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

  • STATUS
    Recruiting
  • End date
    Aug 2, 2023
  • participants needed
    114
  • sponsor
    Takeda
Updated on 19 September 2022
metastatic melanoma
cancer
androgens
measurable disease
melanoma skin
treatment regimen
BRAF
pembrolizumab
bone scan
prostate specific antigen
abiraterone
orchiectomy
enzalutamide
castration-resistant prostate cancer
cancer treatment
primary cancer
adenocarcinoma
solid tumour
solid tumor
bisphosphonate
braf inhibitor
taxane
immunomodulator
pdac
immunostimulants
neck cancer
immunomodulators
immunologic adjuvant
malignant melanoma of skin
braf v600e mutation
metastatic cutaneous melanoma
denosumab therapy
bilateral orchidectomy
diphosphonates

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.

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.

Details
Condition Neoplasms, Melanoma
Treatment Pembrolizumab, TAK-573, Modakafusp Alfa
Clinical Study IdentifierNCT04157517
SponsorTakeda
Last Modified on19 September 2022

Eligibility

Yes No Not Sure

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 mRECIST 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, the initiation of treatment in the current study
should be within the 12 months of the completion of the last anti-PD1 containing
treatment
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

Ongoing or active infection
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
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
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
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