Advanced Solid TumorPhase 1NCT06232408
LIONS (PLK4 Inhibitor in Advanced Solid Tumors)
A Phase 1 study testing RP-1664 in people with Advanced Solid Tumor, run by Repare Therapeutics at 5 sites in 2 countries.
Trial summary
The primary objective of this study is to identify a safe and tolerated dose and schedule of the orally administered PLK4 inhibitor RP-1664. In addition, this study will examine the pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of RP-1664 in advanced solid tumors. Read more about this study
- Who is it for?
- Ages 12 to 100 years
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- RP-1664
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 14 Feb 2024to 27 Aug 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Written informed consent or assent, according to local guidelines, signed and dated by the patient or legal guardian prior to the performance of any study-specific procedures, sampling, or analyses.
- Male or female and ≥ 12 years-of-age at the time of signature of the consent or assent, and are at least 6th grade reading level to consent; participants < 18 years of age must weigh at least 40 kg.
- Life expectancy ≥ 4 months.
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
- Locally advanced or metastatic solid tumor that has progressed or was nonresponsive or intolerant to available therapies and for which no standard or available curative therapy exists.
- Measurable disease as per RECIST v1.1 or INRC.
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- Existing biomarker profile (tumor tissue or plasma) reported from a local test obtained in a CLIA-certified or equivalent laboratory demonstrating eligible tumor biomarkers.
- Available tumor tissue.
- Molecularly eligible tumor profile from a CLIA-certified pathology report.
- Ability to comply with the protocol and study procedures detailed in the Schedule of Assessments.
- Ability to swallow and retain oral medications.
- Acceptable organ function at screening.
- Acceptable blood counts at screening.
- Negative pregnancy test (serum or urine) for females of childbearing potential at Screening and while on study drug.
- Resolution of all toxicities of prior treatment or surgery.
- Use of highly effective forms of contraception.
Who cannot join
- History or current condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment.
- Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction or other reasons which, in the investigator's opinion, could compromise the patient's safety.
- Uncontrolled, symptomatic brain metastases.
- Presence of other known second malignancy with the exception of any cancer that has been in complete remission for ≥ 2 years or completely resected squamous and basal cell carcinomas of the skin.
- Patients with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
- Clinically significant vascular (both arterial and venous) and non-vascular cardiac conditions, active or within 6 months prior to enrollment.
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- Moderate or severe hepatic impairment (ie, Child-Pugh class B or C).
- Uncontrolled high blood pressure.
- Chemotherapy, small molecule or biologic antineoplastic agent given within 21 days.
- Previously prescribed receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor initiated less than 4 months prior to trial entry. Bisphosphonates are allowed if initiated/administered at least 28 days prior to enrollment.
- I-131 Meta-Iodo-Benzyl-Guanidine (MIGB) therapy within 6 weeks prior to initiation of trial treatment.
- Prior treatment with a PLK4 inhibitor.
- Current treatment with medications that are known to prolong the QT interval.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Participating Site 1012
New Haven, Connecticut, 06519
Participating Site 1008
New York, New York, 10032
Participating Site 1004
New York, New York, 10065
Participating Site 1025
San Francisco, California, 94143
About this study
Official title: Phase 1 Trial of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Activity of RP-1664 in Participants With Advanced Solid Tumors
The primary objective of this study is to identify a safe and tolerated dose and schedule of the orally administered PLK4 inhibitor RP-1664. In addition, this study will examine the pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of RP-1664 in advanced solid tumors.
Read the detailed description
This is a first-in-human, Phase 1, multi-center, open-label, dose-escalation and expansion study to:
Evaluate the safety profile and MTD of RP-1664 and establish a recommended dose and schedule for further clinical investigation, In addition, the study aims to characterize the PK, PD, and preliminary anti-tumor activity of orally administered RP-1664. Exploratory objectives include examination of biomarker responses in relationship to RP-1664 exposure.
After the recommended dose and schedule is determined, expansion cohorts with molecularly selected advanced solid tumors will be enrolled to preliminarily assess the anti-tumor effect, and further examine the safety and PK of RP-1664 at the RP2D.
- Conditions
- Advanced Solid Tumor
- Being tested
- RP-1664
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP-1664Drug
RP-1664 will be supplied as immediate-release solid dosage form for oral self-administration.
| Study group | Role | What they receive |
|---|---|---|
| RP-1664 | Experimental | Not described Receives: Drug: RP-1664 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Related Treatment-Emergent Adverse Events (TRAE) With ≥3 CTCAE Grade
Number of participants with TRAE
Measured: Start of treatment through up to 6 months post last dose (up to 18 months)
Dose Limiting Toxicities (DLT) to Determine a Maximum Tolerated Dose and Schedule of RP-1664 Based on Safety and Tolerability
The number of participants with DLTs during the DLT observation period
Measured: During the first cycle (either 21 or 28 days) following the initiation of the study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2024
- Study start14 Feb 2024
- Primary completion27 Aug 2025
- Study completion27 Aug 2025
Why it stopped: Sponsor decided to terminate study early
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Repare Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06232408
- Sponsor's protocol ID
- RP-1664-01
- Status last verified
- Nov 2025
- First submitted
- 9 Jan 2024
- Last updated
- 21 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Vallee F, Casas-Selves M, Bubenik M, Duplessis M, Sow B, Suarez C, Sangiorgi B, Li L, Hyer M, Papp R, Leclaire ME, Perryman AL, Liu B, Surprenant S, Mochirian P, Pau V, Maderova Z, Mader P, Yin SY, Goodfellow E, Roulston A, Stocco R, Godbout C, Baruah P, Bonneau-Fortin A, Schonhoft JD, Nejad P, Norman D, Truong VL, Crane S, Attia MA, Mao D, Sicheri F, Marshall CG, Zimmermann M, Bendahan D, Gallant M, Black WC. Discovery of RP-1664: A First-in-Class Orally Bioavailable, Selective PLK4 Inhibitor. J Med Chem. 2025 Jun 12;68(11):10631-10647. doi: 10.1021/acs.jmedchem.5c00529. Epub 2025 May 16.
PubMed 40378279
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Trial of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Activity of RP-1664 in Participants With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT06232408
- Acronym / sponsor ID
- RP-1664-01
- Conditions
- Advanced Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decided to terminate study early
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Repare TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 14 Feb 2024 (actual)
- Primary completion
- 27 Aug 2025 (actual)
- Study completion
- 27 Aug 2025 (actual)
- First posted
- 30 Jan 2024 (actual)
- Results
- Posted 21 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to identify a safe and tolerated dose and schedule of the orally administered PLK4 inhibitor RP-1664. In addition, this study will examine the pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of RP-1664 in advanced solid tumors.
Detailed description
This is a first-in-human, Phase 1, multi-center, open-label, dose-escalation and expansion study to:
Evaluate the safety profile and MTD of RP-1664 and establish a recommended dose and schedule for further clinical investigation, In addition, the study aims to characterize the PK, PD, and preliminary anti-tumor activity of orally administered RP-1664. Exploratory objectives include examination of biomarker responses in relationship to RP-1664 exposure.
After the recommended dose and schedule is determined, expansion cohorts with molecularly selected advanced solid tumors will be enrolled to preliminarily assess the anti-tumor effect, and further examine the safety and PK of RP-1664 at the RP2D.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RP-1664 | Experimental | Drug: RP-1664 |
Who may qualify
- Ages
- 12 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- Written informed consent or assent, according to local guidelines, signed and dated by the patient or legal guardian prior to the performance of any study-specific procedures, sampling, or analyses.
- Male or female and ≥ 12 years-of-age at the time of signature of the consent or assent, and are at least 6th grade reading level to consent; participants < 18 years of age must weigh at least 40 kg.
- Life expectancy ≥ 4 months.
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
- Locally advanced or metastatic solid tumor that has progressed or was nonresponsive or intolerant to available therapies and for which no standard or available curative therapy exists.
Key exclusion criteria (13 listed)
- History or current condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment.
- Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction or other reasons which, in the investigator's opinion, could compromise the patient's safety.
- Uncontrolled, symptomatic brain metastases.
- Presence of other known second malignancy with the exception of any cancer that has been in complete remission for ≥ 2 years or completely resected squamous and basal cell carcinomas of the skin.
- Patients with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RP-1664RP-1664 will be supplied as immediate-release solid dosage form for oral self-administration. | Drug | RP-1664 |
Primary outcome
Treatment Related Treatment-Emergent Adverse Events (TRAE) With ≥3 CTCAE Grade
Time frame: Start of treatment through up to 6 months post last dose (up to 18 months)
Number of participants with TRAE
Dose Limiting Toxicities (DLT) to Determine a Maximum Tolerated Dose and Schedule of RP-1664 Based on Safety and Tolerability
Time frame: During the first cycle (either 21 or 28 days) following the initiation of the study treatment
The number of participants with DLTs during the DLT observation period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40378279Vallee F, Casas-Selves M, Bubenik M, Duplessis M, Sow B, Suarez C, Sangiorgi B, Li L, Hyer M, Papp R, Leclaire ME, Perryman AL, Liu B, Surprenant S, Mochirian P, Pau V, Maderova Z, Mader P, Yin SY, Goodfellow E, Roulston A, Stocco R, Godbout C, Baruah P, Bonneau-Fortin A, Schonhoft JD, Nejad P, Norman D, Truong VL, Crane S, Attia MA, Mao D, Sicheri F, Marshall CG, Zimmermann M, Bendahan D, Gallant M, Black WC. Discovery of RP-1664: A First-in-Class Orally Bioavailable, Selective PLK4 Inhibitor. J Med Chem. 2025 Jun 12;68(11):10631-10647. doi: 10.1021/acs.jmedchem.5c00529. Epub 2025 May 16.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RP-1664 in people with Advanced Solid Tumor, run by Repare Therapeutics at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Related Treatment-Emergent Adverse Events (TRAE) With ≥3 CTCAE Grade (time frame: Start of treatment through up to 6 months post last dose (up to 18 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06232408, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2025; AzTrials last refreshed its copy on 31 Oct 2026.