 days (42 days for radiation to the lungs) and/or systemic treatment with radionuclides within 42 days before C1D1 of study drug(s). Participants with clinically relevant ongoing pulmonary complications from prior radiation therapy are not eligible.

13. Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or within 14 days of C1D1 of study drug(s), with the following exceptions:

    • Topical, intranasal, inhaled, ocular, intra-articular, and/or other nonsystemic corticosteroids.
    • Physiological doses of replacement steroid therapy (example, for adrenal insufficiency), not to exceed the equivalent of 10 mg prednisone daily.
14. Recipients of allogeneic or autologous stem cell transplantation or organ transplantation.

Additional criteria specific for participants in TAK-500 and pembrolizumab combination arm only:

1. Contraindication to the administration of a pembrolizumab or prior intolerance to pembrolizumab or other anti-PD-1 or anti-programmed cell death protein ligand 1 antibody.
2. History of intolerance to any component of the study treatment agents or known serious or severe hypersensitivity reaction to any of the study drugs or their excipients. (Pembrolizumab is formulated with L-histidine, polysorbate 80, and sucrose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: TAK-500 Single Agent (SA); 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.	Drug: TAK-500; TAK-500 intravenous infusion.
Experimental: Dose Escalation: TAK-500 + Pembrolizumab; 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.	Drug: Pembrolizumab; Pembrolizumab intravenous infusion.; Drug: TAK-500; TAK-500 intravenous infusion.
Experimental: Dose Expansion: 2L NSCLC: TAK-500 + Pembrolizumab (RDE 1); 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.	Drug: Pembrolizumab; Pembrolizumab intravenous infusion.; Drug: TAK-500; TAK-500 intravenous infusion.
Experimental: Dose Expansion: 2L NSCLC: TAK-500 + Pembrolizumab (RDE 2); 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.	Drug: Pembrolizumab; Pembrolizumab intravenous infusion.; Drug: TAK-500; TAK-500 intravenous infusion.
Experimental: Dose Expansion: 3L NSCLC: TAK-500 (RDE 1) SA; 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.	Drug: TAK-500; TAK-500 intravenous infusion.
Experimental: Dose Expansion: 3L NSCLC: TAK-500 (RDE 2) SA; 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.	Drug: TAK-500; TAK-500 intravenous infusion.
Experimental: Dose Expansion: 2L Pancreatic Adenocarcinoma: TAK-500 + Pembrolizumab (RDE 1); 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.	Drug: Pembrolizumab; Pembrolizumab intravenous infusion.; Drug: TAK-500; TAK-500 intravenous infusion.
Experimental: Dose Expansion: 2L Pancreatic Adeno: TAK-500 (RDE 1) SA; 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.	Drug: TAK-500; TAK-500 intravenous infusion.
Experimental: Dose Expansion: 3L RCC: TAK-500 + Pembrolizumab (RDE 1); 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.	Drug: Pembrolizumab; Pembrolizumab intravenous infusion.; Drug: TAK-500; TAK-500 intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: Number of Participants With Grade 3 or Higher TEAEs	TEAE Grades will be evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.	Up to approximately 50 months
Dose Escalation: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs)		Up to approximately 50 months
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)	DLT will be defined as any of the TEAEs that occur during Cycle 1 and are considered by the investigator to be at least possibly related to TAK-500 as a SA or in combination with pembrolizumab. Toxicity will be evaluated according to NCI CTCAE version 5.0.	Up to approximately 50 months
Dose Escalation: Number of Participants Reporting one or More Serious Adverse Event (SAEs)		Up to approximately 50 months
Dose Escalation: Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations		Up to approximately 50 months
Dose Expansion: Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve confirmed partial response (cPR) or confirmed complete response (cCR) (determined by the investigator) during the study in the response-evaluable population. ORR will be assessed as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Complete response (CR): defined as disappearance of all target and non- target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than <10 mm. Partial response (PR): defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. cPR or cCR is defined as a PR or CR that is confirmed with additional imaging 6 weeks after initial response.	Up to approximately 50 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation and Dose Expansion: Cmax: Maximum Serum Concentration for TAK-500		Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1: pre-infusion and at multiple time points (up to 21 days) post-infusion (Cycle length=21 days)
Dose Escalation and Dose Expansion: Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAK-500		Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1: pre-infusion and at multiple time points (up to 21 days) post-infusion (Cycle length=21 days)
Dose Escalation and Dose Expansion: AUCt: Area Under the Serum Concentration-time Curve From Time 0 to Time t for TAK-500		Cycle 1 Day 1, and Cycle 2 Day 1: pre-infusion and at multiple time points (up to 21 days) post-infusion (Cycle length=21 days)
Dose Escalation and Dose Expansion: AUCinf: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAK-500		Cycle 1 Day 1, and Cycle 2 Day 1: pre-infusion and at multiple time points (up to 21 days) post-infusion (Cycle length=21 days)
Dose Escalation and Dose Expansion: t1/2: Terminal Disposition Phase Half-life for TAK-500		Cycle 1 Day 1, and Cycle 2 Day 1: pre-infusion and at multiple time points (up to 21 days) post-infusion (Cycle length=21 days)
Dose Escalation and Dose Expansion: CL: Total Clearance After Intravenous Administration for TAK-500		Cycle 1 Day 1, and Cycle 2 Day 1: pre-infusion and at multiple time points (up to 21 days) post-infusion (Cycle length=21 days)
Dose Escalation and Dose Expansion: Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-500		Cycle 1 Day 1, and Cycle 2 Day 1: pre-infusion and at multiple time points (up to 21 days) post-infusion (Cycle length=21 days)
Dose Escalation and Dose Expansion: Changes in Intratumoral Tumor Cell Infiltration	Measurement of changes in tumor immune cell infiltration will be measured by immunohistochemistry or in-situ hybridization on fresh tumor biopsies taken pre and post treatment (up to 23 days after first administration of TAK-500) for each participant.	Up to 23 days after first administration of TAK-500
Dose Escalation and Dose Expansion: Number of Participants With Positive Anti-drug Antibody (ADA) and Acquired Immunogenicity		Up to approximately 50 months
Dose Escalation: Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve cPR or cCR (determined by the investigator) during the study in the response-evaluable population. ORR will be assessed as per RECIST Version 1.1. CR: defined as disappearance of all target and non- target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than <10 mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. cPR or cCR is defined as a PR or CR that is confirmed with additional imaging 6 weeks after initial response.	Up to approximately 50 months
Dose Escalation and Dose Expansion: Disease Control Rate (DCR)	DCR is defined as the percentage of participants who achieve cCR + cPR + stable disease (SD) or better (determined by the investigator) greater than (>) 6 weeks during the study in the response-evaluable population. DCR will be assessed as per RECIST Version 1.1. CR: disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions.	Up to approximately 50 months
Dose Escalation and Dose Expansion: Duration of Response (DOR)	DOR is defined as the time from the date of first documentation of a cPR or better to the date of first documentation of PD for responders (cPR or better). Responders without documentation of PD will be censored at the date of last response assessment that is SD or better. DOR will be assessed as per RECIST Version 1.1. PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions.	Up to approximately 50 months
Dose Escalation and Dose Expansion: Time to Response (TTR)	TTR is defined as the time from the date of first dose administration to the date of first documented cPR or better (determined by the investigator) in the safety population. TTR will be assessed as per RECIST Version 1.1. PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.	Up to approximately 50 months
Dose Expansion: Progression Free Survival (PFS)	PFS is defined as the time from date of study treatment to the first documented PD based on RECIST v.1.1, or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of diameters of target lesions.	Up to approximately 50 months
Dose Expansion: Overall Survival (OS)	OS is defined as the time from the date of first dose administration to the date of death.	Up to approximately 50 months
Dose Expansion: Number of Participants With Grade 3 or Higher TEAEs	TEAE Grades will be evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.	Up to approximately 50 months
Dose Expansion: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs)		Up to approximately 50 months
Dose Expansion: Number of Participants With Dose Limiting Toxicities (DLTs)	DLT will be defined as any of the TEAEs that occur during Cycle 1 and are considered by the investigator to be at least possibly related to TAK-500 as a SA or in combination with pembrolizumab. Toxicity will be evaluated according to NCI CTCAE version 5.0.	Up to approximately 50 months
Dose Expansion: Number of Participants Reporting one or More Serious Adverse Event (SAEs)		Up to approximately 50 months
Dose Expansion: Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations		Up to approximately 50 months

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Estimated): August 11, 2026
• Study Completion (Estimated): August 11, 2026

Study Registration Dates

• First Submitted: September 24, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 7, 2021

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Adenoma; Neoplasms, Mesothelial; Head and Neck Neoplasms; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Liver Neoplasms; Neoplasms, Squamous Cell; Mesothelioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: TAK-500-1001; 2023-505374-15 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No