A Phase 1/2 interventional study of CGT9486 and Pexidartinib in Gastrointestinal Stromal Tumors, sponsored by Cogent Biosciences, Inc.. Completed at 6 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-02-14.
Sponsored by Cogent Biosciences, Inc. · Phase 1/2, Interventional, and Treatment
The goal of this clinical research study is to learn how CGT9486 (fka PLX9486) may affect cancer cells with certain mutations in the KIT gene, specifically in participants with types of advanced solid tumors including gastrointestinal stromal tumor (GIST).
CGT9486 (fka PLX9486) is designed to block KIT gene mutations. These mutations can cause cancer and cancer cell growth. By blocking these mutations, the drug may kill the cancer cells with the mutation and/or stop the tumor from growing. By combining CGT9486 (fka PLX9486) with PLX3397 and CGT9486 (fka PLX9486) with sunitinib, the investigators hope to block most KIT gene mutations that drive cancer growth.
This study includes a dose escalation portion (Part 1) in which the safety profile and recommended phase 2 dose (RP2D) of CGT9486 as a single oral agent will be evaluated in participants with solid tumors (including GIST), followed by signal-seeking extension cohorts (Part 2). Enrollment in the combination treatment portions of the study (dose-finding for the CGT9486 + pexidartinib combination [Part 2b] and the CGT9486 + sunitinib combination [Part 2e]) is planned to be accrued using standard 3+3 study designs.
Parts 2a, 2c, 2d, and 2f are not conducted due to business decisions.
345 studies on the registry are indexed under Gastrointestinal Stromal Tumors; 60 are open to participants now.
This study's enrollment of 51 is close to the median of 50 across 253 interventional studies indexed under Gastrointestinal Stromal Tumors.
Browse Gastrointestinal Stromal Tumors studies →Cogent Biosciences, Inc. is the lead sponsor of 14 studies on the registry; 6 are open to participants now.
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Exclusion Criteria:
Participants will receive CGT9486 250 milligrams (mg) orally once daily (QD) in 28-day dosing cycles. Treatment will continue until participant discontinuation, withdrawal, or study termination.
Drug: CGT9486
Participants will receive CGT9486 350 mg orally QD in 28-day dosing cycles. Treatment will continue until participant discontinuation, withdrawal, or study termination.
Drug: CGT9486
Participants will receive CGT9486 500 mg orally QD in 28-day dosing cycles. Treatment will continue until participant discontinuation, withdrawal, or study termination.
Drug: CGT9486
Participants will receive CGT9486 1000 mg orally QD in 28-day dosing cycles. Treatment will continue until participant discontinuation, withdrawal, or study termination.
Drug: CGT9486
Participants will receive CGT9486 500 mg orally twice daily (BID) in 28-day dosing cycles. Treatment will continue until participant discontinuation, withdrawal, or study termination.
Drug: CGT9486
Participants in fasting condition will receive CGT9486 500 mg orally QD in combination with pexidartinib 600 mg (administered as 1 capsule of 200 mg in the morning and 2 capsules of 200 mg in the evening) orally in 28-day dosing cycles. Treatment will continue until participant discontinuation, withdrawal, or study termination.
Drug: CGT9486 · Drug: Pexidartinib
Participants in non-fasting condition will receive CGT9486 500 mg orally QD in combination with pexidartinib 600 mg (administered as 1 capsule of 200 mg in the morning and 2 capsules of 200 mg in the evening) orally in 28-day dosing cycles. Treatment will continue until participant discontinuation, withdrawal, or study termination.
Drug: CGT9486 · Drug: Pexidartinib
Participants will receive CGT9486 500 mg orally QD in combination with sunitinib 25 mg orally in 28-day dosing cycles. Treatment will continue until participant discontinuation, withdrawal, or study termination.
Drug: CGT9486 · Drug: Sunitinib
Participants will receive CGT9486 1000 mg orally QD in combination with sunitinib 25 mg orally in 28-day dosing cycles. Treatment will continue until participant discontinuation, withdrawal, or study termination.
Drug: CGT9486 · Drug: Sunitinib
Participants will receive CGT9486 1000 mg orally QD in combination with sunitinib 37.5 mg orally in 28-day dosing cycles. Treatment will continue until participant discontinuation, withdrawal, or study termination.
Drug: CGT9486 · Drug: Sunitinib
CGT9486 will be administered per dose and schedule specified in the arm.
Pexidartinib capsules will be administered per dose and schedule specified in the arm.
Also known as: PLX3397
Sunitinib will be administered per dose and schedule specified in the arm.
Part 1: Recommended Phase 2 Dose (RP2D) of CGT9486
RP2D was determined by incidence of dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) V4.03. DLTs: AEs that occurred during Cycle 1, possibly/probably related to study drug, and met 1 of the following criteria: Hematologic Toxicities: Grade 4 neutropenia for \>7 days, Grade ≥3 neutropenia with fever, Grade 4 thrombocytopenia, Grade ≥3 thrombocytopenia for \>7 days, Grade 4 anemia; Other Toxicities: Any Grade ≥3 (AE or laboratory) toxicity despite adequate supportive care except for following: Grade ≥3 nausea, vomiting, or diarrhea that resolved to Grade ≤2 within 72 hours; Grade 3 fatigue that resolved to Grade ≤2 within 14 days; Grade ≥3 asymptomatic changes in alkaline phosphatase, hypomagnesemia, hyperglycemia, or hypophosphatemia; Grade 3 increases in transaminases for ≤5 days; Any other Grade ≥3 toxicity for which further dose escalation deemed inappropriate.
Time frame: Cycle 1 of Part 1 (Cycle length = 28 days)
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant administered study drug, which did not necessarily have a causal relationship with the treatment. An AE could be any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not it was considered to be study drug related. This included any newly occurring event or previous condition that had increased in severity or frequency since the administration of study drug. A treatment-emergent AE (TEAE) was an AE that started or worsened in severity on or after the date of the initial dose of study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: From the date of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 670 days)
Part 1: Area Under The Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC0-24) of CGT9486
AUC0-24 was determined by the linear trapezoidal rule for the ascending portion and by the log trapezoidal rule for the descending portion of the plasma profile. For BID dosing, Cycle 1 Day 15 AUC0-24 was calculated as 2 x area under the concentration time curve from time zero to 12 hours after dosing (AUC0-12). Missing concentration data were excluded from Pharmacokinetic (PK) analysis.
Time frame: Predose, 1, 3, 5, 7, 9, and 24 hours postdose at Cycle 1 Day 1 and Cycle 1 Day 15
Part 1: Maximum Observed Plasma Concentration (Cmax) of CGT9486
Cmax was taken directly from bioanalytical data.
Time frame: Predose, 1, 3, 5, 7, 9, and 24 hours postdose at Cycle 1 Day 1 and Cycle 1 Day 15
Part 1: Time to Reach Cmax (Tmax) of CGT9486
Tmax was taken directly from merged clinical and bioanalytical data, with time presented as nominal time relative to dose.
Time frame: Predose, 1, 3, 5, 7, 9, and 24 hours postdose at Cycle 1 Day 1 (Day -10 for 350 mg QD cohort) and Cycle 1 Day 15
Part 1: Half Life (T1/2) of PLX9486
Participants in a selected Part 1 cohort (350 mg QD) participated in a PK substudy to obtain more complete information on the PK profile of PLX9486. Participants received a single dose of 350 mg of PLX9486 10 days prior to the start of repeated QD dosing and plasma concentrations were followed 0.5, 1, 2, 4, 6, and 9 hours postdose, and then once daily for 9 additional days prior to Cycle 1 Day 1.
Time frame: Predose, 0.5, 1, 2, 4, 9, 24, 49, 72, 96, 120, 144, 168, 192, 216 hours postdose on Day -10
Part 2e: RP2D of CGT9486 in Combination With Sunitinib
RP2D was determined by incidence of DLT using CTCAE version 4.03 for severity grade. DLTs were defined as AEs that occurred during Cycle 1, classified as possibly/probably related to study drug, and met 1 of the following criteria: Hematologic Toxicities: Grade 4 neutropenia for \>7 days, Grade ≥3 neutropenia with fever, Grade 4 thrombocytopenia, Grade ≥3 thrombocytopenia for \>7 days or with bleeding, Grade 4 anemia; Other Toxicities: Any Grade ≥3 (AE or laboratory) toxicity despite adequate supportive care except for the following: Grade ≥3 nausea, vomiting, or diarrhea that resolved to Grade ≤2 within 72 hours; Grade 3 fatigue that resolved to Grade ≤2 within 14 days; Grade ≥3 asymptomatic changes in alkaline phosphatase, hypomagnesemia, hyperglycemia, or hypophosphatemia; Grade 3 increases in transaminases for ≤5 days; Any other Grade ≥3 toxicity for which further dose escalation deemed inappropriate.
Time frame: Cycle 1 of Part 2e (Cycle length = 28 days)
Part 2b: RP2D of PLX9486 in Combination With Pexidartinib
RP2D was determined by incidence of DLT using CTCAE version 4.03 for severity grade. DLTs were defined as AEs that occurred during Cycle 1, classified as possibly/probably related to study drug, and met 1 of the following criteria: Hematologic Toxicities: Grade 4 neutropenia for \>7 days, Grade ≥3 neutropenia with fever, Grade 4 thrombocytopenia, Grade ≥3 thrombocytopenia for \>7 days or with bleeding, Grade 4 anemia; Other Toxicities: Any Grade ≥3 (AE or laboratory) toxicity despite adequate supportive care except for the following: Grade ≥3 nausea, vomiting, or diarrhea that resolved to Grade ≤2 within 72 hours; Grade 3 fatigue that resolved to Grade ≤2 within 14 days; Grade ≥3 asymptomatic changes in alkaline phosphatase, hypomagnesemia, hyperglycemia, or hypophosphatemia; Grade 3 increases in transaminases for ≤5 days; Any other Grade ≥3 toxicity for which further dose escalation deemed inappropriate.
Time frame: Cycle 1 of Part 2 b (Cycle length = 28 days)
Part 2b: Number of Participants With Any TEAEs and Treatment-Related TEAEs
An AE was any untoward medical occurrence in a participant administered study drug, which did not necessarily have a causal relationship with the treatment. An AE could be any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not it was considered to be study drug related. This included any newly occurring event or previous condition that had increased in severity or frequency since the administration of study drug. A TEAE was an AE that started or worsened in severity on or after the date of the initial dose of study drug. Treatment-related TEAEs included all events reported as "possibly related" or "probably related" to any of study treatment. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: From the date of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 868 days)
Part 2e: Number of Participants With Any TEAEs and Treatment-Related TEAEs
An AE was any untoward medical occurrence in a participant administered study drug, which did not necessarily have a causal relationship with the treatment. An AE could be any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not it was considered to be study drug related. This included any newly occurring event or previous condition that had increased in severity or frequency since the administration of study drug. A TEAE was an AE that started or worsened in severity on or after the date of the initial dose of study drug. Treatment-related TEAEs included all events reported as "possibly related" or "probably related" to any of study treatment. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: From the date of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 825 days)
Part 1: Overall Response Rate (ORR): Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR), as Assessed Using RECIST V1.1
ORR was defined as the percentage of participants who achieved a best overall response of confirmed complete response (CR) or partial response (PR). CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From the date of first dose of study drug until the first appearance of CR or PR (maximum exposure: 670 days)
Part 1: Progression-Free Survival (PFS), as Assessed Using RECIST V1.1
PFS was defined as the number of days from the first day of treatment (Cycle 1 Day 1) to the date of the first documented disease progression or date of death, whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. Median was calculated using Kaplan-Meier estimate.
Time frame: From the first date of treatment until the first documented disease progression or date of death (maximum exposure: 670 days)
Part 1: Duration of Response (DOR), as Assessed Using RECIST V1.1
DOR was defined as the number of days from the date of first response (PR or CR confirmed at least 28 days later) to the date of first documented disease progression/relapse or death, whichever occurred first. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (target or non-target) must had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. Median was calculated using Kaplan-Meier estimate.
Time frame: From the date of first response (PR or CR) to the date of first documented disease progression/relapse or death, whichever occurred first (maximum exposure: 670 days)
Part 2: Overall Response Rate (ORR): Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR), as Assessed Using RECIST V1.1
ORR was defined as the percentage of participants who achieved a best overall response of confirmed CR or PR. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From the date of first dose of study drug until the first appearance of CR or PR (maximum exposure: 868 days)
Part 2: Clinical Benefit Rate (CBR): Percentage of Participants With Clinical Benefit, as Assessed Using RECIST V1.1
Participants were considered to experience clinical benefit if they had a best overall response of stable disease (SD) that lasted for at least 16 weeks, or confirmed best overall response of PR or CR. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters. CR: Disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (target or non-target) must had 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. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression.
Time frame: From the date of first dose of study drug until the first appearance of CR, PR, or SD (maximum exposure: 868 days)
Part 2: Progression-Free Survival (PFS), as Assessed Using RECIST V1.1
PFS was defined as the number of days from the first day of treatment (Cycle 1 Day 1) to the date of the first documented disease progression or date of death, whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. Median was calculated using Kaplan-Meier estimate.
Time frame: From the first date of treatment until the first documented disease progression or date of death (maximum exposure: 868 days)
Part 2: Overall Survival
Overall Survival was defined as the number of days from the first day of treatment (Cycle 1 Day 1) until the date of death. If a participant was lost to follow-up, overall survival was censored at the date of last contact. Median was calculated using Kaplan-Meier estimate.
Time frame: From the first day of treatment until the date of death (maximum exposure: 868 days)
Part 2: Overall Survival at Month 12
Percentage of participants who survived at Month 12 have been reported.
Time frame: Month 12
Part 2: PFS at Month 6
PFS was defined as the number of days from the first day of treatment (Cycle 1 Day 1) to the date of the first documented disease progression or date of death, whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. Percentage of participants with PFS at Month 6 are reported.
Time frame: Month 6
Part 2: Duration of Response (DOR), as Assessed Using RECIST V1.1
DOR was defined as the number of days from the date of first response (PR or CR confirmed at least 28 days later) to the date of first documented disease progression/relapse or death, whichever occurred first. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (target or non-target) must had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. Median was calculated using Kaplan-Meier estimate.
Time frame: From the date of first response (PR or CR) to the date of first documented disease progression/relapse or death, whichever occurred first (maximum exposure: 868 days)
Part 2: AUC0-24 of CGT9486 in Combination With Pexidartinib or Sunitinib
AUC0-24 was determined by the linear trapezoidal rule for the ascending portion and by the log trapezoidal rule for the descending portion of the plasma profile. Missing concentration data were excluded from PK analysis.
Time frame: Predose, 1, 3, 5, 7, 9, and 24 hours postdose at Cycle 1 Day 1 and Cycle 1 Day 15
Part 2: Cmax of CGT9486 in Combination With Pexidartinib or Sunitinib
Cmax was taken directly from bioanalytical data.
Time frame: Predose, 1, 3, 5, 7, 9, and 24 hours postdose at Cycle 1 Day 1 and Cycle 1 Day 15
Part 2: Tmax of CGT9486 in Combination With Pexidartinib or Sunitinib
Tmax was taken directly from merged clinical and bioanalytical data, with time presented as nominal time relative to dose.
Time frame: Predose, 1, 3, 5, 7, 9, and 24 hours postdose at Cycle 1 Day 1 and Cycle 1 Day 15
This study included a dose escalation portion (Part 1) in which the safety profile and recommended phase 2 dose (RP2D) of CGT9486 as a single oral agent was evaluated in participants with solid tumors (including gastrointestinal stromal tumor \[GIST\]), followed by signal-seeking extension cohorts of CGT9486 in combination with pexidartinib or sunitinib (Part 2). Parts 2a, 2c, 2d, and 2f were not conducted due to business decisions.
| Milestone | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1: CGT9486 500 mg BID | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Started | 3 | 4 | 3 | 7 | 7 | 0 | 0 | 0 | 0 | 0 |
| Received at least 1 dose of study drug | 3 | 4 | 3 | 7 | 7 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 3 | 4 | 3 | 7 | 7 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Clinical progression | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Death | 1 | 2 | 3 | 5 | 4 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Progressive disease (per recist) | 0 | 2 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1: CGT9486 500 mg BID | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 4 | 8 | 0 | 0 | 0 |
| Received at least 1 dose of study drug | 0 | 0 | 0 | 0 | 0 | 4 | 8 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 4 | 8 | 0 | 0 | 0 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Withdrew: Progressive disease (per recist) | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0 | 0 |
| Withdrew: Other than specified | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Milestone | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1: CGT9486 500 mg BID | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 5 | 10 |
| Received at least 1 dose of study drug | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 5 | 10 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 5 | 10 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 4 |
| Withdrew: Progressive disease (per recist) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Withdrew: Clinical progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Withdrew: Other than specified | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 3 |
RP2D was determined by incidence of dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) V4.03. DLTs: AEs that occurred during Cycle 1, possibly/probably related to study drug, and met 1 of the following criteria: Hematologic Toxicities: Grade 4 neutropenia for \>7 days, Grade ≥3 neutropenia with fever, Grade 4 thrombocytopenia, Grade ≥3 thrombocytopenia for \>7 days, Grade 4 anemia; Other Toxicities: Any Grade ≥3 (AE or laboratory) toxicity despite adequate supportive care except for following: Grade ≥3 nausea, vomiting, or diarrhea that resolved to Grade ≤2 within 72 hours; Grade 3 fatigue that resolved to Grade ≤2 within 14 days; Grade ≥3 asymptomatic changes in alkaline phosphatase, hypomagnesemia, hyperglycemia, or hypophosphatemia; Grade 3 increases in transaminases for ≤5 days; Any other Grade ≥3 toxicity for which further dose escalation deemed inappropriate.
| mg | Part 1: CGT9486 (Single-Agent) |
|---|---|
| Part 1: Recommended Phase 2 Dose (RP2D) of CGT9486 | 1000 |
An adverse event (AE) was any untoward medical occurrence in a participant administered study drug, which did not necessarily have a causal relationship with the treatment. An AE could be any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not it was considered to be study drug related. This included any newly occurring event or previous condition that had increased in severity or frequency since the administration of study drug. A treatment-emergent AE (TEAE) was an AE that started or worsened in severity on or after the date of the initial dose of study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
| Participants | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1: CGT9486 500 mg BID |
|---|---|---|---|---|---|
| Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 | 4 | 3 | 7 | 7 |
AUC0-24 was determined by the linear trapezoidal rule for the ascending portion and by the log trapezoidal rule for the descending portion of the plasma profile. For BID dosing, Cycle 1 Day 15 AUC0-24 was calculated as 2 x area under the concentration time curve from time zero to 12 hours after dosing (AUC0-12). Missing concentration data were excluded from Pharmacokinetic (PK) analysis.
| nanograms (ng)*hour/milliliter (mL) | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1: CGT9486 500 mg BID |
|---|---|---|---|---|---|
| Cycle 1, Day 1 | 9240 ± 8.7 | 7200 ± 20.7 | 5980 ± 41.7 | 11000 ± 26.3 | NA ± NA |
| Cycle 1, Day 15 | 18500 ± 43.7 | 21300 ± 27.7 | 15400 ± 65.8 | 22100 ± 56 | 24800 ± 51.4 |
Cmax was taken directly from bioanalytical data.
| ng/mL | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1: CGT9486 500 mg BID |
|---|---|---|---|---|---|
| Cycle 1, Day 1 | 499 ± 6.92 | 332 ± 17.9 | 382 ± 6.48 | 558 ± 28.1 | 331 ± 22.8 |
| Cycle 1, Day 15 | 869 ± 38.4 | 1010 ± 27.5 | 714 ± 64.9 | 1060 ± 59 | 1150 ± 52.4 |
Tmax was taken directly from merged clinical and bioanalytical data, with time presented as nominal time relative to dose.
| hours | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1:CGT9486 500 mg BID |
|---|---|---|---|---|---|
| Cycle 1, Day 1 (or Day -10) | 9 (9 to 24) | 16.5 (9 to 24) | 15 (6 to 24) | 9 (3 to 24) | 7 (3 to 9) |
| Cycle 1, Day 15 | 3 (1 to 24) | 9 (0 to 9) | 7 (7 to 24) | 6 (3 to 24) | 5 (1 to 9) |
Participants in a selected Part 1 cohort (350 mg QD) participated in a PK substudy to obtain more complete information on the PK profile of PLX9486. Participants received a single dose of 350 mg of PLX9486 10 days prior to the start of repeated QD dosing and plasma concentrations were followed 0.5, 1, 2, 4, 6, and 9 hours postdose, and then once daily for 9 additional days prior to Cycle 1 Day 1.
| hours | Part 1: CGT9486 350 mg |
|---|---|
| Part 1: Half Life (T1/2) of PLX9486 | 75.4 ± 26.1 |
RP2D was determined by incidence of DLT using CTCAE version 4.03 for severity grade. DLTs were defined as AEs that occurred during Cycle 1, classified as possibly/probably related to study drug, and met 1 of the following criteria: Hematologic Toxicities: Grade 4 neutropenia for \>7 days, Grade ≥3 neutropenia with fever, Grade 4 thrombocytopenia, Grade ≥3 thrombocytopenia for \>7 days or with bleeding, Grade 4 anemia; Other Toxicities: Any Grade ≥3 (AE or laboratory) toxicity despite adequate supportive care except for the following: Grade ≥3 nausea, vomiting, or diarrhea that resolved to Grade ≤2 within 72 hours; Grade 3 fatigue that resolved to Grade ≤2 within 14 days; Grade ≥3 asymptomatic changes in alkaline phosphatase, hypomagnesemia, hyperglycemia, or hypophosphatemia; Grade 3 increases in transaminases for ≤5 days; Any other Grade ≥3 toxicity for which further dose escalation deemed inappropriate.
| mg | Part 2e: CGT9486 + Sunitinib |
|---|---|
| Part 2e: RP2D of CGT9486 in Combination With Sunitinib | 1000 |
RP2D was determined by incidence of DLT using CTCAE version 4.03 for severity grade. DLTs were defined as AEs that occurred during Cycle 1, classified as possibly/probably related to study drug, and met 1 of the following criteria: Hematologic Toxicities: Grade 4 neutropenia for \>7 days, Grade ≥3 neutropenia with fever, Grade 4 thrombocytopenia, Grade ≥3 thrombocytopenia for \>7 days or with bleeding, Grade 4 anemia; Other Toxicities: Any Grade ≥3 (AE or laboratory) toxicity despite adequate supportive care except for the following: Grade ≥3 nausea, vomiting, or diarrhea that resolved to Grade ≤2 within 72 hours; Grade 3 fatigue that resolved to Grade ≤2 within 14 days; Grade ≥3 asymptomatic changes in alkaline phosphatase, hypomagnesemia, hyperglycemia, or hypophosphatemia; Grade 3 increases in transaminases for ≤5 days; Any other Grade ≥3 toxicity for which further dose escalation deemed inappropriate.
| mg | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) |
|---|---|---|
| Part 2b: RP2D of PLX9486 in Combination With Pexidartinib | NA | NA |
An AE was any untoward medical occurrence in a participant administered study drug, which did not necessarily have a causal relationship with the treatment. An AE could be any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not it was considered to be study drug related. This included any newly occurring event or previous condition that had increased in severity or frequency since the administration of study drug. A TEAE was an AE that started or worsened in severity on or after the date of the initial dose of study drug. Treatment-related TEAEs included all events reported as "possibly related" or "probably related" to any of study treatment. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
| Participants | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) |
|---|---|---|
| TEAEs | 4 | 8 |
| Related TEAEs | 4 | 7 |
An AE was any untoward medical occurrence in a participant administered study drug, which did not necessarily have a causal relationship with the treatment. An AE could be any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not it was considered to be study drug related. This included any newly occurring event or previous condition that had increased in severity or frequency since the administration of study drug. A TEAE was an AE that started or worsened in severity on or after the date of the initial dose of study drug. Treatment-related TEAEs included all events reported as "possibly related" or "probably related" to any of study treatment. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
| Participants | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|
| TEAEs | 3 | 5 | 10 |
| Related TEAEs | 3 | 5 | 9 |
ORR was defined as the percentage of participants who achieved a best overall response of confirmed complete response (CR) or partial response (PR). CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
| percentage of participants | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1: CGT9486 500 mg BID |
|---|---|---|---|---|---|
| Part 1: Overall Response Rate (ORR): Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR), as Assessed Using RECIST V1.1 | 0 (0.0 to 70.8) | 0 (0.0 to 60.2) | 0 (0.0 to 70.8) | 14.3 (0.4 to 57.9) | 0 (0.0 to 45.9) |
PFS was defined as the number of days from the first day of treatment (Cycle 1 Day 1) to the date of the first documented disease progression or date of death, whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. Median was calculated using Kaplan-Meier estimate.
| days | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1: CGT9486 500 mg BID |
|---|---|---|---|---|---|
| Part 1: Progression-Free Survival (PFS), as Assessed Using RECIST V1.1 | 54 (28 to 56) | 53 (20 to 53) | 48 (47 to 221) | 144 (38 to 335) | 186 (20 to 669) |
DOR was defined as the number of days from the date of first response (PR or CR confirmed at least 28 days later) to the date of first documented disease progression/relapse or death, whichever occurred first. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (target or non-target) must had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. Median was calculated using Kaplan-Meier estimate.
| days | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1: CGT9486 500 mg BID |
|---|---|---|---|---|---|
| Part 1: Duration of Response (DOR), as Assessed Using RECIST V1.1 | — | — | — | 224 | — |
ORR was defined as the percentage of participants who achieved a best overall response of confirmed CR or PR. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
| percentage of participants | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|
| Part 2: Overall Response Rate (ORR): Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR), as Assessed Using RECIST V1.1 | 33.3 (0.8 to 90.6) | 0 (0.0 to 36.9) | 33.3 (0.8 to 90.6) | 0 (0.0 to 52.2) | 28.6 (3.7 to 71.0) |
Participants were considered to experience clinical benefit if they had a best overall response of stable disease (SD) that lasted for at least 16 weeks, or confirmed best overall response of PR or CR. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters. CR: Disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (target or non-target) must had 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. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression.
| percentage of participants | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|
| Part 2: Clinical Benefit Rate (CBR): Percentage of Participants With Clinical Benefit, as Assessed Using RECIST V1.1 | 100 (29.2 to 100) | 37.5 (8.5 to 75.5) | 100 (29.2 to 100) | 60.0 (14.7 to 94.7) | 85.7 (42.1 to 99.6) |
PFS was defined as the number of days from the first day of treatment (Cycle 1 Day 1) to the date of the first documented disease progression or date of death, whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. Median was calculated using Kaplan-Meier estimate.
| days | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|
| Part 2: Progression-Free Survival (PFS), as Assessed Using RECIST V1.1 | 333 (234 to 336) | 128 (26 to 867) | NA (503 to NA) | 319 (26 to 530) | NA (41 to NA) |
Overall Survival was defined as the number of days from the first day of treatment (Cycle 1 Day 1) until the date of death. If a participant was lost to follow-up, overall survival was censored at the date of last contact. Median was calculated using Kaplan-Meier estimate.
| days | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e:CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|
| Part 2: Overall Survival | 853 (240 to 853) | 414 (106 to NA) | NA (551 to NA) | 362 (164 to NA) | NA (98 to NA) |
Percentage of participants who survived at Month 12 have been reported.
| percentage of participants | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|
| Part 2: Overall Survival at Month 12 | 66.7 (5.4 to 94.5) | 55.6 (7.3 to 87.6) | 100 (100 to 100) | 40.0 (5.2 to 75.3) | 68.6 (21.3 to 91.2) |
PFS was defined as the number of days from the first day of treatment (Cycle 1 Day 1) to the date of the first documented disease progression or date of death, whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. Percentage of participants with PFS at Month 6 are reported.
| percentage of participants | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|
| Part 2: PFS at Month 6 | 100 (100 to 100) | 25.0 (1.4 to 63.5) | 100 (100 to 100) | 60.0 (12.6 to 88.2) | 85.7 (33.4 to 97.9) |
DOR was defined as the number of days from the date of first response (PR or CR confirmed at least 28 days later) to the date of first documented disease progression/relapse or death, whichever occurred first. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (target or non-target) must had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. Median was calculated using Kaplan-Meier estimate.
| days | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|
| Part 2: Duration of Response (DOR), as Assessed Using RECIST V1.1 | 169 | — | NA (NA to NA) | — | NA (NA to NA) |
AUC0-24 was determined by the linear trapezoidal rule for the ascending portion and by the log trapezoidal rule for the descending portion of the plasma profile. Missing concentration data were excluded from PK analysis.
| ng*hour/mL | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|
| Cycle 1, Day 1 | 7810 ± 31.6 | 7910 ± 21.9 | 9800 ± 69.4 | 14800 ± 16.3 | 12700 ± 28.5 |
| Cycle 1, Day 15 | 20300 ± 53.2 | 19100 ± 32.5 | 26500 ± 61.3 | 41400 ± 28.9 | 38300 ± 43.3 |
Cmax was taken directly from bioanalytical data.
| ng/mL | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|
| Cycle 1, Day 1 | 384 ± 34.4 | 412 ± 26.8 | 512 ± 69.2 | 866 ± 10.9 | 681 ± 28.1 |
| Cycle 1, Day 15 | 991 ± 53.9 | 924 ± 30.7 | 1200 ± 61 | 2040 ± 13.7 | 1850 ± 42.5 |
Tmax was taken directly from merged clinical and bioanalytical data, with time presented as nominal time relative to dose.
| hours | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|
| Cycle 1, Day 1 | 8 (3 to 24) | 9 (5 to 24) | 9 (7 to 9) | 24 (7 to 24) | 9 (7 to 24) |
| Cycle 2, Day 15 | 5 (5 to 9) | 6 (3 to 9) | 3 (0 to 9) | 9 (3 to 24) | 3 (0 to 24) |
Collected over From the date of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 670 days for Part 1; 868 days for Part 2b; 825 days for Part 2e). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1: CGT9486 250 mg QD | 1/3 (33.3%) | 0/3 (0%) | 3/3 (100%) |
| Part 1: CGT9486 350 mg QD | 3/4 (75%) | 2/4 (50%) | 4/4 (100%) |
| Part 1: CGT9486 500 mg QD | 3/3 (100%) | 1/3 (33.3%) | 3/3 (100%) |
| Part 1: CGT9486 1000 mg QD | 5/7 (71.4%) | 1/7 (14.3%) | 7/7 (100%) |
| Part 1: CGT9486 500 mg BID | 4/7 (57.1%) | 3/7 (42.9%) | 7/7 (100%) |
| Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | 2/4 (50%) | 2/4 (50%) | 4/4 (100%) |
| Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | 0/8 (0%) | 0/8 (0%) | 8/8 (100%) |
| Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | 1/3 (33.3%) | 1/3 (33.3%) | 3/3 (100%) |
| Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | 1/5 (20%) | 1/5 (20%) | 5/5 (100%) |
| Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg | 4/10 (40%) | 4/10 (40%) | 10/10 (100%) |
| Event | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1: CGT9486 500 mg BID | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Procedural vomitingInjury, poisoning and procedural complications | 0/3 | 0/4 | 1/3 | 0/7 | 0/7 | 0/4 | 0/8 | 0/3 | 0/5 | 0/10 |
| Prophylaxis against dehydrationSurgical and medical procedures | 0/3 | 0/4 | 1/3 | 0/7 | 0/7 | 0/4 | 0/8 | 0/3 | 0/5 | 0/10 |
| AnaemiaBlood and lymphatic system disorders | 0/3 | 0/4 | 0/3 | 0/7 | 1/7 | 1/4 | 0/8 | 1/3 | 0/5 | 0/10 |
| Small intestinal obstructionGastrointestinal disorders | 0/3 | 1/4 | 0/3 | 0/7 | 0/7 | 1/4 | 0/8 | 0/3 | 1/5 | 0/10 |
| Haemorrhoidal haemorrhageGastrointestinal disorders | 0/3 | 1/4 | 0/3 | 0/7 | 0/7 | 0/4 | 0/8 | 0/3 | 0/5 | 0/10 |
| Gastrointestinal haemorrhageGastrointestinal disorders | 0/3 | 1/4 | 0/3 | 0/7 | 0/7 | 0/4 | 0/8 | 0/3 | 0/5 | 1/10 |
| AsthmaRespiratory, thoracic and mediastinal disorders | 0/3 | 0/4 | 0/3 | 0/7 | 0/7 | 1/4 | 0/8 | 0/3 | 0/5 | 0/10 |
| MelaenaGastrointestinal disorders | 0/3 | 0/4 | 0/3 | 0/7 | 0/7 | 1/4 | 0/8 | 0/3 | 0/5 | 0/10 |
| Abdominal abscessInfections and infestations | 0/3 | 0/4 | 0/3 | 0/7 | 0/7 | 0/4 | 0/8 | 0/3 | 1/5 | 0/10 |
| HyperuricaemiaMetabolism and nutrition disorders | 0/3 | 0/4 | 0/3 | 1/7 | 0/7 | 0/4 | 0/8 | 0/3 | 0/5 | 0/10 |
| Event | Part 1: CGT9486 250 mg QD | Part 1: CGT9486 350 mg QD | Part 1: CGT9486 500 mg QD | Part 1: CGT9486 1000 mg QD | Part 1: CGT9486 500 mg BID | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Fasting) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg (Non-Fasting) | Part 2e: CGT9486 500 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 25 mg | Part 2e: CGT9486 1000 mg QD + Sunitinib 37.5 mg |
|---|---|---|---|---|---|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 2/3 | 1/4 | 1/3 | 2/7 | 4/7 | 1/4 | 3/8 | 3/3 | 2/5 | 8/10 |
| NauseaGastrointestinal disorders | 2/3 | 1/4 | 2/3 | 3/7 | 1/7 | 0/4 | 3/8 | 3/3 | 2/5 | 5/10 |
| Decreased appetiteMetabolism and nutrition disorders | 0/3 | 1/4 | 0/3 | 2/7 | 2/7 | 2/4 | 2/8 | 3/3 | 2/5 | 2/10 |
| FatigueGeneral disorders | 0/3 | 4/4 | 0/3 | 4/7 | 4/7 | 1/4 | 4/8 | 1/3 | 2/5 | 4/10 |
| HeadacheNervous system disorders | 1/3 | 0/4 | 0/3 | 1/7 | 1/7 | 0/4 | 1/8 | 3/3 | 1/5 | 1/10 |
| HypertensionVascular disorders | 0/3 | 0/4 | 0/3 | 2/7 | 1/7 | 3/4 | 1/8 | 0/3 | 3/5 | 4/10 |
| Aspartate aminotransferase increasedInvestigations | 0/3 | 2/4 | 2/3 | 3/7 | 4/7 | 1/4 | 4/8 | 2/3 | 1/5 | 7/10 |
| VomitingGastrointestinal disorders | 1/3 | 1/4 | 1/3 | 1/7 | 2/7 | 1/4 | 1/8 | 2/3 | 2/5 | 4/10 |
| Abdominal painGastrointestinal disorders | 2/3 | 0/4 | 1/3 | 1/7 | 1/7 | 1/4 | 1/8 | 1/3 | 0/5 | 3/10 |
| ConstipationGastrointestinal disorders | 1/3 | 0/4 | 0/3 | 0/7 | 2/7 | 1/4 | 1/8 | 2/3 | 3/5 | 0/10 |
Safety population included all participants treated with at least 1 dose of any study drug. Per planned analysis, baseline characteristics data were collected and reported per study part (not per dose group).
| Age, Continuous(years) | Part 1: CGT9486 (Single-Agent) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg | Part 2e: CGT9486 + Sunitinib | Total |
|---|---|---|---|---|
| Mean | 58.0 ± 11.91 | 64.4 ± 10.43 | 60.1 ± 9.41 | 60.1 ± 10.98 |
| Sex: Female, Male(Participants) | Part 1: CGT9486 (Single-Agent) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg | Part 2e: CGT9486 + Sunitinib | Total |
|---|---|---|---|---|
| Female | 9 | 3 | 8 | 20 |
| Male | 15 | 9 | 7 | 31 |
| Ethnicity (NIH/OMB)(Participants) | Part 1: CGT9486 (Single-Agent) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg | Part 2e: CGT9486 + Sunitinib | Total |
|---|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 1 | 3 |
| Not Hispanic or Latino | 23 | 11 | 14 | 48 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Part 1: CGT9486 (Single-Agent) | Part 2b: CGT9486 500 mg QD + Pexidartinib 600 mg | Part 2e: CGT9486 + Sunitinib | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 2 | 0 | 2 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 3 | 1 | 5 |
| White | 21 | 9 | 12 | 42 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
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Studies of the drugs tested here: Pexidartinib · Sunitinib
Gastrointestinal Stromal Tumors →
Cogent Biosciences, Inc.