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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04157517




Registration number
NCT04157517
Ethics application status
Date submitted
6/11/2019
Date registered
8/11/2019

Titles & IDs
Public title
A Study of Modakafusp Alfa (TAK-573) Given by Itself and Together With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors
Scientific 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
Secondary ID [1] 0 0
U1111-1238-9163
Secondary ID [2] 0 0
TAK-573-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Modakafusp Alfa
Treatment: Drugs - Pembrolizumab

Experimental: 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.

Experimental: 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.

Experimental: 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.

Experimental: 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.

Experimental: 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.


Treatment: Drugs: Modakafusp Alfa
Modakafusp alfa intravenous infusion.

Treatment: Drugs: Pembrolizumab
Pembrolizumab intravenous infusion.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b and Phase 2 Safety Lead-in: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Up to 55 months
Primary outcome [2] 0 0
Phase 1b and Phase 2 Safety Lead-in: Number of Participants with Grade 3 or Higher TEAEs
Timepoint [2] 0 0
Up to 55 months
Primary outcome [3] 0 0
Phase 1b and Phase 2 Safety Lead-in: Number of Participants With Dose Limiting Toxicities (DLTs)
Timepoint [3] 0 0
Cycle 1 (Cycle length is equal to [=] 21 days)
Primary outcome [4] 0 0
Phase 1b and Phase 2 Safety Lead-in: Number of Participants Reporting one or More Serious Adverse Event (SAEs)
Timepoint [4] 0 0
Up to 55 months
Primary outcome [5] 0 0
Phase 1b and Phase 2 Safety Lead-in: Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations
Timepoint [5] 0 0
Up to 55 months
Primary outcome [6] 0 0
Phase 2 Expansion: Overall Response Rate (ORR)
Timepoint [6] 0 0
Up to 55 months
Secondary outcome [1] 0 0
Phase 1b: Maximum Tolerated Dose (MTD) or Pharmacologically Active Dose (PAD)
Timepoint [1] 0 0
Cycle 1 (Cycle length is equal to [=] 21 days)
Secondary outcome [2] 0 0
Phase 1b and Phase 2 Safety Lead-in: Recommended Phase 2 Dose (RP2D) for Single Agent (SA) and in Combination With Pembrolizumab
Timepoint [2] 0 0
Cycle 1 (Cycle length is equal to [=] 21 days)
Secondary outcome [3] 0 0
Phase 2 Expansion: Number of Participants Reporting one or More TEAEs
Timepoint [3] 0 0
Up to 55 months
Secondary outcome [4] 0 0
Phase 2 Expansion: Number of Participants With Grade 3 or Higher TEAEs
Timepoint [4] 0 0
Up to 55 months
Secondary outcome [5] 0 0
Phase 2 Expansion: Number of Participants Reporting one or More SAEs
Timepoint [5] 0 0
Up to 55 months
Secondary outcome [6] 0 0
Phase 2 Expansion: Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations
Timepoint [6] 0 0
Up to 55 months
Secondary outcome [7] 0 0
Phase 1b and Phase 2 Safety Lead-in: Cmax: Maximum Observed Serum Concentration for Modakafusp Alfa
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
Phase 1b and Phase 2 Safety Lead-in: Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for Modakafusp Alfa
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Phase 1b and Phase 2 Safety Lead-in: AUCinf: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Modakafusp Alfa
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Phase 1b and Phase 2 Safety Lead-in: t1/2z: Terminal Disposition Phase Half-life for Modakafusp Alfa
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
Phase 1b and Phase 2 Safety Lead-in: CL: Total Clearance After Intravenous Administration for Modakafusp Alfa
Timepoint [12] 0 0
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)
Secondary outcome [13] 0 0
Phase 1b and Phase 2 Safety Lead-in: Vss: Volume of Distribution at Steady State for Modakafusp Alfa
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Phase 1b: Overall Response Rate (ORR)
Timepoint [14] 0 0
Up to 55 months
Secondary outcome [15] 0 0
Phase 1b and Phase 2: Disease Control Rate (DCR)
Timepoint [15] 0 0
Up to 55 months
Secondary outcome [16] 0 0
Phase 1b and Phase 2: Duration of Response (DOR)
Timepoint [16] 0 0
Up to 55 months
Secondary outcome [17] 0 0
Phase 1b and Phase 2: Time to Progression (TTP)
Timepoint [17] 0 0
Up to 55 months
Secondary outcome [18] 0 0
Phase 1b and Phase 2: Progression Free Survival (PFS)
Timepoint [18] 0 0
Up to 55 months
Secondary outcome [19] 0 0
Phase 1b and Phase 2: Overall Survival (OS)
Timepoint [19] 0 0
Up to 55 months
Secondary outcome [20] 0 0
Phase 2 Expansion: ORR Based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
Timepoint [20] 0 0
Up to 55 months
Secondary outcome [21] 0 0
Phase 2 Expansion: DCR Based on iRECIST
Timepoint [21] 0 0
Up to 55 months
Secondary outcome [22] 0 0
Phase 2 Expansion: DOR Based on iRECIST
Timepoint [22] 0 0
Up to 55 months
Secondary outcome [23] 0 0
Phase 2 Expansion: TTP Based on iRECIST
Timepoint [23] 0 0
Up to 55 months
Secondary outcome [24] 0 0
Phase 2 Expansion: PFS Based on iRECIST
Timepoint [24] 0 0
Up to 55 months
Secondary outcome [25] 0 0
Phase 1b and Phase 2: Number of Participants With Anti-Modakafusp Alfa Antibodies
Timepoint [25] 0 0
Up to 55 months
Secondary outcome [26] 0 0
Phase 1b and Phase 2: Titer of Anti-Modakafusp Alfa Antibodies
Timepoint [26] 0 0
Up to 55 months

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Other
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [2] 0 0
Ballarat Regional Integrated Cancer Center - Ballarat
Recruitment postcode(s) [1] 0 0
5011 - Woodville South
Recruitment postcode(s) [2] 0 0
3350 - Ballarat
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
New Hampshire
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
South Dakota
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah
Country [12] 0 0
United States of America
State/province [12] 0 0
West Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Takeda
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.