A Study of Modakafusp Alfa (TAK-573) Given by Itself and Together With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors
NCT ID: NCT04157517
Last Updated: 2024-12-27
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE1/PHASE2
45 participants
INTERVENTIONAL
2019-12-12
2023-12-20
Brief Summary
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The main aims of Phase 1b are:
* to check for side effects from modakafusp alfa in adults with locally advanced or metastatic solid tumors.
* to learn how much modakafusp alfa adults can receive without getting any major side effects from it.
The main aims of Phase 2 are:
* to check for side effects from modakafusp alfa when given together with pembrolizumab in adults with metastatic cutaneous melanoma which cannot be completely removed by surgery.
* to learn how these medicines improve their symptoms.
Participants will receive modakafusp alfa for up to 1 year (Phase 1b) or modakafusp alfa given together with pembrolizumab for up to 2 years (Phase 2). Those whose symptoms improve might continue treatment for longer.
In both phases of the study, participants will revisit the study clinic within 30 days after their last dose or before they start other cancer treatment, whichever happens first.
Detailed Description
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The study will enroll approximately 114 participants (approximately 30 participants in Phase 1b dose escalation phase; 3-9 participants in safety-lead in and 25 participants for each expansion cohort (3 cohorts) of Phase 2.
The dose escalation phase will enroll participants with solid tumors. The dose escalation phase is to evaluate SA recommended phase 2 dose (RP2D).
The dose expansion phase in combination with pembrolizumab will be initiated with a safety lead-in phase once the SA RP2D is determined for modakafusp alfa. The dose expansion will include participants with one of following 3 disease indications:
I. Unresectable/metastatic cutaneous melanoma with primary resistance to no more than 2 prior lines of anti-disease programmed cell death protein 1 (PD1) containing treatments in the metastatic setting.
II. Unresectable/metastatic cutaneous melanoma with acquired resistance to no more than 2 prior lines of anti-PD1 containing treatments in the metastatic setting.
III. Unresectable/metastatic cutaneous melanoma naïve to prior anti-PD1 containing treatments in the metastatic setting.
This multi-center trial will be conducted in the United States and Australia. Participants with demonstrated clinical benefit may continue treatment beyond 1 year for Phase 1b and 2 years for Phase 2 if approved by the sponsor. The overall time to participate in this study is 55 months. All participants will make an end of treatment (EOT) visit 30 days after receiving their last dose of study drug or before the start of subsequent systemic anticancer therapy, whichever occurs first for a safety follow up assessment.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
OTHER
NONE
Study Groups
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Phase 1b SA Dose Escalation
Modakafusp alfa 0.1 to 6 milligram per kilogram (mg/kg), infusion, intravenously, once on Day 1 of each 21-days treatment cycle for up to 1 year.
Modakafusp Alfa
Modakafusp alfa intravenous infusion.
Phase 2 Safety Lead-in Dose Expansion: Modakafusp Alfa + Pembrolizumab
Melanoma with primary resistance to prior anti-PD1, acquired resistance to prior anti-PD1 or naïve to anti-PD1.
Modakafusp alfa, infusion, intravenously, once on Day 1 of each 21-days treatment cycle and pembrolizumab 400 mg infusion, intravenously, once every 6 weeks for up to 2 years. The starting dose of modakafusp alfa for dose expansion safety lead-in phase will be the RP2D determined in the previous Phase 1b dose escalation phase.
Modakafusp Alfa
Modakafusp alfa intravenous infusion.
Pembrolizumab
Pembrolizumab intravenous infusion.
Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma With Primary Resistance)
Melanoma With Primary Resistance to prior anti-PD1. Modakafusp alfa, infusion, intravenously, once on Day 1 of each 21-days treatment cycle and pembrolizumab 400 mg infusion, intravenously, once every 6 weeks for up to 2 years, in participants with unresectable/metastatic cutaneous melanoma with primary resistance to no more than 2 prior lines of anti-PD1 containing treatments in the metastatic setting. The dose of modakafusp alfa for dose expansion phase will be the modakafusp alfa RP2D in combination with pembrolizumab determined in the previous Phase 2 dose expansion safety-lead in phase.
Modakafusp Alfa
Modakafusp alfa intravenous infusion.
Pembrolizumab
Pembrolizumab intravenous infusion.
Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma With Acquired Resistance)
Melanoma With Acquired Resistance to prior anti-PD1. Modakafusp alfa, infusion, intravenously, once on Day 1 of each 21-days treatment cycle and pembrolizumab 400 mg infusion, intravenously, once every 6 weeks for up to 2 years, in participants with unresectable/metastatic cutaneous melanoma with acquired resistance to no more than 2 prior lines of anti-PD1 containing treatments in the metastatic setting. The dose of modakafusp alfa for dose expansion phase will be the modakafusp alfa RP2D in combination with pembrolizumab determined in the previous Phase 2 dose expansion safety lead-in phase.
Modakafusp Alfa
Modakafusp alfa intravenous infusion.
Pembrolizumab
Pembrolizumab intravenous infusion.
Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma naïve to anti-PD1)
Modakafusp alfa, infusion, intravenously, once on Day 1 of each 21-days treatment cycle and pembrolizumab 400 mg infusion, intravenously, once every 6 weeks for up to 2 years, in participants with unresectable/metastatic cutaneous melanoma naive to prior line of anti-PD1 containing treatments in the metastatic setting. The dose of modakafusp alfa for dose expansion phase will be the modakafusp alfa RP2D in combination with pembrolizumab determined in the previous Phase 2 dose expansion safety lead-in phase.
Modakafusp Alfa
Modakafusp alfa intravenous infusion.
Pembrolizumab
Pembrolizumab intravenous infusion.
Interventions
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Modakafusp Alfa
Modakafusp alfa intravenous infusion.
Pembrolizumab
Pembrolizumab intravenous infusion.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. For both the dose escalation and expansion cohort phases of the study, eligible participants must have histologically confirmed advanced (locoregionally recurrent, not amenable to curative therapy) or metastatic solid tumors.
3. Measurable disease per RECIST v1.1. At least 1 target lesion amenable for biopsy is required for enrollment in phase 1b. A minimum of 1 target lesion for response assessment is required for enrollment in phase 2. A separate lesion amenable for biopsy is required for enrollment in phase 2 for cohorts I and II post futility analysis and for all participants (safety lead-in and expansion) with subgroup III melanoma.
4. Phase 1b Dose Escalation: Participants with histologically confirmed advanced locally (locoregionally recurrent, not amenable to curative therapy) or metastatic solid tumors.
Phase 2 Dose Expansion:
The combination cohorts, including participants in the safety-lead phase, will enroll participants with unresectable/metastatic melanoma in the following subgroups:
I. Unresectable/metastatic histologically confirmed cutaneous melanoma with primary resistance to no more than 2 prior lines of anti-PD1 containing treatments in the metastatic setting.
II. Unresectable/metastatic histologically confirmed cutaneous melanoma with acquired resistance to no more than 2 prior lines of anti-PD1 containing treatments in the metastatic setting.
III. Unresectable/metastatic histologically confirmed cutaneous melanoma naive to prior anti-PD1 containing treatments in the metastatic setting.
* Participants with BRAF V600E mutant melanoma may have received prior BRAF inhibitor therapy.
* For the expansion cohorts I and II, there is no limitation of total number of prior line(s) of therapy, but the number of prior line(s) containing anti-PD1 must be ≤2 in the metastatic setting.
* For the expansion cohort III, participants who received an anti-PD-1 treatment in the adjuvant setting must have completed that treatment at least 6 months prior to enrollment and must not have progressed on the anti-PD1 adjuvant treatment.
* Primary resistance is defined as a best response of PD or SD less than (\<) 6 months to an anti-PD1 alone or in combination with other agents (that is, CTLA4) in the initial anti-PD1 containing treatment.
* Acquired resistance is defined as a progression following a best response of CR, PR or SD\>6 months to a prior anti-PD1 alone or in combination with other agents (that is, CTLA4).
Exclusion Criteria
2. History of any of the following \<=6 months before first dose modakafusp alfa: New York Heart Association (NYHA) Grade III or IV congestive heart failure, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, any ongoing symptomatic cardiac arrhythmias of Grade \>2, pulmonary embolism, or symptomatic cerebrovascular events, or any other serious cardiac condition (example, symptomatic pericardial effusion or restrictive cardiomyopathy). Chronic, stable atrial fibrillation on stable anticoagulant therapy, including low molecular-weight heparin, is allowed.
3. Baseline QT interval with Fridericia's correction (QTcF) greater than (\>) 480 millisecond (msec) (Grade \>=2), history of congenital long QT syndrome, or torsades de pointes.
4. Patients with acral lentiginous melanoma are excluded in phase 2 except for the safety lead-in phase.
5. Ongoing or active infection.
6. Known history of human immunodeficiency virus (HIV) infection or any other relevant congenital or acquired immunodeficiency. Testing during screening period is required only if indicated by specific local regulations or investigator's criteria.
7. Known hepatitis B (HBV) surface antigen seropositive or detectable hepatitis C infection viral load. Note: Participants with a positive HBV core antibody can be enrolled but must have an undetectable hepatitis B viral load.
8. Autoimmune disease requiring systemic immunosuppressive therapy. Participants with immune mediated endocrine deficiency from previous therapy with stable hormone replacement are exceptions.
18 Years
ALL
No
Sponsors
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Takeda
INDUSTRY
Responsible Party
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Principal Investigators
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Study Director
Role: STUDY_DIRECTOR
Takeda
Locations
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City of Hope Comprehensive Cancer Center - Duarte
Duarte, California, United States
University of California San Diego Moores Cancer Center
La Jolla, California, United States
The Angeles Clinic and Research Institute - West Los Angeles Office
Los Angeles, California, United States
University of Colorado Health Memorial Hospital Central
Colorado Springs, Colorado, United States
Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Orlando Health Cancer Institute
Orlando, Florida, United States
Norris Cotton Cancer Center Lebanon
Lebanon, New Hampshire, United States
Morristown Medical Center
Morristown, New Jersey, United States
Cleveland Clinic Main Campus
Cleveland, Ohio, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Avera Cancer Institute
Sioux Falls, South Dakota, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, United States
Intermountain Medical Center
Murray, Utah, United States
West Virginia University Health Sciences Campus
Morgantown, West Virginia, United States
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia
Ballarat Regional Integrated Cancer Center
Ballarat, Victoria, Australia
Countries
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Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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To obtain more information on the study, click here/on this link
Other Identifiers
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U1111-1238-9163
Identifier Type: REGISTRY
Identifier Source: secondary_id
TAK-573-1001
Identifier Type: -
Identifier Source: org_study_id