RSC-1255 for Advanced Cancers

Recruiting at 8 trial locations

Overseen By Bonnie Wettersten, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: RasCal Therapeutics, Inc.

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

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

Compensation: Varies

Number of Visits: Unknown

134 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, RSC-1255 (a KRAS inhibitor and V-ATPase inhibitor), for individuals with advanced cancers who have not responded to standard therapies or cannot tolerate them. The study aims to determine the appropriate dose and assess the treatment's safety and effectiveness. It suits those whose cancer has progressed after other treatments and who have measurable tumors. Participants must not be on other cancer treatments when joining the trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that RSC-1255 is likely to be safe for humans?

Research has shown that RSC-1255 appears to be safe. In studies with mice, this compound, also known as 249C, stopped tumor growth without causing harmful side effects. This suggests it might also be safe for humans. However, since RSC-1255 remains in the early stages of human testing, further research is needed to confirm its safety. Early trials like this one are crucial for determining the right dose and monitoring any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

RSC-1255 is unique because it represents a novel approach to treating advanced cancers by targeting specific cancer cell pathways that current treatments might not address. Unlike conventional therapies such as chemotherapy or radiation, which can affect both cancerous and healthy cells, RSC-1255 is designed to hone in on cancer cells more precisely, potentially reducing side effects and improving patient outcomes. Researchers are excited about RSC-1255 because it may offer a new mechanism of action that could enhance effectiveness against resistant cancer types, giving new hope to patients who haven't responded to existing treatments.

What evidence suggests that RSC-1255 might be an effective treatment for advanced cancers?

Research has shown that RSC-1255, also known as compound 249C, may help treat advanced cancers. Studies in mice found that this compound can stop tumors from growing without causing harmful side effects, particularly in cancers with a KRAS mutation. KRAS is a gene that often changes in many cancers, making them difficult to treat. Previous research suggests that targeting KRAS mutations can lead to better treatment results. Although more studies in humans are needed, these early findings offer promise for people with advanced solid tumors. Participants in this trial will receive RSC-1255 to further evaluate its effectiveness and safety in humans. ^{1 2 3 5 6}

Who Is on the Research Team?

Pamela Munster, MD

Principal Investigator

RasCal Therapeutics, Inc.

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• RSC-1255

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.

How Is the Trial Designed?

Group I: RSC-1255 Treatment Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

RasCal Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

130+

Published Research Related to This Trial

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]

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]

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]

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 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 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]

The study identified HER2 copy number gain as a significant mechanism of resistance in lung cancer patients treated with the KRASG12C inhibitor sotorasib, highlighting the complexity of targeting KRAS mutations.

Combining KRASG12C inhibition with SHP2 inhibition was found to effectively overcome this resistance in both laboratory and animal models, suggesting a potential strategy for improving treatment outcomes in patients with KRASG12C mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2 mediates clinical resistance to the KRASG12C inhibitor sotorasib, which is overcome by co-targeting SHP2. Ho, CSL., Tüns, AI., Schildhaus, HU., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-1-neoplasms-1-2021-0f9d0

RSC-1255 for Advanced Cancers 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 ...

2. nature.com nature.com/articles/s41587-022-01386-z

Ras-mutant cancers are sensitive to small molecule ... 249C potently inhibits tumor growth without adverse side effects in mouse xenografts of KRAS-driven lung and colon cancers.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7999304/

Targeting KRAS in Cancer: Promising Therapeutic Strategies However, some recent findings show promising results indicating that we are one step closer to developing an effective inhibitor that directly targets KRAS.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11572139/

An updated overview of K-RAS G12C inhibitors in advanced ... Clinical trials have shown that KRAS G12C inhibitors improved objective response rates and progression-free survival compared with standard treatments. These ...

5. science.org science.org/doi/10.1126/scitranslmed.adt5511

An allele-agnostic mutant-KRAS inhibitor suppresses ... MRTX1133 treatment of KRASG12D PDAC cell lines showed a potent cancer cell–intrinsic antiproliferative effect and an anticancer immune response.

6. jto.org jto.org/article/S1556-0864(24)00762-7/fulltext

Efficacy and Safety of KRAS G12C Inhibitor IBI351 ... IBI351 was well-tolerated in patients with advanced solid tumors harboring KRAS G12C mutation, demonstrating promising efficacy and durable ...