RP-3500 for Solid Cancers

Recruiting at 12 trial locations

Overseen By Gabriela Gomez, MD, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Repare Therapeutics

Must not be taking: QT-prolonging medications

Disqualifiers: Uncontrolled infection, Brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

285 Participants Needed

Trial Summary

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

The trial requires that you stop chemotherapy, small molecule anticancer, or biologic anticancer therapy at least 14 days before starting the study drug. If you are on medications that prolong the QT interval, you may also need to stop those. Other medications are not specifically mentioned, so consult with the trial team for guidance.

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

The trial requires that you stop chemotherapy, small molecule anticancer, or biologic anticancer therapy at least 14 days before starting the study drug. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the idea that RP-3500 for Solid Cancers is an effective drug?

The available research shows that Gemcitabine (Gemzar), which is part of the RP-3500 treatment, has shown effectiveness in treating various solid cancers. For breast cancer, it has demonstrated better outcomes without severe side effects, especially when combined with other drugs, leading to longer survival and delayed disease progression. In non-small cell lung cancer (NSCLC), Gemcitabine combined with other drugs has shown increased effectiveness and fewer side effects compared to standard treatments. These findings suggest that RP-3500, which includes Gemcitabine, can be an effective option for treating solid cancers. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Gemcitabine (Gemzar) for solid cancers?

Gemcitabine (Gemzar) has shown effectiveness in treating various solid tumors, including breast cancer and non-small cell lung cancer, by improving outcomes like survival and time to disease progression when used alone or in combination with other drugs. ^{1 2 3 4 5}

What safety data is available for RP-3500 (camonsertib) and related treatments?

The research provided focuses on the safety and efficacy of Gemcitabine (Gemzar) in various cancer treatments. Gemcitabine has been studied in combination with other agents like interferon alpha, doxorubicin, and platinum compounds for different cancers, including renal cell carcinoma, breast cancer, and non-small-cell lung cancer. The studies report moderate toxicity levels, with common side effects including leukopenia, neutropenia, febrile neutropenia, anemia, mucositis, and diarrhea. However, there is no specific safety data for RP-3500 (camonsertib) or Talazoparib (Talzenna) in the provided research. ^{1 2 6 7 8}

What safety data exists for RP-3500 (camonsertib) and related treatments like Gemcitabine (Gemzar) in humans?

Gemcitabine (Gemzar) has been studied in various cancers and generally shows moderate safety, with some patients experiencing blood-related side effects like low white blood cell counts and anemia, as well as mouth sores and diarrhea. These side effects are considered manageable, and the treatment is often combined with other drugs to improve effectiveness while monitoring for toxicity. ^{1 2 6 7 8}

Is the drug combination of Gemcitabine, RP-3500, and Talazoparib promising for treating solid cancers?

Yes, the combination of Gemcitabine, RP-3500, and Talazoparib is promising for treating solid cancers. Gemcitabine has shown effectiveness in various cancers like breast, lung, and ovarian cancer, often improving survival and response rates when combined with other drugs. This suggests that combining it with RP-3500 and Talazoparib could enhance its effectiveness in treating solid cancers. ^{1 2 3 5 9}

What makes the drug RP-3500 for solid cancers unique?

The drug RP-3500 (camonsertib) is unique because it combines gemcitabine, which has shown effectiveness in various cancers, with talazoparib, a PARP inhibitor that targets cancer cells with specific DNA repair weaknesses, potentially offering a novel mechanism of action and improved outcomes for solid cancers. ^{1 2 3 5 9}

What is the purpose of this trial?

This trial is testing a new oral drug, RP-3500, alone and with other drugs in patients with advanced cancers that have specific genetic mutations. The drug aims to stop cancer cells from fixing themselves, potentially shrinking or stopping the growth of the cancer.

Research Team

Timothy Yap

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with advanced solid tumors and specific ATR inhibitor-sensitizing mutations can join this trial. They must have measurable disease, be in good physical condition (ECOG score of 0 or 1), and able to swallow pills. Participants need proper organ function, acceptable blood counts, and a negative pregnancy test if applicable. Contraception is required during the study and for six months after.

Inclusion Criteria

I have recovered from all side effects of my previous cancer treatments or surgeries.

My cancer does not respond to standard treatments or I cannot tolerate them.

My cancer's biomarker profile is available from a certified lab test.

Exclusion Criteria

I do not have any active, uncontrolled infections including HBV, HCV, HIV, or AIDS.

I have been treated with ATR or DNA-PK inhibitors before.

My liver function is moderately or severely impaired.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Evaluate the safety profile and MTD of RP-3500 (camonsertib) when administered orally, alone and in combination with talazoparib or gemcitabine

Up to 90 days

Expansion Cohorts

Expansion cohorts with RP-3500 (camonsertib) to study the anti-tumor effect and further examine the safety and PK at the RP2D

About 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days after last administration of study intervention

Treatment Details

Interventions

• Gemcitabine Injection [Gemzar]
• RP-3500 (camonsertib)
• Talazoparib

Trial Overview The trial tests RP-3500 (camonsertib) alone or combined with talazoparib or gemcitabine to find the safest high dose for Phase 2 trials. It will assess safety, how the body processes these drugs, their effects on tumors, and overall anti-tumor activity.

Participant Groups

Group I: RP-3500 (camonsertib) with Talazoparib or Gemcitabine Experimental Treatment 3 Interventions

Phase 1: Multiple doses of RP-3500 (camonsertib) for oral administration in combination with talazoparib or gemcitabine

Group II: RP-3500 (camonsertib) alone Experimental Treatment 1 Intervention

Phase 1: Multiple doses of RP-3500 (camonsertib) for oral administration alone

Group III: Expansion cohorts with RP-3500 (camonsertib) Experimental Treatment 1 Intervention

Phase 2: Expansion cohorts with RP-3500 (camonsertib)

Gemcitabine Injection [Gemzar] is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Non-small cell lung cancer
• Ovarian cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Non-small cell lung cancer
• Ovarian cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Non-small cell lung cancer
• Ovarian cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Non-small cell lung cancer
• Ovarian cancer

Who Is Running the Clinical Trial?

Repare Therapeutics

Lead Sponsor

Trials

10

Recruited

1,300+

Roche Pharma AG

Industry Sponsor

Trials

413

Recruited

430,000+

Dr. Thomas Schinecker

Roche Pharma AG

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Dr. Levi Garraway

Roche Pharma AG

Chief Medical Officer since 2019

MD from University of California, San Francisco

Findings from Research

In a phase I clinical trial involving 13 patients with metastatic renal cell carcinoma, the combination of gemcitabine and rHuIFN-alpha2b showed significant hematologic toxicity, particularly at higher doses, including severe anemia and neutropenia.

The study determined that the maximal tolerated dose was gemcitabine 600 mg/m2 weekly and rHuIFN-alpha2b 1.0 MU/m2 three times a week, leading to the conclusion that further investigation of this combination is not recommended due to the associated toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of weekly gemcitabine and subcutaneous interferon alpha in patients with refractory renal cell carcinoma. Perez-Zincer, F., Olencki, T., Budd, GT., et al.[2022]

Gemcitabine (Gemzar) has shown significant antitumor activity in breast cancer treatment, providing better outcomes without excessive toxicity, making it a promising option for patients.

In combination with paclitaxel, gemcitabine has established itself as a first-line treatment, improving response rates and survival, and is currently being investigated for its role in early-stage breast cancer as part of neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating gemcitabine into breast cancer therapy. Yardley, DA.[2022]

Gemcitabine, a nucleoside analogue, shows promise in treating non-small cell lung cancer (NSCLC) and has been evaluated in economic studies across multiple countries, indicating it may be cost-effective compared to other treatments.

The economic evaluations suggest that gemcitabine can be administered safely in an outpatient setting with a lower side-effect profile, which contributes to its potential cost savings in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the pharmacoeconomic research on gemcitabine in the treatment of advanced non-small cell lung cancer. Minshall, ME., Liepa, AM.[2022]

Gemcitabine, a nucleoside analog, inhibits DNA synthesis and shows potential synergy with other antimetabolites like 5-fluorouracil, making it a promising treatment for solid tumors.

In a phase I study involving eight patients, the main side effect observed was myelosuppression, and the study aims to establish the maximum tolerated doses of gemcitabine when combined with UFT and oral calcium folinate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and UFT plus oral calcium folinate: phase I study. Philip, PA., Ibrahim, D., Zalupski, M., et al.[2022]

Gemcitabine was initially approved for treating advanced non-small-cell lung cancer (NSCLC) in combination with cisplatin, but research has shifted towards combining it with newer drugs that may offer better efficacy and fewer side effects.

The article reviews the effectiveness of non-cisplatin-based combinations of gemcitabine with other agents, highlighting the ongoing evolution in treatment strategies for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in treatment of inoperable NSCLC: gemcitabine doublets--a promising alternative. Cappuzzo, F., Rocha Lima, CM., Sherman, CA., et al.[2022]

In a study involving 39 chemotherapy-naive patients with stage IIIB breast cancer, the combination of gemcitabine and doxorubicin as neoadjuvant therapy resulted in a high overall response rate of 95%, with 18% achieving a complete response and 77% a partial response.

The treatment was associated with moderate toxicity, including hematologic issues like neutropenia and leukopenia, but overall, 83% of treatment cycles were administered at full dose, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of neoadjuvant gemcitabine plus doxorubicin in stage IIIB breast cancer: a preliminary report. Gomez, H., Kahatt, C., Falcon, S., et al.[2022]

The combination of carboplatin (CBDCA) and gemcitabine (GEM) is effective and safe for treating stage IV non-small-cell lung cancer (NSCLC), with a response rate of 35% in a study of 88 chemotherapy-naïve patients.

Administering CBDCA before GEM resulted in better patient outcomes, including a median survival of 13 months compared to 9 months for those receiving GEM first, highlighting the importance of treatment sequencing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical and clinical evaluation of four gemcitabine plus carboplatin schedules as front-line treatment for stage IV non-small-cell lung cancer. Bajetta, E., Stani, SC., De Candis, D., et al.[2022]

Combining gemcitabine with carboplatin has shown promising efficacy in treating advanced non-small-cell lung cancer, with recent studies indicating improved toxicity profiles compared to older regimens that used cisplatin.

New dosing schedules for gemcitabine, specifically administering it only on days 1 and 8 of a 21-day cycle, have reduced the risk of thrombocytopenia while maintaining effectiveness, making this combination a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in combination with new platinum compounds: an update. Gandara, DR., Edelman, MJ., Lara, PN., et al.[2022]

Gemcitabine has shown promising results as a single-agent treatment for platinum-resistant ovarian cancer, achieving remission rates of nearly 20% with a favorable safety profile.

Combining gemcitabine with carboplatin has been explored in phase I and II trials, showing potential for improved efficacy in treating ovarian cancer, and further combinations with other agents are being actively researched.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in ovarian cancer. Orlando, M., Mandachain, M.[2022]

References

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

A phase I trial of weekly gemcitabine and subcutaneous interferon alpha in patients with refractory renal cell carcinoma. [2022]

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

Integrating gemcitabine into breast cancer therapy. [2022]

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

Review of the pharmacoeconomic research on gemcitabine in the treatment of advanced non-small cell lung cancer. [2022]

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

Gemcitabine and UFT plus oral calcium folinate: phase I study. [2022]

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

Advances in treatment of inoperable NSCLC: gemcitabine doublets--a promising alternative. [2022]

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

A phase II study of neoadjuvant gemcitabine plus doxorubicin in stage IIIB breast cancer: a preliminary report. [2022]

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

Preclinical and clinical evaluation of four gemcitabine plus carboplatin schedules as front-line treatment for stage IV non-small-cell lung cancer. [2022]

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

Gemcitabine in combination with new platinum compounds: an update. [2022]

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

Gemcitabine in ovarian cancer. [2022]