FMC-376 for Solid Tumors

(PROSPER Trial)

Recruiting at 22 trial locations

Overseen By Medical Lead

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Frontier Medicines Corporation

Disqualifiers: Leptomeningeal disease, Carcinomatous meningitis, others

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

Compensation: Varies

Number of Visits: Unknown

403 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called FMC-376 for individuals with advanced solid tumors that have a specific gene change known as the KRAS G12C mutation. Researchers aim to evaluate the effectiveness of different doses of FMC-376 in managing these tumors. The study will occur in three parts, focusing on dose adjustment and expansion. Individuals diagnosed with these tumors who have not found success with standard treatments may be suitable candidates for the trial. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that FMC-376 is likely to be safe for humans?

Research shows that FMC-376 is a new treatment being tested for advanced solid tumors with a specific mutation called KRAS G12C. Earlier studies examined its ability to overcome resistance in these cancers. Importantly, FMC-376 has been part of studies to determine the safest and most effective dose.

So far, studies have found that FMC-376 is generally well-tolerated, meaning most people don't experience serious problems. Some side effects have been reported, which is common when testing new treatments. The treatment's safety is still under evaluation, as it is in the early stages of testing. However, its progression suggests no major safety issues have been identified so far.

For those considering joining the trial, safety remains a top priority. Researchers will monitor for any unwanted side effects and adjust treatment as needed to ensure participant safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

FMC-376 is unique because it introduces a novel approach to treating solid tumors by potentially targeting specific pathways that current treatments, like chemotherapy and radiation, might not address as precisely. While most treatments for solid tumors work by killing rapidly dividing cells, FMC-376 is designed to selectively target tumor cells, which could lead to fewer side effects and improved patient outcomes. Researchers are particularly excited about its potential for dose escalation and expansion, which could allow for more tailored and effective treatment regimens compared to the broader approaches of existing therapies.

What evidence suggests that FMC-376 might be an effective treatment for advanced solid tumors?

Research has shown that FMC-376, the investigational treatment in this trial, could effectively treat advanced solid tumors with the KRAS G12C mutation. In lab studies, FMC-376 successfully stopped tumor growth and improved the health of cancer cells with this mutation. It blocks both active and inactive forms of the KRAS G12C protein, which often increases in hard-to-treat cancers. Early results also indicate that FMC-376 can strongly block the pathways cancer cells use to grow and spread. These findings suggest that FMC-376 might be a strong option for addressing tumors with challenging mutations. ^{1 2 4 6 7}

Who Is on the Research Team?

Medical Lead

Principal Investigator

Frontier Medicines Corporation

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have a specific genetic change called KRAS G12C mutation. They should have tried standard treatments without success or can't tolerate them, and their blood, kidney, and liver functions must be stable. Participants need to be fairly active and well (ECOG status 0 or 1) and agree not to join other drug studies.

Inclusion Criteria

My blood, kidney, and liver tests are within normal ranges.

Agrees not to participate in another interventional study while receiving study drug

My condition worsened or I couldn't tolerate the standard treatment, or it was deemed unsuitable for me.

Exclusion Criteria

I do not have any conditions that affect how my body absorbs medication.

My cancer has spread to the lining of my brain or spinal cord.

Known or suspected hypersensitivity to FMC-376 or any components of the study drug

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of FMC-376 to determine the maximum tolerated dose

21 days

Multiple visits (in-person) during each cycle

Dose Expansion

Participants receive the determined dose of FMC-376 to further evaluate safety and efficacy

21-day cycles

Multiple visits (in-person) during each cycle

Cohort Expansion

Participants are treated with FMC-376 to assess clinical activity in specific cohorts

21-day cycles

Multiple visits (in-person) during each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 24 months

What Are the Treatments Tested in This Trial?

Interventions

• FMC-376

Trial Overview FMC-376 is being tested in people with certain types of cancer like colorectal, lung, and pancreatic cancers. The study has three parts: finding the right dose (Phase 1A), confirming this dose in more patients (Phase 1B), and then testing it in specific groups of patients (Phase 2).

How Is the Trial Designed?

Group I: FMC-376 Experimental Treatment 1 Intervention

Dose Escalation, Dose Expansion, and Cohort Expansion; Administered for 21-day cycle

Who Is Running the Clinical Trial?

Frontier Medicines Corporation

Lead Sponsor

Trials

1

Recruited

400+

Published Research Related to This Trial

Capecitabine, an antimetabolite drug used in cancer treatment, can cause rare but serious side effects like myopericarditis, as demonstrated in a case of a 46-year-old woman who experienced chest pain and elevated cardiac troponin levels after her first dose.

Recognizing and treating capecitabine-induced myopericarditis promptly is crucial to prevent severe cardiac complications, highlighting the need for awareness of this potential toxicity in patients undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual case of acute myopericarditis after the first dose of capecitabine: Need for new cardioprotective strategies and risk stratification. Meter, M., Gavran, I., Bajo, D., et al.[2021]

Adjuvant systemic therapy with 5-fluorouracil (5-FU) and folic acid is the established standard for treating stage III colorectal cancer, while new studies suggest that capecitabine may replace this standard treatment.

In metastatic colorectal cancer, combining 5-FU/folic acid with agents like CPT-11 or oxaliplatin (FOLFOX) has shown to significantly improve progression-free survival and overall survival, and targeted therapies like bevacizumab and cetuximab are emerging as effective options that enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant and palliative anticancer treatment of colon carcinoma in 2004]. Medinger, M., Steinbild, S., Mross, K.[2015]

In a study involving six patients and rabbits with VX2 tumors, 5-fluorouracil (5FU) was found to accumulate in tumors, with a significantly longer half-life in tumors (0.4-2.1 hours) compared to its short half-life in blood (5-15 minutes).

The ability to detect free 5FU in tumors using 19F NMR spectroscopy suggests that the extent of 5FU trapping may correlate with patient response to chemotherapy, highlighting the potential of this method for real-time pharmacokinetic analysis in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor trapping of 5-fluorouracil: in vivo 19F NMR spectroscopic pharmacokinetics in tumor-bearing humans and rabbits. Wolf, W., Presant, CA., Servis, KL., et al.[2019]

F10, a polymeric fluoropyrimidine, is significantly more potent than 5-fluorouracil (5-FU), showing a 137-314 fold increase in effectiveness depending on the TP53 mutational status in colorectal cancer cell lines.

The study found that TP53 mutations, especially gain-of-function mutations, lead to increased resistance to 5-FU, but F10 remains effective against these resistant cancer cells, suggesting it could improve treatment outcomes for colorectal cancer patients with TP53 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved potency of F10 relative to 5-fluorouracil in colorectal cancer cells with p53 mutations. Dominijanni, A., Gmeiner, WH.[2022]

Fluorouracil (5-FU) combined with levamisole is the standard treatment for node-positive colon cancer, showing significant benefits in disease-free and overall survival without long-term side effects.

While 5-FU can be enhanced with leucovorin to improve response rates and survival, other combinations like semustine have raised safety concerns, limiting their use despite some initial efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment approaches in colorectal cancer. Grem, JL.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06244771

A Study Evaluating FMC-376 in Participants With KRAS ... The goal of this clinical trial is to evaluate FMC-376 in participants with advanced solid tumors with KRAS G12C mutations. This clinical trial will be ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS3184

Phase 1/2 study of FMC-376 an oral KRAS G12C dual ... Nonclinical pharmacology studies demonstrate that FMC-376 inhibits tumor cell growth and viability in cells harbouring KRAS G12C mutation and ...

3. frontiermeds.com frontiermeds.com/press-release/frontier-medicines-presents-new-data-for-first-in-class-dual-onoff-kras-g12c-inhibitor-fmc-376-at-the-aacr-annual-meeting/

April 9, 2024 In preclinical results, FMC-376 is shown to be highly active in models of G12C inhibitor resistance where ON state KRAS G12C is upregulated. FMC ...

4. firstwordpharma.com firstwordpharma.com/story/6401227

Frontier Medicines Presents Preclinical Data from Three ... FMC-376 demonstrated robust anti-tumor activity across preclinical models and led to deeper inhibition of KRAS downstream pathways compared ...

5. withpower.com withpower.com/trial/phase-2-colorectal-carcinoma-crc-1-2024-15ef2

FMC-376 for Solid Tumors (PROSPER Trial) The goal of this clinical trial is to evaluate FMC-376 in participants with advanced solid tumors with KRAS G12C mutations.

6. dana-farber.org dana-farber.org/clinical-trials/25-170

AN OPEN-LABEL, PHASE 1/2 DOSE ESCALATION ... The goal of this clinical trial is to evaluate FMC-376 in participants with advanced solid tumors with KRAS G12C mutations.

7. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/study00160949

An Open-label, Phase I/II Dose-Escalation, ... An Open-label, Phase I/II Dose-Escalation, Dose Expansion and Cohort Expansion Study Evaluating the Safety, PK and Clinical Activity of FMC-376 in Participants ...