IMCgp100

RFS is defined as the time between randomization and local recurrence, distant recurrence, or death, whichever occurs first

OS is the time from randomization to death due to any cause.

Best response to treatment, with partial molecular response (pMR) defined as a decrease in the allele frequency of the index mutation(s), and complete molecular response (cMR) as no detectable mutation(s)

ctDNA response (defined as ≥0.3 log reduction) in ctDNA-evaluable patients as measured using Signatera assay.

Regression is defined as ≥ 20% reduction in tumor volume. All estimates of rates will be presented with corresponding 95% exact confidence intervals. For regression rate, the method of Atkinson and Brown will be used to allow for the two-stage design.

Progression-free survival (PFS) will be defined as the elapsed time in months from the first date of study treatment until documented disease progression, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, whichever is earlier. For participants who remain alive without progression, follow-up time will be censored at the date of last disease assessment.

The number of participants experiencing treatment-related adverse events (AEs) and serious adverse events (SAEs) in participants receiving protocol therapy will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5, per physician discretion.

Overall survival is defined as the time from randomization to date of death due to any cause.

Number of participants with a dose limiting toxicity, defined as an adverse event (AE) or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment and meets any of the pre-specified criteria.

Objective response rate (ORR) is defined as the percentage of participants with measurable disease with at least 1 visit response of complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an independent central review (ICR). The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline.

The maximum tolerated dose (MTD) for IMCgp100 administered by weekly dosing was determined based on the frequency of dose-limiting toxicity (DLT) occurring during Days 1 to 8. Participants presented at MTD in the dose escalation phase. Abbreviations: ng/kg=nanograms/kilogram

The MTD for IMCgp100 administered by daily dosing was determined based on the frequency of DLT occurring during Days 1 to 8. The 50 mcg dose was the RP2D for daily dosing, as the MTD was not achieved. Abbreviations: mcg=micrograms

Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) with an onset date after the date of first dose and within 30 days after the last administration of study medication in either treatment arm. AEs with missing date of onset were considered treatment emergent.

Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Laboratory parameter abnormalities were graded by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.

Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Laboratory parameter abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.

Twelve lead ECGs were obtained after the participant has rested in a supine position for at least 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator or designated physician occurring at any time on treatment from normal pre-dose.

Vital signs included temperature, blood pressure, respiration rate, and heart rate. Measurements were made after the participant had been resting supine for a minimum of 5 minutes. Blood pressure and heart rate were measured using a recording device with an appropriate cuff size. Temperature and respiration rate were measured as per clinical practice. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.