Phase I Safety Study of the Drug MM-121 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment

Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort from cohort 1-6. Cohort 1 began at 3.2 mg/kg IV QW and the dose escalated in separate cohorts from 6 mg/kg IV QW, 10 mg/kg IV QW, 15 mg/kg IV QW, 20 mg/kg IV QW, to the highest scheduled testing dose at 40 mg/kg one-time loading dose on cycle 1, week 1 followed by 20 mg/kg IV QW maintenance doses. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose and was used to open the expansion cohort.

Time frame: From date of first dose to 30 days after termination, the longest 47 weeks

Population: All participants in the 6 cohorts of dose escalation

To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response is defined as a \>20% decrease in tumor burden from baseline and a Complete Response is defined as complete disappearance of tumor burden from baseline. Duration of response is defined as the length of time in weeks from observation of response until progression. NOTE: because no patients experienced an objective response as shown below, duration of response is not presented. No duration of response could be measured.

Time frame: Time from first dose to date of progression, with a median of 7.1 weeks

To establish the safety of escalating doses of MM-121 administered as a monotherapy in order to determine the recommended phase 2 dose. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD to be used for the expansion cohort. DLTs were not measured in the Expansion Cohort.

Time frame: From date of first dose to 30 days after termination, the longest 47 weeks

Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. The maximum observed concentration (Cmax) is presented and was calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg). Immunogenicity data is not available.

Time frame: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients

Population: All patients. NOTE: There are 22 patients included in the final cohort (4 patients in dose escalation portion Cohort 6 + 18 patients in Expansion Cohort), as PK analysis was performed per dose level and not per cohort. Cohort 6 and the Expansion Cohort were administered the same dose, and therefore the analysis reflects all 22 patients.

Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. The AUC is presented and was calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg).

Time frame: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients

Population: All patients. NOTE: There are 22 patients included in the final cohort (4 patients in dose escalation portion Cohort 6 + 18 patients in Expansion Cohort), as PK analysis was performed per dose level and not per cohort. Cohort 6 and the Expansion Cohort were administered the same dose, and therefore the analysis reflects all 22 patients.