A Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation

DLTs were defined as protocol-defined toxicities occurring up to and including on Day 28, except those with a clear alternative explanation. Toxicities with a clear alternative explanation (e.g., due to disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination could have been deemed non-DLTs.

An adverse event (AE) was defined any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of either study drug until 104 days after the last dose of study treatment or start of new anticancer therapy.

An AE was defined any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of either study drug until 104 days after the last dose of study treatment or start of new anticancer therapy.

During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered.

During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. Cmax was defined as the maximum plasma concentration of INCB099280. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.

During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. Cmax,ss was defined as the maximum plasma concentration of INCB099280 at steady state. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.

During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. Cmin,ss was defined as the minimum plasma concentration of INCB099280 at steady state. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.

During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. tmax was defined as the time to the maximum concentration of INCB099280. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.

During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. AUC0-tau was defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval of INCB099280. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.

During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. CLss/F was defined as the apparent oral dose clearance of INCB099280 at steady state. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.

Objective response was defined as having a best overall response of complete response (CR) or partial response (PR) assessed per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) by the investigator. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.

Disease control was defined as defined as having a best overall response of CR, PR, or stable disease (SD) ≥15 weeks (from the start of treatment) assessed per RECIST v1.1 by the investigator. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

Duration of response was defined as the time from the first CR or PR until disease progression (assessed per RECIST v1.1 by the investigator) or death from any cause, whichever occurred earlier. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.

≥6-month and ≥12-month PFS was defined as the absence of disease progression (assessed per RECIST v1.1 by the investigator) or death from any cause from the start of treatment to ≥6 or ≥12 months after treatment. A Kaplan-Meier estimate of PFS is an estimate of the probability that a participant will remain alive and free from disease progression (or relapse) at a given time point after starting treatment.