LIONS (PLK4 Inhibitor in Advanced Solid Tumors)

NCT06232408 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: RP-1664-01
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 5

Brief 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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Treatment Related Treatment-Emergent Adverse Events (TRAE) With ≥3 CTCAE Grade

  Number of participants with TRAE

  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

  During the first cycle (either 21 or 28 days) following the initiation of the study treatment

Study Arms (1)

RP-1664

EXPERIMENTAL

Drug: RP-1664

Interventions

RP-1664 DRUG

RP-1664 will be supplied as immediate-release solid dosage form for oral self-administration.

RP-1664

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Repare Therapeutics: lead

Study Sites (5)

Participating Site 1025

San Francisco, California, 94143, United States

Location

Participating Site 1012

New Haven, Connecticut, 06519, United States

Location

Participating Site 1008

New York, New York, 10032, United States

Location

Participating Site 1004

New York, New York, 10065, United States

Location

Participating Site 4001

Copenhagen, Denmark

Location

Related Publications (1)

• 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.

  PMID: 40378279 DERIVED

Limitations and Caveats

The study was terminated early.

Results Point of Contact

• Title: Repare Therapeutics Medical Monitor
• Organization: Repare Therapeutics Inc

clininfo@reparerx.com

1 (857) 340-5402

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: January 30, 2024
• Study Start: February 14, 2024
• Primary Completion: August 27, 2025
• Study Completion: August 27, 2025
• Last Updated: November 21, 2025
• Results First Posted: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); DK (1)