Phase 1 Trial of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Activity of RP-1664 in Participants with Advanced Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Repare Therapeutics USA Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Feb 2025 → 27 Aug 2025

Decision date (initial)

2024-07-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Repare Therapeutics

External identifiers

EU CT number

2024-511259-16-00

ClinicalTrials.gov

NCT06232408

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic

To assess the safety and tolerability of RP-1664 in participants with eligible, advanced solid tumors.
To define a dose and schedule of RP-1664 that is tolerated and has clinical activity.

Secondary objectives 2

1. To assess the PK parameters of RP-1664 in the fed and fasted states
2. To assess the preliminary anti-tumor activity of RP-1664 in participants with molecularly selected advanced solid tumors treated at pharmacologically active dose ranges.

Conditions and MedDRA coding

Advanced Solid Tumors

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 1. Written informed consent or assent, according to local guidelines, signed and dated by the participant or legal guardian prior to the performance of any trial-specific procedures, sampling, or analyses. Participants with impaired decision-making capacity must have a close caregiver or legally authorized representative (LAR) present.
2. 2. Male or female participants ≥ 18 years of age at the time of signing the informed consent.
3. 3. Ability to swallow and retain whole, intact oral medications.
4. 4. Life expectancy ≥ 4 months after the start of the treatment according to the Investigator’s judgment.
5. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or Lansky performance status ≥ 60%.
6. 6. Participant must have 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.
7. 7. Measurable disease per RECIST v1.1 or INRC.
8. 8. Provision of archival tumor tissue (if adequate archival tumor tissue is not available, tumor tissue should be acquired by a fresh biopsy prior to enrollment).
9. 9. All participants’ tumors must have evidence from a Clinical Laboratory Improvement Amendments (CLIA)‑certified or equivalent (ex-United States [US]) laboratory: Gain or amplification of TRIM37.
10. 10. Acceptable organ function at Screening.
11. 11. Acceptable hematologic function at Screening.
12. 12. Negative pregnancy test (serum) for women of childbearing potential (WOCBP) at Screening.
13. 13. Male participants with female partners of childbearing potential must follow a contraception method.
14. 14. For participants in the food effect portion of the trial, ability to consume a high-fat meal and fast for 12 hours.

Exclusion criteria 22

1. 1. History or current condition (such as transfusion-dependent anemia, thrombocytopenia) or laboratory abnormality that might pose a significant risk to participant safety, confound the trial results, or interfere with participation for the full duration of the trial treatment.
2. 10. Persistent Grade > 1 non-hematological toxicity from prior cancer therapy. Grade 2 peripheral neuropathy after documented treatment with taxanes and/or platinum-based therapy is allowed.
3. 11. Chemotherapy, small molecule or biologic antineoplastic agent given within 21 days or < 5 half‑lives.
4. 2. Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction, or other reasons which, in the Investigator’s opinion, could compromise the participant’s safety, or interfere with or compromise the integrity of the trial outcomes.
5. 3. Uncontrolled, symptomatic brain metastases.
6. 4. 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.
7. 5. Active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus, hepatitis C virus (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness.
8. 6. Clinically significant vascular (both arterial and venous) and non‑vascular cardiac conditions, active or within 6 months prior to enrollment.
9. 7. QT interval meeting protocol-specified criteria.
10. 8. Moderate or severe hepatic impairment (i.e., Child-Pugh class B or C).
11. 9. Uncontrolled hypertension.
12. 12. Other anticancer therapy while the participant is receiving trial intervention.
13. 13. 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.
14. 14. I-131 Meta-Iodo-Benzyl-Guanidine (MIGB) therapy within 6 weeks prior to initiation of trial treatment.
15. 15. Prior treatment with a PLK4 inhibitor.
16. 16. Use of radiotherapy (except for palliative reasons) within 14 days prior to trial treatment initiation.
17. 17. Current treatment with medications that are known to prolong the QT interval.
18. 18. Participants who are receiving strong P-glycoprotein (P-gp) inhibitors and/or breast cancer resistance protein (BCRP) inhibitors within 14 days prior to first dose of trial intervention.
19. 19. Major surgical procedures ≤ 28 days prior to trial treatment initiation.
20. 20. Gastrointestinal abnormalities, including inability to take whole, intact oral medication.
21. 21. Participants who are breastfeeding at screening or planning to become pregnant (self or partner) at any time during trial participation.
22. 22. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence and severity of treatment-emergent adverse events (TEAEs)
2. Dose and schedule based on safety, PK, pharmacodynamic, and available efficacy data

Secondary endpoints 2

1. Plasma concentrations of RP-1664 with calculation of maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), minimum observed plasma concentration (Cmin), area under the plasma concentration-time curve (AUC), elimination half life (t1/2), fraction excreted in urine (for food effect participants only) and other parameters as appropriate
2. Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or International Neuroblastoma Response Criteria (INRC; for participants with neuroblastoma). Overall response rate. Clinical benefit rate (CBR). Best percent change in tumor size from baseline. Progression-free survival (PFS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Repare Therapeutics USA Inc.

Sponsor organisation

Repare Therapeutics USA Inc.

Address

101 Main Street Suite 1650

City

Cambridge

Postcode

02142-1519

Country

United States

Scientific contact point

Organisation

Repare Therapeutics USA Inc.

Contact name

Gabriela Gomez, MD

Public contact point

Organisation

Repare Therapeutics USA Inc.

Contact name

Gabriela Gomez, MD

Third parties 4

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

4 submissions — initial application plus substantial / non-substantial modifications