RMC-5552 for Glioblastoma

Overseen By Neuro-Oncology New Patient Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nicholas Butowski

Must not be taking: mTOR inhibitors, PI3K inhibitors

Disqualifiers: Uncontrolled hypertension, Diabetes, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug, RMC-5552, to determine its safety, effectiveness, and optimal dose for treating glioblastoma, a type of brain cancer that has recurred after treatment. RMC-5552 is designed to block certain proteins that promote cancer cell growth. The study seeks individuals whose glioblastoma has returned after standard treatments, regardless of prior surgery. Participants will receive varying doses of RMC-5552 to identify the most effective and safe amount. Those whose cancer has returned and are not currently undergoing other cancer treatments might be suitable for this trial. As a Phase 1 trial, this research aims to understand how RMC-5552 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

Yes, you will need to stop certain medications before joining the trial. You must complete chemotherapy or specific inhibitors at least 2 weeks or 5 half-lives before starting, and biologics, hormonal therapy, and immunotherapy at least 4 weeks before starting the trial. There are also specific requirements for nitrosourea and mitomycin C, which must be stopped 6 weeks before the trial.

Is there any evidence suggesting that RMC-5552 is likely to be safe for humans?

Research has shown that RMC-5552 is a type of drug called an mTOR inhibitor, which targets proteins that help cancer cells grow. In earlier studies, researchers tested RMC-5552 to determine the best dose and assess patient tolerance. These studies aim to balance the drug's effectiveness with its safety.

While detailed safety information is not yet available, the phase 1 trial status of RMC-5552 indicates ongoing careful study of its safety in humans. At this stage, researchers focus on understanding patient reactions and potential side effects.

So far, the studies aim to ensure the treatment's safety before progressing to larger trials. Some side effects may occur, but researchers are working to find the safest dose. This process helps ensure any treatment is as safe as possible for future use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

Unlike the standard treatments for glioblastoma, which typically include surgery, radiation, and chemotherapy, RMC-5552 is a targeted therapy that works by inhibiting a protein called mTORC1, which plays a role in tumor growth. This drug is administered intravenously and is designed to be more precise in attacking cancer cells while sparing healthy ones, potentially leading to fewer side effects. Researchers are excited about RMC-5552 because its novel mechanism could offer a new avenue for those with recurrent glioblastoma, particularly for patients who may not be candidates for surgery.

What evidence suggests that RMC-5552 might be an effective treatment for glioblastoma?

Research has shown that RMC-5552 blocks a protein that aids cancer cell growth, making it a promising treatment for glioblastoma, a challenging brain cancer. This trial will explore different dosing strategies of RMC-5552. Early results suggest that inhibiting this protein can slow or even halt tumor growth. While detailed human data is still being gathered, targeting this protein has shown potential in cancer treatment. Since glioblastoma often recurs after treatment, new options like RMC-5552 are being explored to improve patient outcomes. ^{1 2 4 6 7}

Who Is on the Research Team?

Nicholas Butowski, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Adults with a first recurrence of glioblastoma, who've completed standard treatments including radiation and chemotherapy. They must have measurable disease per RANO criteria, adequate organ function, and no major health issues that could interfere with the trial. Participants should not be pregnant or breastfeeding and must agree to use effective contraception.

Inclusion Criteria

I finished radiation therapy at least 12 weeks ago.

I finished my chemotherapy or tyrosine kinase inhibitor treatment at least 2 weeks ago.

Participants must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

I still have side effects from previous cancer treatments.

I have not had a stroke or mini-stroke in the past 6 months.

I have previously been treated with an mTOR or PI3K inhibitor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation

Non-surgical patients receive RMC-5552 intravenously in 21-day cycles to determine the maximum tolerated dose

Up to 1 cycle (21 days)

Weekly visits for drug administration

Dose Expansion

Surgical patients receive a single dose of RMC-5552 prior to surgery, followed by weekly doses post-surgery in 21-day cycles

3-6 weeks post-surgery recovery, then ongoing

Pre-surgery and weekly post-surgery visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• RMC-5552

Trial Overview The trial is testing RMC-5552, an mTOR inhibitor believed to stop cancer cell growth by preventing the formation of mTOR proteins. It's for patients whose glioblastoma has returned after initial treatment. The study will determine the safest dose, side effects, and potential effectiveness.

How Is the Trial Designed?

Group I: Cohort C (Dose Expansion, Recurrent Non-surgical GBM) Experimental Treatment 1 Intervention

Participants will be given the RP2D of RMC-5552 weekly in 21-day cycles until disease progression or unacceptable toxicity

Group II: Cohort B (Dose Expansion, Recurrent Surgical GBM) Experimental Treatment 1 Intervention

Participants will receive a single dose of RMC-5552 at the RP2D approximately 4 hours prior to participants' scheduled surgical resection as part of standard of care. After recovering from surgery (about 3-6 weeks), participants will continue receiving RMC-5552 weekly in 21-day cycles until disease progression or unacceptable toxicity.

Group III: Cohort A2 (Dose Escalation, Recurrent Non-surgical GBM) Experimental Treatment 1 Intervention

Participants receive dose level 2 (12 mg) of RMC-5552 administered intravenously if the toxicity profile from participants in dose level 1 (A1) is acceptable. Participants will receive RMC-5552 weekly in 21-day cycles until disease progression or unacceptable toxicity.

Group IV: Cohort A 1(Dose Escalation, Recurrent Non-surgical GBM) Experimental Treatment 1 Intervention

Participants will start at dose level 1 (6 mg) of RMC-5552 administered intravenously. Participants will receive RMC-5552 weekly in 21-day cycles until disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Nicholas Butowski

Lead Sponsor

Trials

3

Recruited

130+

Revolution Medicines, Inc.

Industry Sponsor

Trials

14

Recruited

4,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase II trial involving 49 patients with recurrent glioblastoma and EGFR amplification, dacomitinib showed limited efficacy, with a 6-month progression-free survival rate of only 10.6%.

The treatment was associated with significant adverse effects, as 40.8% of patients experienced grade 3-4 drug-related side effects, primarily diarrhea and rash, highlighting the need for careful patient selection based on molecular characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification. Sepúlveda-Sánchez, JM., Vaz, MÁ., Balañá, C., et al.[2022]

In a phase II trial involving 21 recurrent glioblastoma patients with EGFR amplification, GC1118 showed a low 6-month progression-free survival rate of only 5.6%, indicating limited efficacy in this patient population.

Despite not meeting the primary endpoint, the study found that GC1118 treatment was well tolerated, with skin rash as the most common side effect, and it upregulated immune-related signatures in tumors, suggesting potential immune-mediated antitumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, phase II trial of GC1118, a novel anti-EGFR antibody, for recurrent glioblastoma patients with EGFR amplification. Choi, SW., Jung, HA., Cho, HJ., et al.[2023]

An atypical protein kinase C inhibitor was found to induce rapid apoptosis in glioblastoma cells expressing the mutant EGFRvIII, with an effective concentration (IC50) of 16 microM.

The apoptosis caused by this inhibitor occurs through a caspase-independent mechanism, suggesting a novel pathway for targeting glioblastoma cells that are resistant to standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of apoptosis in glioblastoma cells by an atypical protein kinase C pseudosubstrate peptide. Lorimer, IA., Parolin, DA., Lavictoire, SJ.[2018]

Current standard treatment for glioblastoma, which includes surgery and temozolomide, results in a median survival of only 12-14 months, highlighting the urgent need for new therapies.

Recent studies on targeted agents like bevacizumab show potential clinical benefits, and ongoing research is exploring various molecular targets and inhibitors to improve treatment outcomes for glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathway inhibition: emerging molecular targets for treating glioblastoma. Wick, W., Weller, M., Weiler, M., et al.[2022]

In a phase II trial involving 56 patients with recurrent glioblastoma (GBM) enriched for EGFR gene amplification, dacomitinib showed effective penetration into tumors, but only 14.3% of patients experienced a clinical benefit lasting at least 6 months.

The presence of specific EGFR mutations (EGFRvIII or EGFR ECD missense mutations) did not predict clinical benefit from dacomitinib, suggesting that alternative biomarkers, such as RNA signatures in circulating extracellular vesicles, may be more promising for identifying patients who could respond to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring Predictors of Response to Dacomitinib in EGFR-Amplified Recurrent Glioblastoma. Chi, AS., Cahill, DP., Reardon, DA., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05557292

RMC-5552 Monotherapy in Adult Subjects With Recurrent ... This phase I/Ib trial tests the side effects, best dose, tolerability, and effectiveness of RMC-5552 in treating patients with glioblastoma that has come ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/glioblastoma

UCSF Glioblastoma Clinical Trials — San Francisco Bay ... This phase I/Ib trial tests the side effects, best dose, tolerability, and effectiveness of RMC-5552 in treating patients with glioblastoma that ...

3. cancer.gov cancer.gov/clinicaltrials/NCI-2022-07698

RMC-5552 for the Treatment of Recurrent Glioblastoma - NCI This phase I/Ib trial tests the side effects, best dose, tolerability, and effectiveness of RMC-5552 in treating patients with glioblastoma that has come ...

4. gatewaycr.org gatewaycr.org/for-researchers/clinical-trials/rmc-5552-in-adults-with-recurrent-glioblastoma/

RMC-5552 in Adults with Recurrent Glioblastoma Summary: Despite current treatment with surgery, radiation, and chemotherapy, glioblastoma (GBM) will inevitably recur within 6 to 13 months of treatment.

5. withpower.com withpower.com/trial/phase-1-recurrence-10-2022-a7763

RMC-5552 for Glioblastoma Current standard treatment for glioblastoma, which includes surgery and temozolomide, results in a median survival of only 12-14 months, highlighting the urgent ...

6. braintumorcenter.ucsf.edu braintumorcenter.ucsf.edu/clinical-trial/phase-iib-open-label-dose-escalation-study-rmc-5552-monotherapy-adult-subjects

A Phase I/Ib, Open-Label, Dose-Escalation Study of RMC- ... This single-center Phase I/Ib study in recurrent glioblastoma (GBM) aims to establish a recommended phase 2 dose of the mTOR inhibitor RMC-552 in GBM ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9841523/

Discovery of RMC-5552, a Selective Bi-Steric Inhibitor of ... In this report, we describe the discovery and preclinical profile of the development candidate RMC-5552 and the in vivo preclinical tool compound RMC-6272. We ...