Study Stopped
Study was terminated early due to futility.
A Study of Modakafusp Alfa (TAK-573) Given by Itself and Together With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors
An Open-Label, Dose-Escalation Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Modakafusp Alfa (TAK-573) as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Advanced or Metastatic Solid Tumors
2 other identifiers
interventional
45
2 countries
17
Brief Summary
This study has 2 phases. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Dec 2019
Longer than P75 for phase_1
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 6, 2019
CompletedFirst Posted
Study publicly available on registry
November 8, 2019
CompletedStudy Start
First participant enrolled
December 12, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 20, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 20, 2023
CompletedResults Posted
Study results publicly available
December 27, 2024
CompletedJanuary 29, 2026
January 1, 2026
4 years
November 6, 2019
November 4, 2024
January 12, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Phase 1b and Phase 2 Safety Lead-in: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. A TEAE was any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.
From signing of the informed consent form (ICF) through 30 days after last dose of study drug or the start of subsequent anticancer therapy, whichever occurred first (up to 1 year 1 month for Phase 1b and 2 years 1 month for Phase 2)
Phase 1b and Phase 2 Safety Lead-in: Number of Participants With Grade 3 or Higher TEAEs
TEAEs Grades were evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0. (NCI CTCAE v5), where Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL). Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
From signing of the ICF through 30 days after last dose of study drug or the start of subsequent anticancer therapy, whichever occurred first (up to 1 year 1 month for Phase 1b and 2 years 1 month for Phase 2)
Phase 1b and Phase 2 Safety Lead-in: Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was defined as any of the following AEs that occurred in the escalation phase or in the combination safety lead-in phase during Cycle 1 unless they were considered by the investigator to be clearly unrelated to therapy with modakafusp alfa according to NCI CTCAE version 5.0. Any Grade 5 TEAE. Febrile neutropenia: Grade \>=3 or 4 neutropenia. Grade 4 thrombocytopenia. Grade \>=3 thrombocytopenia. Any Grade 3 immune-related AEs such as pericarditis, pneumonitis, cardiotoxicity, hepatitis, or neurotoxicity. Delay in the initiation of Cycle 2 by more than 14 days from the calculated start date due to a lack of adequate recovery of treatment-related hematological or nonhematologic toxicities. Any Grade \>=3 nonhematologic toxicity with some exception. Any Grade 2 nonhematologic toxicity that was considered by the investigator to be related to study drug and dose-limiting.
Cycle 1 (Cycle length is equal to [=] 21 days)
Phase 1b and Phase 2 Safety Lead-in: Number of Participants Reporting One or More Serious Adverse Event (SAEs)
SAE was defined as any untoward medical occurrence that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of an existing hospitalization; resulted in persistent or significant disability or incapacity; was a congenital anomaly/birth defect; was a medically important event that might not result in death, be immediately life-threatening, or required hospitalization, but might be considered serious when, on the basis of appropriate medical judgment, it might jeopardize the participant, required medical or surgical intervention to prevent one of the outcomes listed above, or involves suspected transmission via a medicinal product of an infectious agent.
From signing of the ICF through 30 days after last dose of study drug even if the participants start non-protocol systemic therapy (up to 1 year 1 month for Phase 1b and 2 years 1 month for Phase 2)
Phase 1b and Phase 2 Safety Lead-in: Number of Participants With One or More TEAEs Leading to Dose Modifications and Treatment Discontinuations
TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.
From signing of the ICF through 30 days after last dose of study drug or the start of subsequent anticancer therapy, whichever occurred first (up to 1 year 1 month for Phase 1b and 2 years 1 month for Phase 2)
Phase 2 Expansion: Overall Response Rate (ORR) Based on RECIST v1.1
ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
From the first dose of study drug up to end of treatment or end of study (up to 2 years)
Secondary Outcomes (26)
Phase 1b: Maximum Tolerated Dose (MTD) of Modakafusp Alfa
Cycle 1 (Cycle length = 21 days)
Phase 1b and Phase 2 Safety Lead-in: Recommended Phase 2 Dose (RP2D) for Single Agent (SA) Modakafusp Alfa in Phase 1b and in Combination With Pembrolizumab in Phase 2 Safety Lead-in
Cycle 1 (Cycle length = 21 days)
Phase 2 Expansion: Number of Participants Reporting One or More TEAEs
From signing of the ICF through 30 days after last dose of study drug or the start of subsequent anticancer therapy, whichever occurred first (up to 2 years 1 month)
Phase 2 Expansion: Number of Participants With Grade 3 or Higher TEAEs
From signing of the ICF through 30 days after last dose of study drug or the start of subsequent anticancer therapy, whichever occurred first (up to 2 years 1 month)
Phase 2 Expansion: Number of Participants Reporting One or More SAEs
From signing of the ICF through 30 days after last dose of study drug even if the participants start non-protocol systemic therapy (up to 2 years 1 month)
- +21 more secondary outcomes
Study Arms (5)
Phase 1b SA Dose Escalation
EXPERIMENTALModakafusp 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.
Phase 2 Safety Lead-in Dose Expansion: Modakafusp Alfa + Pembrolizumab
EXPERIMENTALMelanoma 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.
Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma With Primary Resistance)
EXPERIMENTALMelanoma 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.
Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma With Acquired Resistance)
EXPERIMENTALMelanoma 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.
Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma naïve to anti-PD1)
EXPERIMENTALModakafusp 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.
Interventions
Modakafusp alfa intravenous infusion.
Pembrolizumab intravenous infusion.
Eligibility Criteria
You may qualify if:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- 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.
- 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.
- 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).
You may not qualify if:
- Persistent toxicity from previous treatments that has not resolved to less than or equal to (\<=) CTCAE version 5.0 Grade 1 prior to administration of modakafusp alfa, except for alopecia, Grade 2 neuropathy, and Grade 2 asthenia/fatigue, or autoimmune endocrinopathies with stable replacement therapy.
- 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.
- 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.
- Patients with acral lentiginous melanoma are excluded in phase 2 except for the safety lead-in phase.
- Ongoing or active infection.
- 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.
- 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.
- Autoimmune disease requiring systemic immunosuppressive therapy. Participants with immune mediated endocrine deficiency from previous therapy with stable hormone replacement are exceptions.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
City of Hope Comprehensive Cancer Center - Duarte
Duarte, California, 91010, United States
University of California San Diego Moores Cancer Center
La Jolla, California, 92093, United States
The Angeles Clinic and Research Institute - West Los Angeles Office
Los Angeles, California, 90025, United States
University of Colorado Health Memorial Hospital Central
Colorado Springs, Colorado, 80909, United States
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136, United States
Orlando Health Cancer Institute
Orlando, Florida, 32806, United States
Norris Cotton Cancer Center Lebanon
Lebanon, New Hampshire, 03756, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Cleveland Clinic Main Campus
Cleveland, Ohio, 44195, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232, United States
Avera Cancer Institute
Sioux Falls, South Dakota, 57105, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246, United States
Intermountain Medical Center
Murray, Utah, 84107, United States
West Virginia University Health Sciences Campus
Morgantown, West Virginia, 26506, United States
The Queen Elizabeth Hospital
Woodville South, South Australia, 5011, Australia
Ballarat Regional Integrated Cancer Center
Ballarat, Victoria, 3350, Australia
Related Publications (1)
Gill D, Cowey CL, Daniels GA, Sommerhalder D, Abdul-Karim R, Kirkwood JM, Kolodney J, Mehmi I, Roberts-Thomson R, Strauss J, Thomas S, Whitman E, Xing Y, McKean M, Collins S, Li C, Saggu G, Chen T, Wang S, Lewis M, Parot X, Johnson M. A phase Ib/II study of modakafusp alfa alone and in combination with pembrolizumab in patients with advanced or metastatic solid tumors. Front Oncol. 2025 Dec 8;15:1620987. doi: 10.3389/fonc.2025.1620987. eCollection 2025.
PMID: 41445795DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Study was terminated early due to futility.
Results Point of Contact
- Title
- Study Director
- Organization
- Teva Branded Pharmaceutical Products R&D LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 6, 2019
First Posted
November 8, 2019
Study Start
December 12, 2019
Primary Completion
December 20, 2023
Study Completion
December 20, 2023
Last Updated
January 29, 2026
Results First Posted
December 27, 2024
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be assessed for scientific merit, product approval status, and conflicts of interest. If the request is approved, patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please visit USMedInfo@tevapharm.com to make your request.