Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Breast Neoplasms

Carcinoma

Triple Negative Breast Neoplasms

Carcinoma, Renal Cell

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Breast Diseases

Skin Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Gastrointestinal Agents

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Amino Acids

Irinotecan

Bevacizumab

Fluorouracil

Estrogens

Oxaliplatin

Endothelial Growth Factors

Mitogens

Tyrosine Kinase Inhibitors

Pancrelipase

Progesterone

Adenosine

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Pancreatin

Enzyme Inhibitors

Tyrosine

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)-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.

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).

CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.

CB-839

Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.

Sam Whiting, MD, PhD

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.

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

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

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.

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.

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.

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).

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).

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).

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.

Calithera Biosciences, Inc

Per protocol, the serious and nonserious adverse event tables exclude grade 5 disease progression events.

600 mg CB-839 + 1 mg Talazoparib

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 + 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 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 + 1 mg Talazoparib: 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 + 1 mg Talazoparib: CRC

800 mg CB-839 + 1 mg Talazoparib: Other Histology

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Asian

Black or African American

White

Other, Not Specified

Not Reported

Race/Ethnicity, Customized

Study Director

AE grade ≥ 3

AE related to telaglenastat

AE related to talazoparib

AE related to telaglenastat and talazoparib

AE grade ≥ 3 related to telaglenastat

AE grade ≥ 3 related to talazoparib

AE leading to discontinuation of telaglenastat

AE leading to discontinuation of talazoparib

AE leading to discontinuation of telaglenastat and talazoparib

AE leading to discontinuation of telaglenastat or talazoparib

AE leading to telaglenastat dose interruption or reduction

AE leading to talazoparib dose interruption or reduction

AE leading to telaglenastat and talazoparib dose interruption or reduction

AE leading to telaglenastat or talazoparib dose interruption or reduction

SAE with CTCAE grade 5

SAE with CTCAE grade 5 related to telaglenastat

SAE with CTCAE grade 5 related to talazoparib

SAE grade ≥ 3

SAE related to telaglenastat

SAE related to talazoparib

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

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

Hematology

Clinical Chemistry

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

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.

Number of Participants With Dose-Limiting Toxicities (DLTs)

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 (ORR)

Confirmed ORR (cORR)

Clinical Benefit Rate (CBR)

Progression-Free Survival (PFS)

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.

Overall Study

Spots Global Cancer Trial Database for Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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