First Patient With Solid Tumors Dosed in Phase 1/2 Trial of MRT-2359

A phase 1/2 clinical trial evaluating treatment with MRT-2359 in MYC-driven solid tumors has dosed its first patient and looks to improve early signals of clinical activity.

The first patient has been dosed in the phase 1/2 clinical trial (NCT05546268) of MRT-2359 in patients with MYC-driven solid tumors, including lung cancer, according to Monte Rosa Therapeutics, Inc.1

MRT-2359 is a potent, selective, orally bioavailable GSPT1-directed molecular glue degrader. The agent is designed to induce an interaction and disrupt protein synthesis in MYC-driven tumors, which leads to anti-tumor activity.

“MYC transcription factors are well-defined drivers of human cancers, and disrupting protein translation has emerged as a promising path to address this highly prevalent disease pathway. Dosing the first patient is a significant milestone in developing MRT-2359 as a therapeutic option for MYC-driven cancers,” said Filip Janku, MD, PhD, chief medical officer of Monte Rosa, in the press release. “We have designed our phase 1 trial to move efficiently through dose escalation and, by focusing on tumor types where MYC expression is prevalent, to improve our chances of seeing early signals of clinical activity. We are encouraged by the strong preclinical data and hope that MRT-2359 will make a meaningful difference in the lives of patients.”

This open-label, multicenter, phase 1/2 trial will enroll approximately 133 patients with previously treated, select solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), high-grade neuroendocrine cancer of any primary site, diffuse large B-cell lymphoma (DLBCL), and tumors with L-MYC or N-MYC amplification.2

Patients enrolled in the trial will receive escalating doses of MRT-2359 to determine safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of MRT-2359. Once the MTD and/or RP2D is identified, additional patients will be enrolled into the phase 2 portion of the study, which includes molecular biomarkers stratification or selection, namely mRNA expression, or amplification of L-MYC and N-MYC genes.

In the phase 1 portion of the study evaluating the MTD and RP2D of MRT-2359, patients will be included if they have NSCLC, SCLC, DLBCL, high-grade neuroendocrine cancer of any primary site, or any solid tumors with L-MYC or N-MYC amplification. Here, patients will be administered MRT-2359 orally and once a day on days 1 through 5 and days 15 through 19 of a 28-day cycle.

When investigators determine the RP2D, the anti-tumor activity of MRT-2359 will be assessed in the phase 2 portion of the study, which includes molecular biomarkers for stratification and selection. Phase 2 will enroll patients with any solid tumors with L-MYC or N-MYC known amplification, NSCLC, or SCLC with known L-MYC or N-MYC mRNA expression status. Those enrolled will be administered oral MRT-2359 once a day on days 1 through 5 and days 15 through 19 of a 28-day cycle.

For both phase 1 and phase 2 of the trial, patients must have a selected advanced solid tumor or DLBCL who have no further standard therapeutic options available, a life expectancy of ≥ 3 months, an ECOG performance status ≤ 2, measurable disease by RECIST 1.1, and adequate organ function.

The primary end points which will be evaluated in phase 1 are the safety and tolerability of MRT-2359 over a 28-day cycle by the occurrence and frequency of dose limiting toxicities (DLTs) for determination of the MTD and/or RP2D. In phase 2, the primary end point is to evaluate the preliminary anti-tumor activity of MRT-2359 by overall response rate (ORR) as determined by RECIST 1.1.

Secondary end points for phase 1 include safety and tolerability of MRT-2359, preliminary anti-tumor activity, ORR, duration of response for complete response and partial response, disease control rate, progression-free survival, overall survival, and pharmacokinetics (PK). The secondary end points investigated in phase 2 include to examine the safety and tolerability of MRT-2359, additional measures of the preliminary anti-tumor activity, and to further characterize the PK profile.

The trial is currently enrolling patients in Texas and has an estimated study completion date of November 2027.

REFERENCES:
Monte Rosa Therapeutics announces first patient dosed in phase 1/2 clinical trial evaluating MRT-2359, a GSPT1-directed molecular glue degrader, for treatment of MYC-driven tumors. News release. Monte Rosa Therapeutics, Inc. November 1, 2022. Accessed November 2, 2022. https://bit.ly/3TOHIBz
Study of oral MRT-2359 in selected cancer patients. ClinicalTrials.org. Updated October 28, 2022. Accessed November 2, 2022. https://clinicaltrials.gov/ct2/show/NCT05546268?term=MRT-2359&draw=2&rank=1