This study has 2 phases.
The main aims of Phase 1b are:
- to check for side effects from TAK-573 in adults with locally advanced or metastatic
solid tumors.
- to learn how much TAK-573 adults can receive without getting any major side effects from
it.
The main aims of Phase 2 are:
- to check for side effects from TAK-573 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 TAK-573 for up to 1 year (Phase 1b) or TAK-573 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.
The drug being tested in this study is called TAK-573. TAK-573 is being tested to evaluate
the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics 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 dose
escalation phase; 3-9 participants in safety-lead in and 25 participants for each expansion
cohort (3 cohorts).
The dose escalation phase will enroll participants with solid tumors. The dose escalation
phase is to evaluate SA RP2D.
The dose expansion phase will be initiated with a safety lead-in phase once the SA RP2D is
determined for TAK-573. 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-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. 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.
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 mRECIST v.1.1. At least one target lesion amenable for biopsy
is required for enrollment in the phase 1b, and a minimum of 2 target lesions is
required for enrollment in the phase 2 (one for biopsy and at least one for response
assessment).
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, 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:
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 TAK-573, except for
alopecia, Grade 2 neuropathy, and Grade 2 asthenia/fatigue.
2. History of any of the following <=6 months before first dose: 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. Ongoing or active infection.
5. 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.
6. Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C
infection viral load. Testing during screening period is required only if indicated by
local regulations or investigator's criteria.
7. Autoimmune disease requiring systemic immunosuppressive therapy. Participants with
immune mediated endocrine deficiency from previous therapy with stable hormone
replacement are exceptions.
