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

Clinical Benefit Rate is defined by RECIST v1.1 as the percentage of participants with documented CR, PR, or stable disease (SD) since the date of treatment initiation. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR or PR must have been sustained a minimum of 28 days when confirmation was reported. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. SD must have been a minimum of 102 days from date of treatment initiation and documented on at least 2 consecutive post-baseline scans. Exact binomial confidence intervals (Clopper Pearson).

Time frame: Maximum duration of follow-up for CBR was 12.9 months.

Population: Efficacy Evaluable Population: all participants who had measurable disease at baseline, received at least one dose of study drug (telaglenastat or talazoparib), and completed at least one post-baseline tumor assessment, or discontinued study treatment early due to study drug-related toxicity or for disease-related death.

Overall Response Rate is defined by RECIST v1.1 as the percentage of participants with documented confirmed CR or confirmed PR since the date of treatment initiation. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR or PR must have been sustained a minimum of 28 days when confirmation was reported. Stable disease must have been a minimum of 51 days from date of treatment initiation. Exact binomial confidence intervals (Clopper Pearson).

Time frame: Maximum duration of follow-up for cORR was 12.9 months.

Population: Efficacy Evaluable Population: all participants who had measurable disease at baseline, received at least one dose of study drug (telaglenastat or talazoparib), and completed at least one post-baseline tumor assessment, or discontinued study treatment early due to study drug-related toxicity or for disease-related death.

A DLT was defined as an AE determined by the investigator to be possibly or probably related to study drug that also was: * Any ≥ Grade (Gr) 4 non-hematological toxicity * Gr 3 non-hematologic toxicity, except: fatigue; nausea/vomiting that responds within 24 hours after initiating maximal supportive care; rash or itching that resolves to ≤ Gr 1 within 2 weeks. * Any clinically meaningful Gr 3 non-hematologic laboratory value if medical intervention is required OR the abnormality leads to hospitalization, OR the abnormality persists for \> 1 week (except Gr 3/4 elevation in serum amylase and/or lipase not associated with clinical or radiological evidence of pancreatitis). * Gr ≥ 3 febrile neutropenia * Gr ≥ 4 anemia; neutropenia lasting \> 7 days; thrombocytopenia * Gr 3 thrombocytopenia associated with: a bleeding event that requires a platelet transfusion OR a life-threatening bleeding event occurring due to low platelet count which results in urgent intervention.

Time frame: During Cycle 1 on Days 1 through 28, inclusive

Population: DLT Evaluable Participants: All participants were considered DLT-evaluable, with the following exceptions: participants who withdrew or were withdrawn from the study prior to completing the DLT assessment window for any reason other than a DLT; participants who did not receive ≥ 75% of the assigned dose (depending on dose level) of telaglenastat and talazoparib, i.e., 42 doses of telaglenastat and 21 doses of talazoparib, in the first 28-day treatment cycle for any reason other than a DLT.

Hematology parameters conducted included red blood cell (RBC) count, hematocrit, hemoglobin, mean corpuscular volume (MCV), platelet count, white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, performed at the discretion of the investigator. Clinical chemistry parameters included aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, albumin, total protein, blood urea nitrogen (BUN), creatinine, sodium, potassium, chloride, calcium, carbon dioxide, glucose, and lactate dehydrogenase (LDH), performed at the discretion of the investigator.

Time frame: Hematology: screening, cycle 1 day 1, cycle 1 day 15, cycle 2 day 1, end of treatment (EOT). Clinical chemistry parameters: screening, cycle 1 day 1, cycle 1 day 8, cycle 1 day 15, cycle 1 day 22, cycle 2 day 1, cycle 2 day 15, EOT.

Population: Safety Analysis Set: all participants who received at least 1 dose of any study-specific treatment (telaglenastat or talazoparib).

AEs were grades as assessed by CTCAE v 5.0. A TEAE is defined as any AE occurring on or after the first dose of study drug, or existing events that worsened after the first dose during the study, up to 28 days after the last dose. An AE is considered related if the investigator assessed the relationship as possibly related or probably related. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression. Grade 5 disease progression events are excluded from this table.

Time frame: Start of treatment to 28 days post treatment; mean overall duration of talazoparib exposure was 88.7 days.

Population: Safety Analysis Set: all participants who received at least 1 dose of any study-specific treatment (telaglenastat or talazoparib).

ORR was defined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as the percentage of participants with documented complete response (CR) or partial response (PR) since the date of treatment initiation. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease must have been a minimum of 51 days from date of treatment initiation. Exact binomial confidence intervals (Clopper Pearson).

Time frame: Maximum duration of follow-up for ORR was 12.9 months.

Population: Efficacy Evaluable Population: all participants who had measurable disease at baseline, received at least one dose of study drug (telaglenastat or talazoparib), and completed at least one post-baseline tumor assessment, or discontinued study treatment early due to study drug-related toxicity or for disease-related death.

PFS was defined as the time from treatment initiation to the date of documented disease progression (PD) within 2 consecutive scheduled radiographic disease assessments or death for any cause, whichever occurs first. PD: ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition, the sum must also demonstrate an absolute increase of ≥ 5 mm. (The appearance of one or more new lesions is also considered progression). Participants with no documentation of PD or death on-study, PD or death occurs after missing 2 consecutive scheduled radiographic disease assessments, or new anti-cancer therapy were censored at the date of last available tumor assessment. Participants missing baseline disease assessments were censored at the date of first dose. Kaplan-Meier product-limit estimates. Brookmeyer-Crowley methodology for a non-parametric 95% CI was used.

Time frame: Maximum duration of follow-up for PFS was 12.9 months.

Population: Efficacy Evaluable Population: all participants who had measurable disease at baseline, received at least one dose of study drug (telaglenastat or talazoparib), and completed at least one post-baseline tumor assessment, or discontinued study treatment early due to study drug-related toxicity or for disease-related death.