Approval Probability
TA Base Rate
Adjusted LOA
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Also known as CB-839 Capsules, telaglenastat, Glutaminase inhibitor
CB-839 · 9 trials · 28 indications
* PFS is defined as the duration of time from start of telaglenastat to time of progression or death, whichever occurs first. * Progressive disease: New foci of abnormal FDG uptake not present on the pretreatment FDG-PET study
PFS is defined as the time from randomization to the occurrence of disease progression as assessed by the IRC using RECIST v1.1 or death from any cause, whichever occurs first. Subjects not experiencing disease progression or death at the time of analysis of PFS will be censored at the date of the last evaluable radiographic disease assessment. RECIST v1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
PFS was defined as the time from randomization to the date of documented disease progression (assessed by Investigator per Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1) within 2 scheduled scan intervals following previous evaluable radiologic tumor assessment or death for any cause, whichever occurred first. Participants with no documentation of disease progression or death on-study were censored at the date of last available tumor assessment. Progressive Disease (PD) per RECIST 1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.
ORR is defined as the percentage of patients with complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessment performed no less than 4 weeks after the criteria for response were first met.
Evaluation of the relationship between the plasma concentrations of telaglenastat and its metabolite 110826 with the ΔQTc, placebo-adjusted and corrected for HR based on the Fridericia QT correction method (ΔΔQTcF)
To assess the effect of famotidine on the Cmax of telaglenastat in healthy adult subjects
To assess the effect of famotidine on the Tmax of telaglenastat in healthy adult subjects
To assess the effect of famotidine on the time to maximum plasma concentration (Tmax) of telaglenastat in healthy adult subjects.
To assess the effect of famotidine on the AUC0-inf of telaglenastat in healthy adult subjects
To assess the effect of famotidine on the half-life of telaglenastat in healthy adult subjects
To assess the effect of famotidine on the elimination rate of telaglenastat in healthy adult subjects
| Arm | Type | Description |
|---|---|---|
| Control Arm: Standard of Care Chemoradiation | ACTIVE_COMPARATOR | -Participants will receive 7 weeks of standard of care chemoradiation. |
| Experimental Arm #1: Telaglenastat + Standard of Care Chemoradiation | EXPERIMENTAL | -Participants will receive 2 weeks of telaglenastat and 7 weeks of standard of care chemoradiation plus telaglenastat. |
| Pbo-Cabo | PLACEBO_COMPARATOR | Placebo twice daily (BID) + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first. |
| CB-Cabo | EXPERIMENTAL | CB-839 800 mg BID + cabozantinib (60 mg QD) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first. |
| CB-839 + Everolimus | ACTIVE_COMPARATOR | CB-839 is administered as oral tablets twice daily (BID) in combination with standard daily (QD) everolimus in 28 day cycles. |
| Placebo + Everolimus | PLACEBO_COMPARATOR | Placebo is administered as oral tablets BID in combination with standard QD everolimus in 28 day cycles. |
| Cohort 1 - African ancestry, 3rd line+ | EXPERIMENTAL | Intervention = Paclitaxel- CB-839 (Pac-CB) combination 1. Participants must self-identify as African ancestry (includes African American). 2. At least 2 prior lines of systemic therapy for advanced/metastatic disease including a taxane. * Prior taxane (paclitaxel, docetaxel, or nab-paclitaxel) for advanced/metastatic disease is required but must not have been received in the immediate prior line of therapy. * Systemic neoadjuvant and/or adjuvant therapy is considered a line of therapy for advanced/metastatic disease if the time to recurrence from completion of treatment was ≤ 12 mo. |
| Cohort 2 - African ancestry, 1st line | EXPERIMENTAL | Intervention = Pac-CB combination 1. Participants must self-identify as African ancestry (includes African American). 2. No prior systemic therapy for advanced or metastatic disease. * Systemic neoadjuvant or adjuvant therapy, including taxane, is allowed if time to recurrence was \> 12 mo. |
| Cohort 3 - Non-African ancestry, 3rd line+ | EXPERIMENTAL | Intervention = Pac-CB combination 1. Participants do not self-identify as African ancestry. 2. Otherwise have the same criteria as Cohort 1. |
| Cohort 4 - Non-African ancestry, 1st line | EXPERIMENTAL | Intervention = Pac-CB combination 1. Participants do not self-identify as African ancestry. 2. Otherwise have the same criteria as Cohort 2. |
| Telaglenastat | EXPERIMENTAL | 800 mg telaglenastat (4 x 200 mg tablets) administered twice daily (BID) on Days 1 3, with a single dose administered on the morning of Day 4 |
| Telaglenastat Placebo | PLACEBO_COMPARATOR | 800 mg placebo (4 x 200 mg tablets) administered twice daily (BID) on Days 1 3, with a single dose administered on the morning of Day 4 |
| Moxifloxacin | ACTIVE_COMPARATOR | Single dose of 400 mg moxifloxacin (1 x 400 mg tablet) administered on the morning of Day 4 |
| Telaglenastat and Famotidine | EXPERIMENTAL | Famotidine |
| Telaglenastat and Placebo for Famotidine | PLACEBO_COMPARATOR | Placebo for famotidine |
| CB-839 | EXPERIMENTAL | CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity |
| CB-Aza | EXPERIMENTAL | CB-839 administered as oral capsules twice daily (BID) in combination with azacitidine in 28-day cycles until disease progression or unacceptable toxicity |
| Pac-CB | EXPERIMENTAL | CB-839 administered as oral capsules twice daily (BID) in combination with standard dose paclitaxel in 28-day cycles until disease progression or unacceptable toxicity |
| CBE | EXPERIMENTAL | CB-839 administered as oral capsules twice daily (BID) in combination with standard dose everolimus in 28-day cycles until disease progression or unacceptable toxicity |
| CB-Erl | EXPERIMENTAL | CB-839 administered as oral capsules twice daily (BID) in combination with standard dose erlotnib in 28-day cycles until disease progression or unacceptable toxicity |
| CBD | EXPERIMENTAL | CB-839 administered as oral capsules twice daily (BID) in combination with standard dose docetaxel in 21-day cycles until disease progression or unacceptable toxicity |
| CB-839 and low dose dexamethasone | EXPERIMENTAL | CB-839 is administered as oral capsules twice daily with food (BIDf) in 28 day cycles in combination with dexamethasone until disease progression or unacceptable toxicity |
| CB-839, pomalidomide, and low dose dexamethasone | EXPERIMENTAL | CB-839 is administered as oral capsules twice daily with food (BIDf) in 28 day cycles in combination with pomalidomide and dexamethasone until disease progression or unacceptable toxicity |
| Name | Type | Description |
|---|---|---|
| Telaglenastat | DRUG | -800 mg twice per day by mouth |
| Radiation treatment | RADIATION | * Standard of care * External beam radiation therapy delivered daily 4 days a week and 1 day per week of brachytherapy. |
| Cisplatin | DRUG | * Standard of care * Weekly administration of cisplain |
| CB-839 | DRUG | Oral glutaminase inhibitor |
| Cabozantinib | DRUG | Oral receptor tyrosine kinase inhibitor |
| Placebo | DRUG | Placebo tablets |
| everolimus | DRUG | oral tablets |
| Paclitaxel | DRUG | standard weekly paclitaxel in 28-day cycles |
| telaglenastat placebo | OTHER | matching placebo for telaglenastat |
| moxifloxicin | OTHER | positive control |
| Famotidine | DRUG | Histamine-H2 Receptor Antagonist |
| Placebo for famotidine | DRUG | Placebo for Histamine-H2 Receptor Antagonist |
| CB-Aza | DRUG | CB-839 in combination with standard dose azacitidine |
| Pac-CB | DRUG | CB-839 in combination with standard dose paclitaxel |
| CBE | DRUG | CB-839 in combination with standard dose everolimus |
| CB-Erl | DRUG | CB-839 in combination with standard dose erlotnib |
| CBD | DRUG | CB-839 in combination with standard dose docetaxel |
| CB-Cabo | DRUG | CB-839 in combination with standard dose cabozantinib |
| CB-839 and low dose dexamethasone | DRUG | CB-839 and low dose dexamethasone |
| CB-839, pomalidomide, and low dose dexamethasone | DRUG | CB-839, pomalidomide, and low dose dexamethasone |
Inclusion Criteria: Patients eligible for definitive chemoradiotherapy, including brachytherapy * Patient age ≥ 18 years. * Patients with histologically confirmed newly diagnosed advanced cervical cancer (squamous, adenosquamous, adenocarcinoma or poorly differentiated); Federation of Gynecology a...