Key
Inclusion Criteria:
- - Written informed consent.
- - Cytologically or histologically confirmed locally advanced or metastatic solid tumor
that has progressed on standard therapy or for which no standard therapy exist; or
be intolerant of standard therapy.
- - Have not received an experimental drug within 4 weeks or 5 half-lives (whichever is
shorter) of study drug treatment or already be enrolled in a clinical study.
- - ECOG performance status 0-1.
- - Laboratory and ECG assessments within 28 days of enrollment including acceptable
cardiac, renal, and hepatic functions.
- - Agree to baseline core needle biopsy or archival (within 12 months of screening)
tumor submission; Note: Participants whose only site(s) of disease are in areas
considered moderate or high risk for biopsy complications may be enrolled without a
fresh biopsy upon Sponsor approval.
- - Non pregnant participants; female participants of child bearing potential with
non-sterile partners agree to use an effective form of contraception from the time
of first dose of study drug (or 14 days prior to first dose for oral contraception)
until 7 months after the last dose of study drug.
Effective forms of contraception
include hormonal (injection or oral), double barrier method, or intrauterine device.
Non-sterile male participants with sexual partners of childbearing potential agree
to use a barrier contraception method and agree to not donate sperm from the time of
first dose of study drug until 4 months after the last dose of study drug.
- - Measurable disease according to Response Evaluation Criteria in Solid Tumors
(RECIST) version (v)1.1.
Phase 1 Expansion Cohorts Specific Inclusion Criteria (in addition to above inclusion
criteria):
- - NSCLC: Participants must have locally advanced/unresectable or metastatic NSCLC.
Participants must have received ≤2 prior lines of therapy in the advanced/metastatic
setting.
- - TNBC: Participants must have locally advanced unresectable, recurrent, or metastatic
TNBC.
Participants must have received ≤2 prior lines of therapy in the
advanced/metastatic setting. TNBC participants with germline BRCA1/2 mutations must
have received ≤3 prior lines of therapy in the advanced/metastatic setting.
- - Ovarian Cancer: Participants must have locally advanced unresectable, recurrent, or
metastatic ovarian cancer.
Participants must have received ≤2 prior lines of therapy
in the advanced/metastatic setting with or without maintenance treatment.
- - Tumors with AKT3 mutation/amplification: Participants must have a locally advanced
unresectable, recurrent, or metastatic solid malignancy.
Participants with known
AKT3 mutation/amplification based on next generation sequencing (NGS) performed per
local standard of care.
Phase 2 Specific Inclusion Criteria (in addition to above inclusion criteria):
- - Have confirmed unresectable Stage III or metastatic Stage IV cutaneous melanoma that
has radiographically progressed (as confirmed by imaging assessed by the
Investigator) on an approved first-line single-agent or combination anti-PD-1
therapy.
- - Receiving anti-PD-1 therapy as their first line of treatment at the time of
enrollment and amenable to continuing anti-PD-1 therapy during the study.
Key
Exclusion Criteria:
- - Ongoing >Grade 1 toxicity from prior therapy according to Common Terminology
Criteria for Adverse Events v5.0 (Note: Grade 2 alopecia and Grade 2 sensory
neuropathy are not exclusionary)
- Has melanoma with documented BRAF mutation (Phase 2 only)
- Has known leptomeningeal disease, spinal cord compression, or brain metastases,
except participants with the following:
- Brain metastases that have been treated and are clinically stable for at least
4 weeks prior to the first administration of study drug; Note: Participants
receiving steroids for brain metastases must be either off steroids or on a
stable, or decreasing dose, of <10 mg daily of prednisone (or equivalent) in
order to be eligible for enrollment; and.
- - No ongoing neurological symptoms related to the anatomic location of the brain
metastases.
Note: Neurological symptoms that are considered sequelae to treatment for brain
metastases are allowed.
- - Has known structural cardiac disease.
- - Has known serious arrythmia, serious dysrhythmia, history of long QT syndrome, or
clinically relevant cardiac conduction abnormalities.
- - Has an active autoimmune disease that has required systemic treatment in the past 2
years (ie, with use of disease modifying agents, corticosteroids, or
immunosuppressive drugs).
Replacement therapy (eg, thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed.
- - At time of screening, is receiving systemic steroid therapy (greater than or equal
to 10 mg/day of prednisone or equivalent) or is taking any immunosuppressive
therapy; Note: Use of topical, inhaled, nasal, or ophthalmic steroids is allowed.
- - Has active and clinically significant bacterial, fungal, or viral infection,
including known hepatitis B virus (HBV), hepatitis C virus (HCV), or human
immunodeficiency virus (HIV)
- Has a history of, or currently has, an acquired or primary (congenital)
immunodeficiency;
- Has had prior anti-cancer treatment with chemotherapeutic agents or immune
modulating agents within <4 weeks or 5 half-lives, whichever is shorter, prior to
the first dose of study drug.
- - Has received a live vaccine within 30 days of first dose of study drug;
- Has had or has planned major surgery within 2 weeks of the first dose of study drug;
- Inability to swallow an oral dose of a medication (eg, oral capsules)
- Is taking medications that are considered strong inducers or inhibitors of CYP2C8 or
CYP3A4/5, P-glycoprotein (P-gp), breast cancer resistant protein (BCRP), or
sensitive substrates of P-gp and BCRP (Appendix C) that cannot be discontinued at
least 1 week prior to first dose of study drug and for the duration of the study.
- - Is taking drugs that modify gastric pH, such as proton-pump inhibitors (PPIs) or H2
blockers.
Antacids such as calcium carbonate or aluminum hydroxide-based products
are permitted.
