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A Study of Modakafusp Alfa (TAK-573) Given by Itself and Together With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors

Primary Purpose

Neoplasms, Melanoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Modakafusp Alfa
Pembrolizumab
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Neoplasms focused on measuring Drug Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  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:

  1. 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.
  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.

Sites / Locations

  • City of Hope Comprehensive Cancer Center - DuarteRecruiting
  • University of California San Diego Moores Cancer CenterRecruiting
  • The Angeles Clinic and Research Institute - West Los Angeles OfficeRecruiting
  • University of Colorado Health Memorial Hospital CentralRecruiting
  • Yale Cancer Center
  • Sylvester Comprehensive Cancer CenterRecruiting
  • Orlando Health Cancer InstituteRecruiting
  • HealthPartners Institute
  • Norris Cotton Cancer Center LebanonRecruiting
  • Morristown Medical CenterRecruiting
  • Cleveland Clinic Main CampusRecruiting
  • Fox Chase Cancer Center
  • University of Pittsburgh Medical CenterRecruiting
  • Avera Cancer InstituteRecruiting
  • Sarah Cannon Research InstituteRecruiting
  • Mary Crowley Cancer Research
  • Texas Oncology - Baylor Charles A. Sammons Cancer CenterRecruiting
  • NEXT Oncology
  • Intermountain Medical CenterRecruiting
  • West Virginia University Health Sciences CampusRecruiting
  • The Queen Elizabeth HospitalRecruiting
  • Ballarat Regional Integrated Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1b SA Dose Escalation

Phase 2 Safety Lead-in Dose Expansion: Modakafusp Alfa + Pembrolizumab

Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma With Primary Resistance)

Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma With Acquired Resistance)

Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma naïve to anti-PD1)

Arm Description

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.

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.

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.

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, 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.

Outcomes

Primary Outcome Measures

Phase 1b and Phase 2 Safety Lead-in: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs)
AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. A TEAE is 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 (90 days for immune-related adverse event [irAE]) of the last administration of study drug.
Phase 1b and Phase 2 Safety Lead-in: Number of Participants with Grade 3 or Higher TEAEs
TEAEs Grades will be evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0. (NCI CTCAE v5).
Phase 1b and Phase 2 Safety Lead-in: 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 modakafusp alfa. Toxicity will be evaluated according to NCI CTCAE v5.
Phase 1b and Phase 2 Safety Lead-in: Number of Participants Reporting one or More Serious Adverse Event (SAEs)
SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect or is considered to be an important medical event that may not result in death, be immediately life-threatening, or require hospitalization but may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant or may require medical or surgical intervention.
Phase 1b and Phase 2 Safety Lead-in: Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations
TEAE is 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 (90 days for irAE) of the last administration of study drug.
Phase 2 Expansion: Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) during the study in response-evaluable population. ORR will be assessed as per Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 for melanoma participants.

Secondary Outcome Measures

Phase 1b: Maximum Tolerated Dose (MTD) or Pharmacologically Active Dose (PAD)
Phase 1b and Phase 2 Safety Lead-in: Recommended Phase 2 Dose (RP2D) for Single Agent (SA) and in Combination With Pembrolizumab
The RP2D may be either MTD based on dose limiting toxicities or a pharmacologically active dose defined by the PK/pharmacodynamic model or exposure-response (ER) analysis in place.
Phase 2 Expansion: Number of Participants Reporting one or More TEAEs
TEAE is 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 (90 days for irAE) of the last administration of study drug.
Phase 2 Expansion: Number of Participants With Grade 3 or Higher TEAEs
TEAEs Grades will be evaluated as per the NCI CTCAE v5.
Phase 2 Expansion: Number of Participants Reporting one or More SAEs
SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect or is considered to be an important medical event that may not result in death, be immediately life-threatening, or require hospitalization but may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant or may require medical or surgical intervention.
Phase 2 Expansion: Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations
TEAE is 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 (90 days for irAE) of the last administration of study drug.
Phase 1b and Phase 2 Safety Lead-in: Cmax: Maximum Observed Serum Concentration for Modakafusp Alfa
Phase 1b and Phase 2 Safety Lead-in: Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for Modakafusp Alfa
Phase 1b and Phase 2 Safety Lead-in: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for Modakafusp Alfa
Phase 1b and Phase 2 Safety Lead-in: AUCinf: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Modakafusp Alfa
Phase 1b and Phase 2 Safety Lead-in: t1/2z: Terminal Disposition Phase Half-life for Modakafusp Alfa
Phase 1b and Phase 2 Safety Lead-in: CL: Total Clearance After Intravenous Administration for Modakafusp Alfa
Phase 1b and Phase 2 Safety Lead-in: Vss: Volume of Distribution at Steady State for Modakafusp Alfa
Phase 1b: Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieve CR or PR during the study in response-evaluable population. ORR will be assessed as per RECIST v1.1. for participants in dose escalation.
Phase 1b and Phase 2: Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieve CR, PR, or stable disease (SD) (determined by the investigator) during the study in response-evaluable population. The DCR will be assessed as per RECIST v1.1.
Phase 1b and Phase 2: Duration of Response (DOR)
DOR is the time from the date of first documentation of a PR or better to the date of first documentation of PD for responders (PR 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 v1.1.
Phase 1b and Phase 2: Time to Progression (TTP)
TTP is defined as the time from the date of the first dose of study drug to the date of the first documentation of PD according to RECIST v1.1.
Phase 1b and Phase 2: Progression Free Survival (PFS)
PFS is defined as the time from the date of the first dose of study drug to the date of first documentation of progressive disease according to RECIST v.1.1, or death due to any cause, whichever occurs first. Participants without documentation of PD or death will be censored at the date of the last response assessment that is SD or better.
Phase 1b and Phase 2: Overall Survival (OS)
OS is defined as the time from the date of first dose of study drug to the date of death due to any cause. Participants without documentation of death at the time of analysis will be censored at the date last known to be alive. OS will be assessed as per RECIST v1.1.
Phase 2 Expansion: ORR Based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
Phase 2 Expansion: DCR Based on iRECIST
Phase 2 Expansion: DOR Based on iRECIST
Phase 2 Expansion: TTP Based on iRECIST
Phase 2 Expansion: PFS Based on iRECIST
Phase 1b and Phase 2: Number of Participants With Anti-Modakafusp Alfa Antibodies
Phase 1b and Phase 2: Titer of Anti-Modakafusp Alfa Antibodies

Full Information

First Posted
November 6, 2019
Last Updated
October 19, 2023
Sponsor
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT04157517
Brief Title
A Study of Modakafusp Alfa (TAK-573) Given by Itself and Together With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 12, 2019 (Actual)
Primary Completion Date
January 24, 2024 (Anticipated)
Study Completion Date
January 24, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
The drug being tested in this study is called modakafusp alfa (TAK-573). Modakafusp alfa is being tested to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity as single agent (SA) or in combination with pembrolizumab in participants with locally advanced or metastatic solid tumors. The study will consist of 2 phases: Phase 1b dose escalation and a Phase 2 dose expansion. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Melanoma
Keywords
Drug Therapy

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
114 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1b SA Dose Escalation
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2 Safety Lead-in Dose Expansion: Modakafusp Alfa + Pembrolizumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma With Primary Resistance)
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma With Acquired Resistance)
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma naïve to anti-PD1)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Modakafusp Alfa
Other Intervention Name(s)
TAK-573
Intervention Description
Modakafusp alfa intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
Pembrolizumab intravenous infusion.
Primary Outcome Measure Information:
Title
Phase 1b and Phase 2 Safety Lead-in: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs)
Description
AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. A TEAE is 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 (90 days for immune-related adverse event [irAE]) of the last administration of study drug.
Time Frame
Up to 55 months
Title
Phase 1b and Phase 2 Safety Lead-in: Number of Participants with Grade 3 or Higher TEAEs
Description
TEAEs Grades will be evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0. (NCI CTCAE v5).
Time Frame
Up to 55 months
Title
Phase 1b and Phase 2 Safety Lead-in: Number of Participants With Dose Limiting Toxicities (DLTs)
Description
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 modakafusp alfa. Toxicity will be evaluated according to NCI CTCAE v5.
Time Frame
Cycle 1 (Cycle length is equal to [=] 21 days)
Title
Phase 1b and Phase 2 Safety Lead-in: Number of Participants Reporting one or More Serious Adverse Event (SAEs)
Description
SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect or is considered to be an important medical event that may not result in death, be immediately life-threatening, or require hospitalization but may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant or may require medical or surgical intervention.
Time Frame
Up to 55 months
Title
Phase 1b and Phase 2 Safety Lead-in: Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations
Description
TEAE is 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 (90 days for irAE) of the last administration of study drug.
Time Frame
Up to 55 months
Title
Phase 2 Expansion: Overall Response Rate (ORR)
Description
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) during the study in response-evaluable population. ORR will be assessed as per Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 for melanoma participants.
Time Frame
Up to 55 months
Secondary Outcome Measure Information:
Title
Phase 1b: Maximum Tolerated Dose (MTD) or Pharmacologically Active Dose (PAD)
Time Frame
Cycle 1 (Cycle length is equal to [=] 21 days)
Title
Phase 1b and Phase 2 Safety Lead-in: Recommended Phase 2 Dose (RP2D) for Single Agent (SA) and in Combination With Pembrolizumab
Description
The RP2D may be either MTD based on dose limiting toxicities or a pharmacologically active dose defined by the PK/pharmacodynamic model or exposure-response (ER) analysis in place.
Time Frame
Cycle 1 (Cycle length is equal to [=] 21 days)
Title
Phase 2 Expansion: Number of Participants Reporting one or More TEAEs
Description
TEAE is 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 (90 days for irAE) of the last administration of study drug.
Time Frame
Up to 55 months
Title
Phase 2 Expansion: Number of Participants With Grade 3 or Higher TEAEs
Description
TEAEs Grades will be evaluated as per the NCI CTCAE v5.
Time Frame
Up to 55 months
Title
Phase 2 Expansion: Number of Participants Reporting one or More SAEs
Description
SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect or is considered to be an important medical event that may not result in death, be immediately life-threatening, or require hospitalization but may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant or may require medical or surgical intervention.
Time Frame
Up to 55 months
Title
Phase 2 Expansion: Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations
Description
TEAE is 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 (90 days for irAE) of the last administration of study drug.
Time Frame
Up to 55 months
Title
Phase 1b and Phase 2 Safety Lead-in: Cmax: Maximum Observed Serum Concentration for Modakafusp Alfa
Time Frame
Phase 1b (Cycles 1-2) and Phase 2 (Cycle 1 and Cycle 3) Day 1: predose, at multiple timepoints (up to 72 hours (hrs) or up to 6 hrs (Phase 1b, Cycles 3-6) or up to 24 hrs (Phase 2, Cycle 2 and Cycle 4 onwards) postdose (cycle length=21 days)
Title
Phase 1b and Phase 2 Safety Lead-in: Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for Modakafusp Alfa
Time Frame
Phase 1b (Cycles 1-2) and Phase 2 (Cycle 1 and Cycle 3) Day 1: predose, at multiple timepoints (up to 72 hours (hrs) or up to 6 hrs (Phase 1b, Cycles 3-6) or up to 24 hrs (Phase 2, Cycle 2 and Cycle 4 onwards) postdose (cycle length=21 days)
Title
Phase 1b and Phase 2 Safety Lead-in: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for Modakafusp Alfa
Time Frame
Phase 1b (Cycles 1-2) and Phase 2 (Cycle 1 and Cycle 3) Day 1: predose, at multiple timepoints (up to 72 hours (hrs) or up to 6 hrs (Phase 1b, Cycles 3-6) or up to 24 hrs (Phase 2, Cycle 2 and Cycle 4 onwards) postdose (cycle length=21 days)
Title
Phase 1b and Phase 2 Safety Lead-in: AUCinf: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Modakafusp Alfa
Time Frame
Phase 1b (Cycles 1-2) and Phase 2 (Cycle 1 and Cycle 3) Day 1: predose, at multiple timepoints (up to 72 hours (hrs) or up to 6 hrs (Phase 1b, Cycles 3-6) or up to 24 hrs (Phase 2, Cycle 2 and Cycle 4 onwards) postdose (cycle length=21 days)
Title
Phase 1b and Phase 2 Safety Lead-in: t1/2z: Terminal Disposition Phase Half-life for Modakafusp Alfa
Time Frame
Phase 1b (Cycles 1-2) and Phase 2 (Cycle 1 and Cycle 3) Day 1: predose, at multiple timepoints (up to 72 hours (hrs) or up to 6 hrs (Phase 1b, Cycles 3-6) or up to 24 hrs (Phase 2, Cycle 2 and Cycle 4 onwards) postdose (cycle length=21 days)
Title
Phase 1b and Phase 2 Safety Lead-in: CL: Total Clearance After Intravenous Administration for Modakafusp Alfa
Time Frame
Phase 1b (Cycles 1-2) and Phase 2 (Cycle 1 and Cycle 3) Day 1: predose, at multiple timepoints (up to 72 hours (hrs) or up to 6 hrs (Phase 1b, Cycles 3-6) or up to 24 hrs (Phase 2, Cycle 2 and Cycle 4 onwards) postdose (cycle length=21 days)
Title
Phase 1b and Phase 2 Safety Lead-in: Vss: Volume of Distribution at Steady State for Modakafusp Alfa
Time Frame
Phase 1b (Cycles 1-2) and Phase 2 (Cycle 1 and Cycle 3) Day 1: predose, at multiple timepoints (up to 72 hours (hrs) or up to 6 hrs (Phase 1b, Cycles 3-6) or up to 24 hrs (Phase 2, Cycle 2 and Cycle 4 onwards) postdose (cycle length=21 days)
Title
Phase 1b: Overall Response Rate (ORR)
Description
ORR is defined as the percentage of participants who achieve CR or PR during the study in response-evaluable population. ORR will be assessed as per RECIST v1.1. for participants in dose escalation.
Time Frame
Up to 55 months
Title
Phase 1b and Phase 2: Disease Control Rate (DCR)
Description
DCR is defined as the percentage of participants who achieve CR, PR, or stable disease (SD) (determined by the investigator) during the study in response-evaluable population. The DCR will be assessed as per RECIST v1.1.
Time Frame
Up to 55 months
Title
Phase 1b and Phase 2: Duration of Response (DOR)
Description
DOR is the time from the date of first documentation of a PR or better to the date of first documentation of PD for responders (PR 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 v1.1.
Time Frame
Up to 55 months
Title
Phase 1b and Phase 2: Time to Progression (TTP)
Description
TTP is defined as the time from the date of the first dose of study drug to the date of the first documentation of PD according to RECIST v1.1.
Time Frame
Up to 55 months
Title
Phase 1b and Phase 2: Progression Free Survival (PFS)
Description
PFS is defined as the time from the date of the first dose of study drug to the date of first documentation of progressive disease according to RECIST v.1.1, or death due to any cause, whichever occurs first. Participants without documentation of PD or death will be censored at the date of the last response assessment that is SD or better.
Time Frame
Up to 55 months
Title
Phase 1b and Phase 2: Overall Survival (OS)
Description
OS is defined as the time from the date of first dose of study drug to the date of death due to any cause. Participants without documentation of death at the time of analysis will be censored at the date last known to be alive. OS will be assessed as per RECIST v1.1.
Time Frame
Up to 55 months
Title
Phase 2 Expansion: ORR Based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
Time Frame
Up to 55 months
Title
Phase 2 Expansion: DCR Based on iRECIST
Time Frame
Up to 55 months
Title
Phase 2 Expansion: DOR Based on iRECIST
Time Frame
Up to 55 months
Title
Phase 2 Expansion: TTP Based on iRECIST
Time Frame
Up to 55 months
Title
Phase 2 Expansion: PFS Based on iRECIST
Time Frame
Up to 55 months
Title
Phase 1b and Phase 2: Number of Participants With Anti-Modakafusp Alfa Antibodies
Time Frame
Up to 55 months
Title
Phase 1b and Phase 2: Titer of Anti-Modakafusp Alfa Antibodies
Time Frame
Up to 55 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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). Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Takeda Contact
Phone
+1-877-825-3327
Email
medinfoUS@takeda.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center - Duarte
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
626-218-9200
Email
yxing@coh.org
First Name & Middle Initial & Last Name & Degree
Yang Xing
Facility Name
University of California San Diego Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
858-552-7521
Email
gdaniels@health.ucsd.edu
First Name & Middle Initial & Last Name & Degree
Gregory Daniels
Facility Name
The Angeles Clinic and Research Institute - West Los Angeles Office
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
310-582-7900
Email
imehmi@theangelesclinic.org
First Name & Middle Initial & Last Name & Degree
Inderjit Mehmi
Facility Name
University of Colorado Health Memorial Hospital Central
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80909
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
719-304-4144
Email
robert.hoyer@uchealth.org
First Name & Middle Initial & Last Name & Degree
Robert Hoyer
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Individual Site Status
Completed
Facility Name
Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
305-284-2211
Email
jxl810@med.miami.edu
First Name & Middle Initial & Last Name & Degree
Jose Lutzky
Facility Name
Orlando Health Cancer Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
321-841-8470
Email
sajeve.thomas@orlandohealth.com
First Name & Middle Initial & Last Name & Degree
Sajeve Thomas
Facility Name
HealthPartners Institute
City
Bloomington
State/Province
Minnesota
ZIP/Postal Code
55425
Country
United States
Individual Site Status
Completed
Facility Name
Norris Cotton Cancer Center Lebanon
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
603-650-5534
Email
keisuke.shirai@hitchcock.org
First Name & Middle Initial & Last Name & Degree
Keisuke Shirai
Facility Name
Morristown Medical Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
973-971-6298
Email
eric.whitman@atlantichealth.org
First Name & Middle Initial & Last Name & Degree
Eric Whitman
Facility Name
Cleveland Clinic Main Campus
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
216-444-2273
Email
gastmab@ccf.org
First Name & Middle Initial & Last Name & Degree
Brian Gastman
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Individual Site Status
Completed
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
412-623-7707
Email
kirkwoodjm@upmc.edu
First Name & Middle Initial & Last Name & Degree
John Kirkwood
Facility Name
Avera Cancer Institute
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
605-322-6900
Email
heidi.mckean@avera.org
First Name & Middle Initial & Last Name & Degree
Heidi McKean
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
615-329-7274
Email
mmckean@tnonc.com
First Name & Middle Initial & Last Name & Degree
Meredith McKean
Facility Name
Mary Crowley Cancer Research
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Individual Site Status
Completed
Facility Name
Texas Oncology - Baylor Charles A. Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
214-370-1800
Email
lance.cowey@usoncology.com
First Name & Middle Initial & Last Name & Degree
Charles Cowey
Facility Name
NEXT Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78240
Country
United States
Individual Site Status
Completed
Facility Name
Intermountain Medical Center
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
801-507-3630
Email
david.gill@imail.org
First Name & Middle Initial & Last Name & Degree
David Gill
Facility Name
West Virginia University Health Sciences Campus
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
304-598-6984
Email
joanna.kolodney@hsc.wvu.edu
First Name & Middle Initial & Last Name & Degree
Joanna Kolodney
Facility Name
The Queen Elizabeth Hospital
City
Woodville South
State/Province
South Australia
ZIP/Postal Code
5011
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+614-0431-5188;+618-8463-2500
Email
rachel.roberts-thomson@sa.gov.au
First Name & Middle Initial & Last Name & Degree
Rachel Roberts-Thomson
Facility Name
Ballarat Regional Integrated Cancer Center
City
Ballarat
State/Province
Victoria
ZIP/Postal Code
3350
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
61353398000
Email
prashanth@ballaratoncology.com.au
First Name & Middle Initial & Last Name & Degree
Prashanth Prithviraj

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://vivli.org/ourmember/takeda/
Links:
URL
https://clinicaltrials.takeda.com/study-detail/5f6b603c4db2bf003ab4a367
Description
To obtain more information on the study, click here/on this link

Learn more about this trial

A Study of Modakafusp Alfa (TAK-573) Given by Itself and Together With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors

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