RMC-5552 Monotherapy in Adult Subjects With Recurrent Glioblastoma

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of mTORC1 kinase inhibitor RMC-5552 (RMC- 5552). (Cohort A). II. To characterize the safety and tolerability of RMC-5552 monotherapy. (Cohort A). III. To characterize the pharmacokinetics (PK) of RMC-5552 after a single dose of RMC-5552 prior to surgical resection. (Cohort B). IV. To evaluate the preliminary antitumor effect of RMC-5552. (Cohort C). SECONDARY OBJECTIVES: I. To measure the pharmacokinetics (PK) of RMC-5552. (Cohort A). II. To evaluate the preliminary antitumor effect of RMC-5552. (Cohort A). III. To assess pharmacodynamic (PD) markers of drug activity, including biochemical markers of mTORC1 pathway inhibition in tumor tissue. (Cohort B). IV. To characterize the safety and tolerability of RMC-5552 monotherapy. (Cohort B). V. To evaluate the preliminary antitumor effect of RMC-5552 in recurrent glioblastoma multiforme (GBM). (Cohort B). VI. To characterize the safety and tolerability of RMC-5552 monotherapy. (Cohort C). VII. To measure the PK of RMC-5552. (Cohort C). OUTLINE: This is a phase I, dose-escalation study (Cohort A) followed by a phase Ib study (Cohorts B and C). Participants are assigned to 1 of 3 cohorts. COHORT A: Non-surgical patients receive RMC-5552 intravenously (IV) on study. Patients undergo a pulmonary function test and chest x-ray during screening. Patients also undergo a brain magnetic resonance imaging (MRI) throughout the trial. Patents undergo blood sample collection on study. \*\*\*\* STUDY CLOSED TO ACCRUAL BEFORE ENROLLMENT ON COHORTS B AND C COULD BEGIN \*\*\* PLANNED COHORT B: Surgical patients receive a single dose of RP2D RMC-5552 IV prior to standard of care surgery and then on study. Patients undergo a pulmonary function test and chest x-ray during screening. Patients also undergo a brain MRI throughout the trial. Patents undergo blood sample collection on study. PLANNED COHORT C: Non-surgical patients receive RP2D of RMC-5552 IV on study. Patients undergo a pulmonary function test and chest x-ray during screening. Patients also undergo a brain MRI throughout the trial. Patents undergo blood sample collection on study. Participants will be followed after their last treatment with RMC-5552 until the participant voluntarily withdraws consent, or until death; whichever comes first.