A Study of INCMGA00012 in Metastatic Merkel Cell Carcinoma (POD1UM-201)

ORR was defined as the percentage of participants with a confirmed overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as determined by Independent Central Radiographic Review (ICR), at any post-Baseline visit until the first progressive disease (PD) or new anti-cancer therapy. 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.

Time frame: up to 26.8 months

Population: Full Analysis Set (FAS): all participants enrolled in the study who received at least 1 dose of study drug as of 15 October 2020 (selected to allow for at least 60 chemotherapy-naïve participants to be followed for at least 6 months after first response assessment). Analysis was based on the chemotherapy-naïve subset of the FAS. Confidence intervals (CIs) were calculated based on the exact method for binomial distributions.

DCR was defined as the percentage of participants with a confirmed overall response (CR and PR) or stable disease (SD) (non-CR/non-PD) lasting at least 6 months from the start of treatment, until the first PD or new anti-cancer therapy, per RECIST v1.1 as determined by ICR. 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.

Time frame: up to 57.1 months

Population: Safety Evaluable Population. Analysis was based on the chemotherapy-naïve subset of the population. CIs were calculated based on the exact method for binomial distributions.

DOR was defined as the time from an initial objective response (CR or PR) per RECIST v1.1 until PD, or death due to any cause, as determined by ICR. 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. A Kaplan-Meier estimate (estimated median) of the distribution function is reported.

Time frame: up to 55.3 months

Population: Safety Evaluable Population: all enrolled participants who received at least 1 dose of study drug. Analysis was based on the chemotherapy-naïve subset of the population. Only those participants who had confirmed CR or PR prior to PD or start of new anticancer therapy were assessed. The 95% CI was calculated using the Brookmeyer and Crowley's method and Klein and Moeschberger's method with log-log transformation.

AUC0-t was defined as the area under the plasma concentration-time curve from time zero to time t.

Time frame: preinfusion, 10 minutes postinfusion (± 10 minutes), and 4 hours postinfusion (± 10 minutes) on Day 1 of Cycle 1

Population: PK Evaluable Population

Cmax was defined as the maximum observed plasma concentration.

Time frame: preinfusion, 10 minutes postinfusion (± 10 minutes), and 4 hours postinfusion (± 10 minutes) on Day 1 of Cycle 1

Population: Pharmacokinetic (PK) Evaluable Population: all participants who received at least 1 dose of study drug and have provided a Baseline and at least 1 post-dose PK sample

Cmin was defined as the minimum observed plasma concentration over the dose interval.

Time frame: preinfusion, 10 minutes postinfusion (± 10 minutes), and 4 hours postinfusion (± 10 minutes) on Day 1 of Cycle 1

Population: PK Evaluable Population

An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and 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 either an AE reported for the first time or a worsening of a pre-existing event after the first dose of study drug until 90 days after the last dose of study drug. An AE with onset on/after starting a new anticancer therapy was not summarized as a TEAE.

Time frame: up to 846 days (up to approximately 2.3 years)

Population: Safety Evaluable Population

Overall survival was defined as the time in months between the first dose date (Day 1) and the date of death due to any cause.

Time frame: up to 60.4 months

Population: Safety Evaluable Population. Analysis was based on the chemotherapy-naïve subset of the population. Median overall survival time was estimated using the Kaplan-Meier method. CI for median overall survival time was calculated using the method of Brookmeyer and Crowley.

According to RESIST v1.1, PFS was defined the time from the start of therapy until disease progression, or death due to any cause, as determined by ICR. Evaluation of target lesions: PD: ≥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. (Note: the appearance of one or more new lesions is also considered PD). Evaluation of non-target lesions: PD: Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered PD).

Time frame: up to 57.1 months

Population: Safety Evaluable Population. Analysis was based on the chemotherapy-naïve subset of the population. Median PFS time was estimated using the Kaplan-Meier method. The CI for median PFS time was calculated using the method of Brookmeyer and Crowley.