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

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 18 years and older
• All sexes
• No healthy volunteers
• Adult, Older adult

Trial locations and contacts

9 sites in 1 country.

About this study

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

Conditions

Solid Tumor, Clear Cell Renal Cell Carcinoma, TNBC - Triple-Negative Breast Cancer, Colorectal Cancer, CRC, RCC

Being tested

CB-839, Talazoparib

Keywords

Tumor Metabolism, Glutaminase Inhibitor, CB-839, telaglenastat, talazoparib, PARP Inhibitor, DNA Damage, DNA Repair, Homologous recombination deficiency, HRD, BRCA 1, BRCA 2

Medical subject headings

Carcinoma, Renal Cell, Triple Negative Breast Neoplasms, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• CB-839Drug

  Also called telaglenastat

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

• TalazoparibDrug

  Also called Talzenna

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

What is being measured

The primary outcome is the main question the study is designed to answer.

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

   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.

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

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

   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.

   Measured: 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.

3. Number of Participants With Dose-Limiting Toxicities (DLTs)

   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.

   Measured: During Cycle 1 on Days 1 through 28, inclusive

4. Overall Response Rate (ORR)

   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).

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

5. Confirmed ORR (cORR)

   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).

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

6. Clinical Benefit Rate (CBR)

   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).

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

7. Progression-Free Survival (PFS)

   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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted14 Mar 2019
2. Study start20 May 2019
3. Primary completion29 Jul 2020
4. Study completion29 Jul 2020

Why it stopped: Slow Enrollment

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Other trials for Solid TumorStudies of the same condition, open and under way.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.