RP-6306 Combination Therapy for Cancer

Not currently recruiting at 9 trial locations

Overseen By Lesley Seymour

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Proton pump inhibitors

Disqualifiers: Other malignancies, Infections, Cardiac disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug, RP-6306, to determine its safety and effectiveness in treating certain types of advanced cancers alongside standard cancer treatments. Researchers aim to discover whether individuals with specific biomarkers (genetic indicators in the body) respond better to this treatment than those without these biomarkers. The trial includes different groups, each receiving RP-6306 combined with another treatment, such as Trastuzumab or Gemcitabine. Individuals with advanced cancers that have not responded to other treatments and possess specific genetic markers might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants, providing an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot take proton pump inhibitors, strong CYP3A inhibitors, or inducers during the trial. There is also a washout period (time without taking certain medications) required for previous chemotherapy or systemic therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that RP-6306 is promising in terms of safety when used with other drugs. Specifically, combining RP-6306 with RP-3500 proved safe and effective for patients with difficult-to-treat endometrial and ovarian cancers. Similarly, using RP-6306 with FOLFIRI was safe and led to positive results in gastrointestinal tumors with specific genetic changes.

When paired with gemcitabine, RP-6306 also demonstrated a good safety record in patients with advanced solid tumors. Earlier studies focused on patient tolerance of RP-6306, and the results were encouraging.

Overall, these findings suggest that RP-6306 is generally well-tolerated in different combinations and cancer types. However, it's important to remember that this treatment is still being tested, so unexpected side effects are possible. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the RP-6306 combination therapies for cancer because they offer a fresh approach compared to current options like chemotherapy or targeted therapies alone. RP-6306, when combined with agents like RP-3500, Trastuzumab, Gemcitabine, or FOLFIRI, targets cancer cells more precisely by focusing on specific molecular pathways. This could lead to improved effectiveness and reduced side effects, as the treatment aims to selectively attack cancer cells while sparing healthy ones. Moreover, these combinations are designed to enhance the body's response to cancer treatment, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for cancer?

This trial will evaluate the effectiveness of RP-6306 combined with various cancer therapies. Research has shown that combining RP-6306 with RP-3500, one of the trial's treatment arms, may help treat certain cancers. In studies, this combination led to moderate tumor shrinkage and partial responses, with about 48.1% of patients experiencing clinical benefits.

Another treatment arm combines RP-6306 with Trastuzumab. Previous studies have shown that Trastuzumab reduces the risk of cancer progression or death when used with chemotherapy, suggesting possible benefits when combined with RP-6306.

The trial also includes a treatment arm combining RP-6306 with Gemcitabine. This pairing has demonstrated increased effectiveness against tumors, successfully stopping cancer growth in lab and animal studies, and working better together than alone.

Finally, the combination of RP-6306 with FOLFIRI is another treatment arm in this trial. It showed a positive response in 18.2% of patients with gastrointestinal tumors who had undergone extensive previous treatments. In some cases, significant tumor shrinkage and molecular changes occurred, suggesting potential benefits in cancer treatment. ^{1 2 3 6 7}

Who Is on the Research Team?

Stephanie Lheureux

Principal Investigator

University Health Network, Princess Margaret Hospital, Toronto ON Canada

Yvette Drew

Principal Investigator

BCCA-Vancouver Cancer Centre, Vancouver BC Canada

Eric Chen

Principal Investigator

University Health Network, Princess Margaret Hospital, Toronto ON Canada

Are You a Good Fit for This Trial?

Adults with advanced cancers like endometrial, NSCLC, ovarian carcinosarcoma, TNBC, PDAC, colorectal cancer or HER-2+ gastroesophageal cancer. They must have tried some treatments already (like platinum-based chemotherapy), be in good physical condition and expected to live at least 3 months. Specific genetic markers are required for some cohorts. Pregnant women and those with certain health conditions or previous hypersensitivity to study drugs can't join.

Inclusion Criteria

I have never been treated with gemcitabine.

Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to screening (if applicable)/enrollment in the trial to document their willingness to participate

My cancer has a TP53 mutation.

Exclusion Criteria

Patients are not eligible if they have a known hypersensitivity to the study drug(s) or their components

Pregnant or breastfeeding women

I cannot stop taking my proton pump inhibitors or certain other medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RP-6306 in combination with standard treatments such as Trastuzumab, RP-3500, Gemcitabine, or FOLFIRI

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RP-6306

Trial Overview The trial is testing RP-6306's safety and effectiveness against various advanced cancers when combined with standard treatments such as Gemcitabine or FOLFIRI Protocol. It also examines if patients' biomarkers affect their response to the treatment compared to usual cancer care approaches.

How Is the Trial Designed?

Group I: RP-6306 + RP-3500 Active Control 2 Interventions

Group II: RP-6306 + Trastuzumab Active Control 2 Interventions

Group III: RP-6306 + Gemcitabine Active Control 2 Interventions

Group IV: RP-6306 + FOLFIRI Active Control 2 Interventions

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Repare Therapeutics

Industry Sponsor

Trials

10

Recruited

1,300+

Published Research Related to This Trial

In a study involving 43 patients with castrate-resistant prostate cancer (CRPC), the combination of docetaxel, bevacizumab, and everolimus showed significant anticancer activity, with 79% of patients achieving a prostate-specific antigen decline of ≥30%.

While the combination therapy was found to be safe, with manageable toxicities, it did not demonstrate improved outcomes compared to docetaxel alone, highlighting the need to weigh potential benefits against the risk of increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Docetaxel, Bevacizumab, and Everolimus for Castration-resistant Prostate Cancer (CRPC). Gross, ME., Dorff, TB., Quinn, DI., et al.[2020]

Palomid 529 (P529), a TORC1/TORC2 inhibitor, effectively reduces cell proliferation and induces apoptosis in hormone-refractory prostate cancer (HRPC) cells, especially in those lacking the PTEN gene, indicating its potential as a targeted therapy.

Combining P529 with conventional chemotherapy drugs like docetaxel and cisplatin shows strong synergistic effects, leading to increased complete responses and reduced tumor progression in in vivo models, suggesting a promising new treatment strategy for HRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate cancer cells. Gravina, GL., Marampon, F., Petini, F., et al.[2022]

mTOR is a key protein involved in cancer development, making it a promising target for cancer therapies, particularly through the use of mTOR inhibitors like everolimus and temsirolimus, which are already approved for certain cancers.

Both first-generation (rapalogs) and second-generation mTOR inhibitors are being actively researched in clinical trials to determine their effectiveness against various cancers, with ongoing studies focusing on optimal treatment strategies and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mTOR signaling and drug development in cancer. Dancey, J.[2021]

The novel allosteric Akt inhibitor MK-2206 has shown promising results in enhancing the effectiveness of various anticancer agents, including both targeted therapies like erlotinib and cytotoxic drugs such as doxorubicin, in human cancer cell lines.

In vivo studies demonstrated that MK-2206 significantly increased tumor inhibition when used in combination with these agents, suggesting it could be a valuable addition to cancer treatment regimens, particularly for tumors resistant to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Hirai, H., Sootome, H., Nakatsuru, Y., et al.[2022]

The maximum tolerated dose (MTD) of MK-2206 was determined to be 45 mg every other day or 200 mg every three weeks, with common side effects including fatigue, nausea, and skin rash.

In this phase 1 study involving 72 patients with advanced solid tumors, MK-2206 showed promising antitumor activity when combined with chemotherapy and targeted therapies, with some patients experiencing complete or partial responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. Molife, LR., Yan, L., Vitfell-Rasmussen, J., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05147350

Study of RP-6306 With FOLFIRI in Advanced Solid Tumors Study Overview. The primary purpose of this study is to assess the safety and tolerability of RP-6306 with FOLFIRI in patients with eligible advanced solid ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12263950/

Targeted delivery of the PKMYT1 inhibitor RP-6306 ... RP-6306 effectively inhibits PDAC growth in vitro and in vivo, and shows enhanced anti-tumor activity when combined with gemcitabine, also ...

3. ir.reparerx.com ir.reparerx.com/news-releases/news-release-details/repare-therapeutics-announces-positive-initial-data-esmo-gi

Repare Therapeutics Announces Positive Initial Data at ... Overall response of 18.2% in heavily pretreated patients across gastrointestinal tumors with target alterations regardless of prior ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/50/NCT05147350/SAP_001.pdf

Statistical Analysis Plan Study Code RP-6306-03 ... ... RP-6306 (Module 1a) and, if necessary, intermittent RP-6306 (Module 1b) in combination with FOLFIRI. The target toxicity rate is. 25%. DLTs ...

5. onclive.com onclive.com/view/lunresertib-plus-folfiri-shows-safety-elicits-responses-in-ccne1-or-fbxw7-advanced-gi-tumors

Lunresertib Plus FOLFIRI Shows Safety, Elicits Responses ... This patient achieved a PR at 6 weeks, a best target lesion decrease from baseline of –65.2%, and a molecular response at 4 weeks of –98%.

6. clinicaltrials.eu clinicaltrials.eu/inn/rp-6306/

RP-6306: A Promising New Drug for Advanced Cancers RP-6306 is an investigational drug currently being studied in clinical trials for the treatment of various advanced solid tumors.

7. ctv.veeva.com ctv.veeva.com/study/study-of-rp-6306-with-folfiri-in-advanced-solid-tumors

Study of RP-6306 With FOLFIRI in Advanced Solid Tumors The primary purpose of this study is to assess the safety and tolerability of RP-6306 with FOLFIRI in patients with eligible advanced solid ...