RP-1664 for Cancer

No longer recruiting at 4 trial locations

Overseen By Joseph O'Connell, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Repare Therapeutics

Must not be taking: QT prolonging drugs

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine a safe and effective dose of RP-1664, a new oral treatment for advanced solid tumors. Researchers will study how the body processes the drug and its initial effects on tumors. The trial targets individuals whose solid tumors have not responded to available treatments and who possess specific tumor biomarkers (biological indicators of disease). Participants must be able to swallow pills and have no severe health conditions that could interfere with the trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, such as chemotherapy or biologic agents, at least 21 days before starting. Also, you cannot be on medications that prolong the QT interval (a heart rhythm measure).

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that RP-1664, a new cancer treatment, is promising in terms of safety. In studies, most patients, including those with advanced solid tumors, tolerated RP-1664 well and did not experience severe side effects.

The treatment targets a protein called PLK4, which aids cell division. By blocking this protein, RP-1664 can slow or stop cancer cell growth. While this is encouraging, the treatment is still being tested to determine the best dose and schedule.

Overall, early studies suggest that RP-1664 could be a safe and effective option for treating certain types of cancer. Prospective trial participants might find reassurance in these findings regarding the treatment's safety so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard cancer treatments like chemotherapy, radiation, or surgery, RP-1664 is unique because it targets cancer cells with a new mechanism of action. Researchers are excited about RP-1664 because it is designed to specifically attack cancer cells while sparing healthy ones, potentially reducing side effects. This precision targeting could lead to improved outcomes for patients and faster results compared to traditional therapies.

What evidence suggests that RP-1664 might be an effective treatment for cancer?

Research has shown that RP-1664, the investigational treatment in this trial, yields promising results. In animal studies, it significantly slowed tumor growth in certain cancer models and extended the animals' lifespans. It reduced tumor growth by over 80% in various lab and patient-derived models. Early human studies suggest that RP-1664 is safe and effective, showing signs of tumor reduction in specific cancer types. Overall, the evidence supports RP-1664's potential as an effective treatment for advanced solid tumors. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for men and women aged 12 or older with advanced solid tumors that have worsened after treatment, or didn't respond to previous therapies. They should be able to perform daily activities with ease or only slight difficulty (ECOG score of 0-1), have a life expectancy of at least 4 months, and must have measurable disease according to specific criteria. Participants under 18 must weigh at least 40 kg.

Inclusion Criteria

My organs are functioning well.

Use of highly effective forms of contraception

Ability to comply with the protocol and study procedures detailed in the Schedule of Assessments

Exclusion Criteria

Uncontrolled high blood pressure

I haven't had cancer treatment with drugs in the last 3 weeks.

I started RANKL inhibitor treatment less than 4 months ago. Bisphosphonates were started at least 28 days before joining.

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 RP-1664 to evaluate safety and determine the maximum tolerated dose (MTD)

8-12 weeks

Expansion Cohorts

Participants with molecularly selected advanced solid tumors receive RP-1664 at the recommended phase 2 dose (RP2D) to assess anti-tumor effect and further examine safety and pharmacokinetics

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RP-1664

Trial Overview The study is testing the safety and appropriate dose of RP-1664, an oral drug designed to inhibit PLK4, which may play a role in tumor cell growth. It will also look into how the body processes the drug (pharmacokinetics), how it affects the body (pharmacodynamics), and its preliminary effectiveness against tumors.

How Is the Trial Designed?

Group I: RP-1664 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Repare Therapeutics

Lead Sponsor

Trials

10

Recruited

1,300+

Citations

1. reparerx.com reparerx.com/wp-content/uploads/2025/10/B169-ANE_RP-1664_Poster_2025.pdf

Preliminary safety and antitumor activity of RP-1664, a first- ... These data support tolerability and efficacy of RP-1664 monotherapy among molecularly-selected and tumor-specific cohorts and support.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40766251/

The PLK4 inhibitor RP-1664 demonstrates potent single-agent ... RP-1664 showed robust anti-tumor activity in 14/15 neuroblastoma xenograft models and significantly extended survival in a transgenic murine ...

3. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/1734/758516/Abstract-1734-RP-1664-A-potent-and-selective-PLK4

Abstract 1734: RP-1664: A potent and selective PLK4 inhibitor ... In vivo, RP-1664 is highly efficacious, resulting in >80% tumor growth inhibition and sustained regressions in multiple cell and patient-derived ...

4. towardshealthcare.com towardshealthcare.com/news/repare-therapeutics-rp-1664-phase-1-trial

Repare Therapeutics RP-1664 Phase 1 Trial Results Repare Therapeutics shares encouraging safety, efficacy, and tolerability results from its Phase 1 LIONS trial of RP-1664, a first-in-class ...

5. ir.reparerx.com ir.reparerx.com/news-releases/news-release-details/repare-therapeutics-doses-first-patient-phase-1-clinical-trial-1

Repare Therapeutics Doses First Patient in Phase 1 ... “RP-1664 exhibited deep tumor growth inhibition and regressions in multiple TRIM37-high solid tumor and neuroblastoma xenograft models, both internally and in ...

6. reparerx.gcs-web.com reparerx.gcs-web.com/news-releases/news-release-details/repare-therapeutics-present-initial-data-phase-1-lions-clinical

Repare Therapeutics to Present Initial Data from Phase 1 ... Preclinical studies demonstrate that RP-1664 selectively inhibits PLK4 and drives potent synthetic lethality in TRIM37-high tumor models, both ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06232408

LIONS (PLK4 Inhibitor in Advanced Solid Tumors) In addition, this study will examine the pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of RP-1664 in advanced solid tumors.

8. reparerx.com reparerx.com/wp-content/uploads/2025/10/LB-C002-Abstract.pdf

LB-C002 Abstract Here we report the first-in-human safety and preliminary anti-tumor activity of RP-1664, a first-in- class, highly-selective PLK4 inhibitor, in patients ...