RSC-1255 for Advanced Cancers

Recruiting in Palo Alto (17 mi)

+8 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: RasCal Therapeutics, Inc.

Disqualifiers: Cancer therapy, Cardiovascular disease, Gilbert's, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests RSC-1255, an oral drug designed to block proteins that help cancer cells grow. It targets adults with advanced solid tumors who have not responded to or cannot tolerate other treatments. The goal is to find a safe dose and see how well the drug works.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be receiving cancer therapy at the time of enrollment.

What data supports the effectiveness of the drug RSC-1255 for advanced cancers?

Research shows that 249C, a component of RSC-1255, is effective against certain KRAS-mutant cancers by targeting V-ATPase, which is crucial for cancer cell survival. It has been shown to inhibit tumor growth in mouse models of KRAS-driven lung and colon cancers without harmful side effects. ^{1 2 3 4 5}

Is RSC-1255 safe for humans?

In studies with mice, the compound 249C, which is the same as RSC-1255, was shown to inhibit tumor growth without causing harmful side effects in models of KRAS-driven lung and colon cancers. ^{1 2 3 6 7}

How is the drug RSC-1255 different from other treatments for advanced cancers?

RSC-1255 is unique because it targets specific KRAS mutations by inhibiting V-ATPase, a protein that helps cancer cells survive by maintaining their internal environment. This approach is different from other treatments that directly target KRAS mutations, offering a new way to treat cancers driven by these mutations, especially KRASG13D and G12V, without significant side effects. ^{1 2 3 7 8}

Research Team

Pamela Munster, MD

Principal Investigator

RasCal Therapeutics, Inc.

Eligibility Criteria

This trial is for adults with advanced solid tumors who have not responded to, or can't tolerate, standard treatments. It's open to those with certain types of cancer like lung and colon cancer, where the tumor can be measured by scans or tests. Participants must be over 18 and in stable condition as judged by ECOG performance status.

Inclusion Criteria

My cancer has worsened despite treatment.

My cancer has not responded to any treatment known to work.

My cancer is advanced or has spread to other parts of my body.

Exclusion Criteria

I am currently undergoing cancer treatment.

I have heart disease or abnormal heart test results.

I do not have any major organ system diseases.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1a: Participants receive RSC-1255 to identify the Maximum Tolerated Dose

Approximately 28 days

Dose Expansion

Phase 1b: Additional participants receive RSC-1255 to further characterize safety and efficacy

Approximately 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 24 months

Treatment Details

Interventions

• RSC-1255 (Other)

Trial Overview RSC-1255 is being tested in two phases: Phase 1a determines the safe dosage level while Phase 1b assesses its safety and effectiveness against various advanced cancers. The study aims to find out if RSC-1255 can help patients whose cancers haven't improved with other treatments.

Participant Groups

Group I: RSC-1255 Treatment Experimental Treatment 2 Interventions

Single Arm Study. All study participants receive RSC-1255.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Sarah Cannon, SCRI Oncology Partners - Health One Denver, CO

Sarah Cannon, SCRI Oncology Partners Nashville, TN

Sarah Cannon, SCRI Oncology Partners, Sidney Kimmel Cancer Center - Thomas Jefferson Hospital Philadelphia, PA

University of California, Los Angles (UCLA) Department of Medicine - Hematology/Oncology Los Angeles, CA

More Trial Locations

Who Is Running the Clinical Trial?

RasCal Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

130+

Findings from Research

249C is a selective cytotoxic agent that targets Ras-mutant cancer cells, which are often difficult to treat.

The mechanism of action involves binding to and inhibiting V-ATPase, an enzyme that plays a crucial role in cancer cell survival and proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific KRAS-Mutant Cancers Are Sensitive to Inhibition of V-type ATPases. [2022]

The compound 249C has been identified as a selective and potent cytotoxic agent against Ras-mutant cancers, particularly effective at nanomolar concentrations, by targeting the V-ATPase enzyme and disrupting essential survival pathways in these cancer cells.

In mouse models, 249C demonstrated significant tumor growth inhibition in KRAS-driven lung and colon cancers, especially in tumors with KRASG13D and G12V mutations, without causing adverse side effects, indicating its potential as a targeted therapy for specific Ras mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ras-mutant cancers are sensitive to small molecule inhibition of V-type ATPases in mice. Tolani, B., Celli, A., Yao, Y., et al.[2023]

KRASG12C is a promising target for treating solid tumors, particularly because it is a common mutation that keeps the KRAS protein in an active form, driving cancer growth.

Recent advancements have led to the FDA's emergency approval of KRASG12C inhibitors like sotorasib and adagrasib for metastatic lung cancer, marking a significant breakthrough in targeting what was once considered an 'undruggable' protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent progress in targeting KRAS mutant cancers with covalent G12C-specific inhibitors. Rathod, LS., Dabhade, PS., Mokale, SN.[2023]

The KRAS inhibitor BI-2852 effectively inhibits ERK phosphorylation, which is crucial for the growth of KRAS-mutant cancer cells, suggesting a potential mechanism for its anti-cancer effects.

This new drug may provide a treatment option for patients with KRAS mutations who do not respond to existing KRASG12C inhibitors currently being tested in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Researchers Reveal Another KRAS Inhibitor. [2020]

KRAS mutations are linked to many types of cancer, and new drugs targeting KRASG12C mutations are showing promise in clinical trials.

The dual RAF-MEK inhibitor VS-6766 has demonstrated early effectiveness as a single agent in treating cancers driven by non-G12C KRAS mutations, indicating its potential as a broader treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Searching for treatments for non-G12C-KRAS mutant cancers. Guo, C., Banerji, U.[2023]

The novel compound KS-19 demonstrated strong antiproliferative activity against KRAS G12C-mutated cancer cells, with an IC50 of 460 to 870 nM, and showed selectivity over other KRAS mutations, indicating its potential as a targeted cancer therapy.

In vivo studies revealed that KS-19 effectively inhibited tumor growth in mice with NCI-H358 xenografts, achieving a tumor growth inhibition of 47%, and exhibited a favorable safety profile without significant toxicity or organ damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of novel Quinazoline-based KRAS G12C inhibitors as potential anticancer agents. Li, L., Zhao, H., Peng, X., et al.[2022]

KRAS G12C mutations are common in non-small-cell lung cancer (NSCLC), occurring in about 30% of cases, and recent developments in allelic-specific KRAS inhibitors offer new treatment options for these patients.

The review discusses not only the current therapies available for advanced NSCLC with KRAS G12C mutations, including PD-(L)1-based therapies and direct KRAS inhibitors, but also addresses potential resistance mechanisms and strategies to overcome them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to manage KRAS G12C-mutated advanced non-small-cell lung cancer. Ricciuti, B., Mira, A., Andrini, E., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Specific KRAS-Mutant Cancers Are Sensitive to Inhibition of V-type ATPases. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Ras-mutant cancers are sensitive to small molecule inhibition of V-type ATPases in mice. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Recent progress in targeting KRAS mutant cancers with covalent G12C-specific inhibitors. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Researchers Reveal Another KRAS Inhibitor. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Searching for treatments for non-G12C-KRAS mutant cancers. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Discovery of novel Quinazoline-based KRAS G12C inhibitors as potential anticancer agents. [2022]

7. England pubmed.ncbi.nlm.nih.gov

How to manage KRAS G12C-mutated advanced non-small-cell lung cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

HER2 mediates clinical resistance to the KRASG12C inhibitor sotorasib, which is overcome by co-targeting SHP2. [2021]