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

Sponsor
Takeda (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05070247
Collaborator
(none)
106
7
3
35.4
15.1
0.4

Study Details

Study Description

Brief Summary

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 effects of TAK-500, when given alone and when given with pembrolizumab, on 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.

Detailed Description

The drug being tested in this study is called TAK-500. The study will evaluate the safety, tolerability, antitumor activity, pharmacokinetics (PK), and pharmacodynamics 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 106 participants (approximately 72 in the Dose Escalation Phase and approximately 34 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 3 cohorts:
  • TAK-500 Single Agent (SA) (dosed Q3W)

  • Dose Escalation: TAK-500 (dosed Q3W) + Pembrolizumab (dosed Q3W)

  • Dose Expansion: TAK-500 (dosed Q3W and/or Q2W) + Pembrolizumab (dosed Q3W)

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

Study Design

Study Type:
Interventional
Anticipated Enrollment :
106 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Dose Escalation and Expansion, Phase 1a/1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics 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
Actual Study Start Date :
Apr 26, 2022
Anticipated Primary Completion Date :
Apr 8, 2025
Anticipated Study Completion Date :
Apr 8, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation: TAK-500 Single Agent (SA) (dosed Q3W)

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

Drug: TAK-500
TAK-500 intravenous infusion.

Experimental: Dose Escalation: TAK-500 (dosed Q3W) + Pembrolizumab (dosed Q3W)

TAK-500, infusion, intravenously, once on Day 1 of each 21-days treatment cycle (Q3W), along with pembrolizumab 200 milligram (mg) infusion, intravenously, once on Day 1 of each 21-days treatment 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: TAK-500
TAK-500 intravenous infusion.

Drug: Pembrolizumab
Pembrolizumab intravenous infusion.

Experimental: Dose Expansion: TAK-500 (dosed Q3W and/or Q2W) + Pembrolizumab (dosed Q3W)

TAK-500, infusion, intravenously, once on Days 1 and 22 (Q3W), and/or once on Days 1, 15, and 29, once every 2 weeks (Q2W), in a 42-days treatment cycle with pembrolizumab 200 mg infusion, intravenously, once on Days 1 and 22 (Q3W), in a 42-days treatment cycle for up to 1 year. The dose of TAK-500 for the Dose Expansion arm will be based on the results of the TAK-500 in combination with pembrolizumab Dose Escalation arm.

Drug: TAK-500
TAK-500 intravenous infusion.

Drug: Pembrolizumab
Pembrolizumab intravenous infusion.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Grade 3 or Higher TEAEs [Up to 30 months]

    TEAE Grades will be evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.

  2. Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) [Up to 30 months]

  3. Number of Participants With Dose Limiting Toxicities (DLTs) [Up to 30 months]

    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.

  4. Number of Participants Reporting one or More Serious Adverse Event (SAEs) [Up to 30 months]

  5. Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations [Up to 30 months]

Secondary Outcome Measures

  1. Pharmacologically Active Dose (PAD) range of TAK-500 SA and in Combination With Pembrolizumab [Cycle 1 (Cycle length is equal to [=] 21 [dose escalation] or 42 days [dose expansion])]

    PAD is defined as any dose at which there is pharmacodynamic evidence of TAK-500-mediated activation of the innate and adaptive immune system and/or clinical anti-tumor activity includes: confirmed partial response (cPR) or confirmed complete response (cCR) as determined by 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 millimeter (mm). Partial response (PR): defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.

  2. Recommended Phase 2 Dose (RP2D) of TAK-500 SA and in Combination With Pembrolizumab [Cycle 1 (Cycle length = 21 [dose escalation] or 42 days [dose expansion]]

  3. Cmax: Maximum Observed 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)]

  4. 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)]

  5. 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)]

  6. 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)]

  7. 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)]

  8. 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)]

  9. 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)]

  10. Overall Response Rate (ORR) [Up to 30 months]

    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.

  11. Disease Control Rate (DCR) [Up to 30 months]

    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.

  12. Duration of Response (DOR) [Up to 30 months]

    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.

  13. Time to Response (TTR) [Up to 30 months]

    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.

  14. Dose Expansion: Progression Free Survival (PFS) [Up to 30 months]

    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.

  15. Changes in Tumor Immune Cell Infiltration and Activation as Measured by Immunohistochemistry or In-Situ Hybridization [Up to 23 days after first administration of TAK-500]

    Measurement of changes in tumor immune cell infiltration and activation as 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.

  16. Changes in Tumor Immune Cell Activation as Measured by Gene Expression [Up to 23 days after first administration of TAK-500]

    Measurement of changes in interferon- and STING-related gene expression as measured from fresh tumor biopsies pre and post treatment (up to 23 days after first administration of TAK-500) for each participant.

  17. Number of Participants With Positive Anti-drug Antibody (ADA) and Acquired Immunogenicity [Up to 30 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 have 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, and triple-negative breast cancer (TNBC). Intolerant participants 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.

  3. Must have at least 1 RECIST version 1.1 evaluable lesion.

  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 <=3.0ULN or <=5.0ULN with liver metastases or HCC.

  • Albumin >=3.0 g/dL.

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

  • 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.

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

  2. 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.

  3. 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. Treated with other STING agonists/antagonists, Toll-like receptor agonists or CCR2 agonist/antagonist within the past 6 months.

  6. Active vaping within 90 days of C1D1 of study drug(s).

  7. Active smoking.

  8. 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.

  9. Grade >=2 fever of malignant origin.

  10. Chronic, active hepatitis (example, participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus [HCV] RNA).

  11. History of hepatic encephalopathy.

  12. Prior or current clinically significant ascites, as measured by physical examination, that requires active paracentesis for control.

  13. 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).

  14. 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.

  15. 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, and/or intra-articular corticosteroids.

  • Physiological doses of replacement steroid therapy (example, for adrenal insufficiency), not to exceed the equivalent of 10 mg prednisone daily.

  1. 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-ligand 1 antibody.

  2. History of intolerance to any component of the trial 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,

Contacts and Locations

Locations

Site City State Country Postal Code
1 City of Hope Duarte California United States 91010
2 University of California San Diego La Jolla California United States 92093-1503
3 University of Colorado - Anschutz Medical Campus - PPDS Aurora Colorado United States 80045
4 Sarah Cannon Research Institute Denver Colorado United States 80218-1238
5 Dana Farber Cancer Institute Boston Massachusetts United States 02215-5418
6 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111-2434
7 START South Texas Accelerated Research Therapeutics San Antonio Texas United States 78229-3307

Sponsors and Collaborators

  • Takeda

Investigators

  • Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT05070247
Other Study ID Numbers:
  • TAK-500-1001
First Posted:
Oct 7, 2021
Last Update Posted:
Aug 5, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
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
Keywords provided by Takeda
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 5, 2022