Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors

This is a multicenter, open-label, dose-escalation and dose-expansion study. In Part 1,
escalating doses of CB-839 will be paired with the standard dose of talazoparib in order to
determine the maximum tolerated dose (MTD) and/or the RP2D of the regimen and to characterize
the safety and tolerability profile of the combination in participants with
advanced/metastatic solid tumors.

In Part 2, the combination of CB-839 and talazoparib will be evaluated at the RP2D determined
in Part 1 to evaluate the anti-cancer activity of the regimen in participants with
advanced/metastatic clear cell RCC, TNBC or CRC.

Inclusion Criteria:

(Part 1)

-Documented incurable/locally advanced or metastatic solid tumors that have either relapsed
or are refractory or intolerant to standard therapies of proven clinical benefit.

(Part 2) Meets 1 of the 3 defined cohorts:

- Cohort 1: Documented incurable/locally advanced or metastatic ccRCC

- Cohort 2: Documented incurable/locally advanced or metastatic TNBC defined as ER, PR
negative (<1%) and HER2 negative (immunohistochemistry 0 to 1+ or fluorescence in situ
hybridization [FISH] negative)

- Cohort 3: incurable/locally advanced or metastatic CRC

For both Parts 1 & 2:

- Recovery to baseline or ≤ Grade 1 CTCAE v.5.0 from toxicities related to the prior
therapy

- Adequate renal, hepatic, and hematological function

- Per RECIST v1.1 evaluable disease (Part 1) or measurable disease (Part 2)

- Ability to provide written consent in accordance with federal, local and institutional
guidelines

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

Exclusion Criteria for both Parts 1 & 2:

- Prior treatment with CB-839 or a PARP inhibitor

- Unable to received oral medications

- Active and/or untreated central nervous system metastasis. Patients with treated brain
metastases must have (1) documented radiographic stability of at least 4 weeks
duration demonstrated on baseline central nervous system (CNS) imaging prior to study
treatment and (2) be symptomatically stable and off steroids for at least 2 weeks
before administration of any study treatment.

- Major surgery within 28 days prior to first dose of study drug

- Receipt of any anticancer therapy within the following windows: small molecule
tyrosine kinase inhibitor therapy (including investigational) within the prior 2 weeks
or 5 half-lives prior to C1D1, whichever is longer; any type of anti-cancer antibody
or cytotoxic chemotherapy within 4 weeks prior to C1D1; radiation therapy for bone
metastasis within 2 weeks prior or any other external radiation therapy within 4 weeks
prior to C1D1; patients with clinically relevant ongoing complications from prior
radiation therapy are not eligible.