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

• Sponsor: Calithera Biosciences, Inc (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03875313
• Collaborator: (none)
• Enrollment: 33
• Locations: 9
• Arms: 5
• Actual Duration (Months): 14.3
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a Phase 1b/2 study to determine the recommended phase 2 dose (RP2D), safety and tolerability, pharmacokinetics (PK) and clinical activity of the glutaminase inhibitor CB-839 with the poly adenosine diphosphate ribose polymerase (PARP) inhibitor talazoparib in participants with advanced/metastatic solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor; Clear Cell Renal Cell Carcinoma; TNBC - Triple-Negative Breast Cancer; Colorectal Cancer; CRC; RCC; ccRCC	Drug: CB-839; Drug: Talazoparib	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b/2 Open Label, Dose Escalation and Expansion Study of the Glutaminase Inhibitor CB-839 in Combination With the PARP Inhibitor Talazoparib in Patients With Advanced or Metastatic Solid Tumors
• Actual Study Start Date: May 20, 2019
• Actual Primary Completion Date: Jul 29, 2020
• Actual Study Completion Date: Jul 29, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 600 mg CB-839 + 1 mg Talazoparib 600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.	Drug: CB-839; CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.; Other Names: telaglenastat ; Drug: Talazoparib; Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.; Other Names: Talzenna
Experimental: 800 mg CB-839 + 1 mg Talazoparib: ccRCC 800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received ≥ 2 prior systemic regimens including ≥ 1 vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) therapy.	Drug: CB-839; CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.; Other Names: telaglenastat ; Drug: Talazoparib; Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.; Other Names: Talzenna
Experimental: 800 mg CB-839 + 1 mg Talazoparib: TNBC 800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic triple-negative breast cancer (TNBC) estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior poly adenosine diphosphate ribose polymerase (PARP) inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.	Drug: CB-839; CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.; Other Names: telaglenastat ; Drug: Talazoparib; Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.; Other Names: Talzenna
Experimental: 800 mg CB-839 + 1 mg Talazoparib: CRC 800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic colorectal cancer (CRC) who received appropriate oxaliplatin or irinotecan- and fluorouracil (5-FU)-based chemotherapy with or without bevacizumab.	Drug: CB-839; CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.; Other Names: telaglenastat ; Drug: Talazoparib; Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.; Other Names: Talzenna
Experimental: 800 mg CB-839 + 1 mg Talazoparib: Other Histology 800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).	Drug: CB-839; CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.; Other Names: telaglenastat ; Drug: Talazoparib; Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.; Other Names: Talzenna

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Excluding Deaths Due to Disease Progression [Start of treatment to 28 days post treatment; mean overall duration of talazoparib exposure was 88.7 days.]

   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.

2. Number of Participants With Laboratory Abnormalities (Hematology, Clinical Chemistry) at More Than 1 Clinic Visit [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.]

   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.

3. Number of Participants With Dose-Limiting Toxicities (DLTs) [During Cycle 1 on Days 1 through 28, inclusive]

   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.

4. Overall Response Rate (ORR) [Maximum duration of follow-up for ORR was 12.9 months.]

   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).

5. Confirmed ORR (cORR) [Maximum duration of follow-up for cORR was 12.9 months.]

   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).

6. Clinical Benefit Rate (CBR) [Maximum duration of follow-up for CBR was 12.9 months.]

   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).

7. Progression-Free Survival (PFS) [Maximum duration of follow-up for PFS was 12.9 months.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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 Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 from toxicities related to the prior therapy

• Adequate renal, hepatic, and hematological function

• Per Response Evaluation Criteria in Solid Tumours (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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35294
2	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
3	University of Iowa	Iowa City	Iowa	United States	52242
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	Columbia University	New York	New York	United States	10032
6	MD Anderson	Houston	Texas	United States	77030
7	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas	United States	78229
8	Huntsman Cancer Institute	Salt Lake City	Utah	United States	20000
9	University of Wisconsin	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Calithera Biosciences, Inc

Investigators

• Study Director: Sam Whiting, MD, PhD, Calithera Biosciences, Inc

Study Documents (Full-Text)

• Study Protocol - Apr 10, 2019
• Statistical Analysis Plan - Sep 10, 2020

More Information

Publications

None provided.

• Responsible Party: Calithera Biosciences, Inc
• ClinicalTrials.gov Identifier: NCT03875313
• Other Study ID Numbers: CX-839-011
• First Posted: Mar 14, 2019
• Last Update Posted: Feb 17, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Calithera Biosciences, Inc: Tumor Metabolism; Glutaminase Inhibitor; CB-839; telaglenastat; talazoparib; PARP Inhibitor; DNA Damage; DNA Repair; Homologous recombination deficiency; HRD; BRCA 1; BRCA 2
• Additional relevant MeSH terms: Carcinoma, Renal Cell; Triple Negative Breast Neoplasms; Talazoparib

Study Results

Participant Flow

Arm/Group Title	600 mg CB-839 + 1 mg Talazoparib	800 mg CB-839 + 1 mg Talazoparib: ccRCC	800 mg CB-839 + 1 mg Talazoparib: TNBC	800 mg CB-839 + 1 mg Talazoparib: CRC	800 mg CB-839 + 1 mg Talazoparib: Other Histology
Arm/Group Description	600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received ≥ 2 prior systemic regimens including ≥ 1 vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) therapy.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic triple-negative breast cancer (TNBC) estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-negativewho received ≥ 1 prior line of cytotoxic chemotherapy with no prior poly adenosine diphosphate ribose polymerase (PARP) inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic colorectal cancer (CRC) who received appropriate oxaliplatin or irinotecan- and fluorouracil (5-FU)-based chemotherapy with or without bevacizumab.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).
Period Title: Overall Study
STARTED	3	16	6	4	4
COMPLETED	0	0	0	0	0
NOT COMPLETED	3	16	6	4	4

Baseline Characteristics

Arm/Group Title	600 mg CB-839 + 1 mg Talazoparib	800 mg CB-839 + 1 mg Talazoparib: ccRCC	800 mg CB-839 + 1 mg Talazoparib: TNBC	800 mg CB-839 + 1 mg Talazoparib: CRC	800 mg CB-839 + 1 mg Talazoparib: Other Histology	Total
Arm/Group Description	600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic ccRCC who received ≥ 2 prior systemic regimens including ≥ 1 VEGFR TKI therapy.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic TNBC ER-, PR-, and HER2-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior PARP inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic CRC who received appropriate oxaliplatin or irinotecan- and 5-FU-based chemotherapy with or without bevacizumab.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).	Total of all reporting groups
Overall Participants	3	16	6	4	4	33
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (10.00)	60.8 (10.58)	51.3 (13.19)	55.5 (10.66)	59.0 (11.69)	58.5 (11.21)
Sex: Female, Male (Count of Participants)
Female	0 0%	6 37.5%	6 100%	2 50%	2 50%	16 48.5%
Male	3 100%	10 62.5%	0 0%	2 50%	2 50%	17 51.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 12.5%	0 0%	1 25%	0 0%	3 9.1%
Not Hispanic or Latino	3 100%	13 81.3%	6 100%	3 75%	4 100%	29 87.9%
Unknown or Not Reported	0 0%	1 6.3%	0 0%	0 0%	0 0%	1 3%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	1 6.3%	0 0%	0 0%	0 0%	1 3%
Asian	1 33.3%	1 6.3%	0 0%	0 0%	0 0%	2 6.1%
Black or African American	0 0%	1 6.3%	2 33.3%	0 0%	1 25%	4 12.1%
White	2 66.7%	13 81.3%	3 50%	4 100%	3 75%	25 75.8%
Other, Not Specified	0 0%	0 0%	1 16.7%	0 0%	0 0%	1 3%
Not Reported	0 0%	1 6.3%	0 0%	0 0%	0 0%	1 3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Excluding Deaths Due to Disease Progression
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	600 mg CB-839 + 1 mg Talazoparib	800 mg CB-839 + 1 mg Talazoparib: ccRCC	800 mg CB-839 + 1 mg Talazoparib: TNBC	800 mg CB-839 + 1 mg Talazoparib: CRC	800 mg CB-839 + 1 mg Talazoparib: Other Histology
Arm/Group Description	600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic ccRCC who received ≥ 2 prior systemic regimens including ≥ 1 VEGFR TKI therapy.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic TNBC ER-, PR-, and HER2-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior PARP inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic CRC who received appropriate oxaliplatin or irinotecan- and 5-FU-based chemotherapy with or without bevacizumab.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).
Measure Participants	3	16	6	4	4
AE	3 100%	16 100%	6 100%	3 75%	4 100%
AE grade ≥ 3	1 33.3%	12 75%	3 50%	0 0%	3 75%
AE related to telaglenastat	3 100%	14 87.5%	6 100%	2 50%	3 75%
AE related to talazoparib	3 100%	16 100%	6 100%	2 50%	3 75%
AE related to telaglenastat and talazoparib	3 100%	11 68.8%	6 100%	2 50%	3 75%
AE grade ≥ 3 related to telaglenastat	1 33.3%	4 25%	2 33.3%	0 0%	1 25%
AE grade ≥ 3 related to talazoparib	1 33.3%	11 68.8%	2 33.3%	0 0%	2 50%
AE leading to discontinuation of telaglenastat	0 0%	0 0%	0 0%	0 0%	1 25%
AE leading to discontinuation of talazoparib	0 0%	0 0%	0 0%	0 0%	1 25%
AE leading to discontinuation of telaglenastat and talazoparib	0 0%	0 0%	0 0%	0 0%	1 25%
AE leading to discontinuation of telaglenastat or talazoparib	0 0%	0 0%	0 0%	0 0%	1 25%
AE leading to telaglenastat dose interruption or reduction	0 0%	10 62.5%	3 50%	0 0%	4 100%
AE leading to talazoparib dose interruption or reduction	1 33.3%	12 75%	3 50%	0 0%	4 100%
AE leading to telaglenastat and talazoparib dose interruption or reduction	0 0%	9 56.3%	3 50%	0 0%	4 100%
AE leading to telaglenastat or talazoparib dose interruption or reduction	1 33.3%	12 75%	3 50%	0 0%	4 100%
SAE with CTCAE grade 5	0 0%	0 0%	0 0%	0 0%	0 0%
SAE with CTCAE grade 5 related to telaglenastat	0 0%	0 0%	0 0%	0 0%	0 0%
SAE with CTCAE grade 5 related to talazoparib	0 0%	0 0%	0 0%	0 0%	0 0%
SAE	0 0%	2 12.5%	1 16.7%	0 0%	3 75%
SAE grade ≥ 3	0 0%	2 12.5%	1 16.7%	0 0%	3 75%
SAE related to telaglenastat	0 0%	2 12.5%	0 0%	0 0%	0 0%
SAE related to talazoparib	0 0%	2 12.5%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Laboratory Abnormalities (Hematology, Clinical Chemistry) at More Than 1 Clinic Visit
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	600 mg CB-839 + 1 mg Talazoparib	800 mg CB-839 + 1 mg Talazoparib: ccRCC	800 mg CB-839 + 1 mg Talazoparib: TNBC	800 mg CB-839 + 1 mg Talazoparib: CRC	800 mg CB-839 + 1 mg Talazoparib: Other Histology
Arm/Group Description	600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic ccRCC who received ≥ 2 prior systemic regimens including ≥ 1 VEGFR TKI therapy.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic TNBC ER-, PR-, and HER2-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior PARP inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic CRC who received appropriate oxaliplatin or irinotecan- and 5-FU-based chemotherapy with or without bevacizumab.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).
Measure Participants	3	16	6	4	4
Hematology	0 0%	0 0%	0 0%	0 0%	0 0%
Clinical Chemistry	0 0%	0 0%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants With Dose-Limiting Toxicities (DLTs)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	600 mg CB-839 + 1 mg Talazoparib	800 mg CB-839 + 1 mg Talazoparib: ccRCC	800 mg CB-839 + 1 mg Talazoparib: TNBC	800 mg CB-839 + 1 mg Talazoparib: CRC	800 mg CB-839 + 1 mg Talazoparib: Other Histology
Arm/Group Description	600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic ccRCC who received ≥ 2 prior systemic regimens including ≥ 1 VEGFR TKI therapy.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic TNBC ER-, PR-, and HER2-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior PARP inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic CRC who received appropriate oxaliplatin or irinotecan- and 5-FU-based chemotherapy with or without bevacizumab.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).
Measure Participants	3	16	6	4	4
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Overall Response Rate (ORR)
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	600 mg CB-839 + 1 mg Talazoparib	800 mg CB-839 + 1 mg Talazoparib: ccRCC	800 mg CB-839 + 1 mg Talazoparib: TNBC	800 mg CB-839 + 1 mg Talazoparib: CRC	800 mg CB-839 + 1 mg Talazoparib: Other Histology
Arm/Group Description	600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic ccRCC who received ≥ 2 prior systemic regimens including ≥ 1 VEGFR TKI therapy.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic TNBC ER-, PR-, and HER2-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior PARP inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic CRC who received appropriate oxaliplatin or irinotecan- and 5-FU-based chemotherapy with or without bevacizumab.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).
Measure Participants	2	15	5	4	3
Number (95% Confidence Interval) [percentage of participants]	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%

5. Primary Outcome

Title	Confirmed ORR (cORR)
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	600 mg CB-839 + 1 mg Talazoparib	800 mg CB-839 + 1 mg Talazoparib: ccRCC	800 mg CB-839 + 1 mg Talazoparib: TNBC	800 mg CB-839 + 1 mg Talazoparib: CRC	800 mg CB-839 + 1 mg Talazoparib: Other Histology
Arm/Group Description	600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic ccRCC who received ≥ 2 prior systemic regimens including ≥ 1 VEGFR TKI therapy.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic TNBC ER-, PR-, and HER2-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior PARP inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic CRC who received appropriate oxaliplatin or irinotecan- and 5-FU-based chemotherapy with or without bevacizumab.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).
Measure Participants	2	15	5	4	3
Number (95% Confidence Interval) [percentage of participants]	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%

6. Primary Outcome

Title	Clinical Benefit Rate (CBR)
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	600 mg CB-839 + 1 mg Talazoparib	800 mg CB-839 + 1 mg Talazoparib: ccRCC	800 mg CB-839 + 1 mg Talazoparib: TNBC	800 mg CB-839 + 1 mg Talazoparib: CRC	800 mg CB-839 + 1 mg Talazoparib: Other Histology
Arm/Group Description	600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic ccRCC who received ≥ 2 prior systemic regimens including ≥ 1 VEGFR TKI therapy.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic TNBC ER-, PR-, and HER2-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior PARP inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic CRC who received appropriate oxaliplatin or irinotecan- and 5-FU-based chemotherapy with or without bevacizumab.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).
Measure Participants	2	15	5	4	3
Number (95% Confidence Interval) [percentage of participants]	0.0 0%	20.0 125%	20.0 333.3%	0.0 0%	66.7 1667.5%

7. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	600 mg CB-839 + 1 mg Talazoparib	800 mg CB-839 + 1 mg Talazoparib: ccRCC	800 mg CB-839 + 1 mg Talazoparib: TNBC	800 mg CB-839 + 1 mg Talazoparib: CRC	800 mg CB-839 + 1 mg Talazoparib: Other Histology
Arm/Group Description	600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic ccRCC who received ≥ 2 prior systemic regimens including ≥ 1 VEGFR TKI therapy.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic TNBC ER-, PR-, and HER2-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior PARP inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic CRC who received appropriate oxaliplatin or irinotecan- and 5-FU-based chemotherapy with or without bevacizumab.	800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).
Measure Participants	2	15	5	4	3
Median (95% Confidence Interval) [months]	1.86	1.87	1.71	1.66	NA

Adverse Events

Time Frame	Start of treatment to 28 days post treatment; mean overall duration of talazoparib exposure was 88.7 days.
Adverse Event Reporting Description	Per protocol, the serious and nonserious adverse event tables exclude grade 5 disease progression events.
Arm/Group Title	600 mg CB-839 + 1 mg Talazoparib		800 mg CB-839 + 1 mg Talazoparib: ccRCC		800 mg CB-839 + 1 mg Talazoparib: TNBC		800 mg CB-839 + 1 mg Talazoparib: CRC		800 mg CB-839 + 1 mg Talazoparib: Other Histology
Arm/Group Description	600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.		800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic ccRCC who received ≥ 2 prior systemic regimens including ≥ 1 VEGFR TKI therapy.		800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic TNBC ER-, PR-, and HER2-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior PARP inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.		800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic CRC who received appropriate oxaliplatin or irinotecan- and 5-FU-based chemotherapy with or without bevacizumab.		800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).
All Cause Mortality
	600 mg CB-839 + 1 mg Talazoparib		800 mg CB-839 + 1 mg Talazoparib: ccRCC		800 mg CB-839 + 1 mg Talazoparib: TNBC		800 mg CB-839 + 1 mg Talazoparib: CRC		800 mg CB-839 + 1 mg Talazoparib: Other Histology
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Serious Adverse Events
	600 mg CB-839 + 1 mg Talazoparib		800 mg CB-839 + 1 mg Talazoparib: ccRCC		800 mg CB-839 + 1 mg Talazoparib: TNBC		800 mg CB-839 + 1 mg Talazoparib: CRC		800 mg CB-839 + 1 mg Talazoparib: Other Histology
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)		0/4 (0%)		3/4 (75%)
Gastrointestinal disorders
Nausea	0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Small intestinal obstruction	0/3 (0%)		0/16 (0%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Vomiting	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
General disorders
Pain	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Infections and infestations
Pyelonephritis	0/3 (0%)		0/16 (0%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Metabolism and nutrition disorders
Hypokalemia	0/3 (0%)		0/16 (0%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor associated fever	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Nervous system disorders
Muscle contractions involuntary	0/3 (0%)		0/16 (0%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	600 mg CB-839 + 1 mg Talazoparib		800 mg CB-839 + 1 mg Talazoparib: ccRCC		800 mg CB-839 + 1 mg Talazoparib: TNBC		800 mg CB-839 + 1 mg Talazoparib: CRC		800 mg CB-839 + 1 mg Talazoparib: Other Histology
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		16/16 (100%)		6/6 (100%)		3/4 (75%)		4/4 (100%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)		10/16 (62.5%)		2/6 (33.3%)		1/4 (25%)		2/4 (50%)
Thrombocytopenia	0/3 (0%)		6/16 (37.5%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Lymphopenia	0/3 (0%)		0/16 (0%)		0/6 (0%)		1/4 (25%)		0/4 (0%)
Neutropenia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Cardiac disorders
Coronary artery disease	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Eye disorders
Photophobia	1/3 (33.3%)		1/16 (6.3%)		2/6 (33.3%)		2/4 (50%)		1/4 (25%)
Gastrointestinal disorders
Nausea	1/3 (33.3%)		7/16 (43.8%)		4/6 (66.7%)		0/4 (0%)		2/4 (50%)
Vomiting	0/3 (0%)		6/16 (37.5%)		0/6 (0%)		0/4 (0%)		2/4 (50%)
Diarrhoea	1/3 (33.3%)		2/16 (12.5%)		0/6 (0%)		1/4 (25%)		1/4 (25%)
Abdominal pain	0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		1/4 (25%)		1/4 (25%)
Constipation	0/3 (0%)		3/16 (18.8%)		0/6 (0%)		1/4 (25%)		0/4 (0%)
Dyspepsia	2/3 (66.7%)		1/16 (6.3%)		0/6 (0%)		1/4 (25%)		0/4 (0%)
Stomatitis	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Abdominal distension	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Abdominal pain upper	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Dry mouth	0/3 (0%)		0/16 (0%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Dysphagia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Hypoaesthesia oral	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Lip swelling	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Oral pain	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
General disorders
Fatigue	2/3 (66.7%)		11/16 (68.8%)		3/6 (50%)		1/4 (25%)		2/4 (50%)
Pyrexia	0/3 (0%)		3/16 (18.8%)		0/6 (0%)		0/4 (0%)		2/4 (50%)
Asthenia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Chest pain	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Chills	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Face oedema	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Oedema peripheral	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Infections and infestations
Sinusitis	0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Urinary tract infection	0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Lung infection	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Otitis media acute	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Pharyngitis	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Pneumonia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Respiratory syncytial virus infection	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Injury, poisoning and procedural complications
Fall	0/3 (0%)		0/16 (0%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Investigations
Platelet count decreased	1/3 (33.3%)		4/16 (25%)		2/6 (33.3%)		0/4 (0%)		2/4 (50%)
Neutrophil count decreased	0/3 (0%)		4/16 (25%)		1/6 (16.7%)		0/4 (0%)		1/4 (25%)
White blood cell count decreased	0/3 (0%)		3/16 (18.8%)		1/6 (16.7%)		0/4 (0%)		1/4 (25%)
Blood alkaline phosphatase increased	0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)		0/4 (0%)		1/4 (25%)
Alanine aminotransferase increased	0/3 (0%)		2/16 (12.5%)		0/6 (0%)		1/4 (25%)		0/4 (0%)
Blood bilirubin increased	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Blood creatinine increased	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Weight decreased	0/3 (0%)		0/16 (0%)		2/6 (33.3%)		0/4 (0%)		0/4 (0%)
Lipase increased	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Liver function test increased	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Lymphocyte count decreased	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/3 (0%)		5/16 (31.3%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Hyponatraemia	0/3 (0%)		5/16 (31.3%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Dehydration	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		2/4 (50%)
Hypercalcaemia	0/3 (0%)		3/16 (18.8%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Hypokalaemia	0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Hypocalcaemia	0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Hyperglycaemia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Hyperlipidaemia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Hypoalbuminaemia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Hypomagnesaemia	0/3 (0%)		0/16 (0%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Musculoskeletal and connective tissue disorders
Hypophosphataemia	0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Flank pain	0/3 (0%)		4/16 (25%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Back pain	0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Arthralgia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Foot fracture	0/3 (0%)		0/16 (0%)		0/6 (0%)		1/4 (25%)		0/4 (0%)
Muscular weakness	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Musculoskeletal pain	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Pain in jaw	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Tumour pain	1/3 (33.3%)		0/16 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Nervous system disorders
Headache	0/3 (0%)		3/16 (18.8%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Dizziness	0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/4 (0%)		1/4 (25%)
Ataxia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Dysgeusia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Memory impairment	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Paraesthesia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Psychiatric disorders
Anxiety	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Insomnia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Renal and urinary disorders
Haematuria	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Reproductive system and breast disorders
Uterine mass	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)		3/16 (18.8%)		2/6 (33.3%)		0/4 (0%)		0/4 (0%)
Dyspnoea	0/3 (0%)		4/16 (25%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Asthma	0/3 (0%)		0/16 (0%)		0/6 (0%)		1/4 (25%)		0/4 (0%)
Hypoxia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Nasal congestion	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Oropharyngeal pain	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Pleural effusion	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Pleuritic pain	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Pulmonary oedema	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Blood blister	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Dry skin	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Hyperhidrosis	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Urticaria	0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/4 (0%)		0/4 (0%)
Vascular disorders
Hypotension	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		1/4 (25%)
Hypertension	0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

No publication by the PI before either a multi-site publication or 18 months after final multi-site study report. PI can only publish their own results and provide 45 days in advance notice. PI must delete any Calithera confidential information from the publication other than study results and give good faith consideration to other comments made by Calithera. The PI must delay the publication for up to 45 days if requested by Calithera and publicly acknowledge Calithera and Pfizer support.