A Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) in Patients With Advanced Solid Tumors

NCT06337630 | Terminated Phase 1

• 1 other identifier: IC 2022-10
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

Phase I with a dose finding cohort, followed by expansion cohorts in pre-specified tumor types.

Conditions

Solid Tumor

Keywords

Pretreated; Metastatic; Locally; Advanced triple negative breast; ATM Gene Mutation

Outcome Measures

Primary Outcomes (4)

• Dose escalation step : Dose limiting toxicities (DLTs)

  Dose limiting toxicities (DLTs) experienced during 21 days from the first IV infusion of PLX038 + Tuvusertib

  21 days

• Expansion cohorts : Best tumor response

  Best tumor response (defined as PR or CR in the first 6 months of treatment, assessed by investigators per RECIST v1.1 criteria)

  6 months

• Expansion cohorts : Serious Adverse Events (SAEs)

  Serious Adverse Events (SAEs) according to NCI CTCAE v5.0 by grade and their relationship to PLX038 + Tuvusertib.

  Until 30 days after the last dose of IMP (44 months + 30 days)

• Expansion cohorts : Adverse Events (AEs)

  Adverse Events (AEs) according to NCI CTCAE v5.0 by grade and their relationship to PLX038 + Tuvusertib.

  Until 30 days after the last dose of IMP (44 months + 30 days)

Secondary Outcomes (14)

• Dose escalation step : Pharmacokinetics effect of PLX038 and Tuvusertib

  through study completion, an average of 44 months

• Dose escalation step : Pharmacodynamics effect of PLX038 and Tuvusertib

  through study completion, an average of 44 months

• Dose escalation step : objective response rate (ORR)

  through study completion, an average of 44 months

• Dose escalation step : Time to response (TTR)

  through study completion, an average of 44 months

• Dose escalation step : Duration of Response (DoR)

  through study completion, an average of 44 months

Study Arms (1)

Single arm: treatment with PLX038 and Tuvusertib

EXPERIMENTAL

Dose escalation step Dose escalation will be conducted on the grid defined by the 4 doses of PLX038 (800 mg/m², 1000 mg/m², 1300 mg/m² and 1700 mg/m² IV every 21 days D1=D22) and 3 doses of Tuvusertib (90 mg, 130 mg and 180 mg QD for 10 days from D3, D3-12). Premedication with anti-emetic agents is not required prior to the initial infusion, but may be used for an individual patient, as needed. Expansion cohorts Two expansion cohorts are planned, investigating the efficacy and safety in pre-specified populations of interest. Patients will be treated at the RP2D; 25 evaluable patients are needed in each cohort, to account for possible non evaluable patients, up to 28 patients will be enrolled in each cohort. Patients enrolled in the phase I part at the RP2D and fulfilling the eligibility criteria of one of the expansion cohorts will be counted in those 25 evaluable patients.

Drug: PLX038 + Tuvusertib

Interventions

PLX038 + Tuvusertib DRUG

Dose escalation will be conducted on the grid defined by the 4 doses of PLX038 (800 mg/m², 1000 mg/m², 1300 mg/m² and 1700 mg/m² IV every 21 days D1=D22) and 3 doses of Tuvusertib (90 mg, 130 mg and 180 mg QD for 10 days from D3, D3-12). Premedication with anti-emetic agents is not required prior to the initial infusion, but may be used for an individual patient, as needed. All included patients will receive PLX038 + Tuvusertib until progression of disease, unacceptable toxicity, patient withdrawal of consent, investigator decision, lost to follow-up, death, patient non-compliance, or study termination by Sponsor.

Single arm: treatment with PLX038 and Tuvusertib

Eligibility Criteria

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

You may qualify if:

• Willing and able to comply with the protocol and provide written informed consent prior to study-specific screening procedures.
• Age ≥ 18 years.
• Locally advanced or metastatic solid cancer that is not amenable to curative treatment.
• Measurable disease (per RECIST version 1.1).
• Received a minimum of one and a maximum of six prior cytotoxic chemotherapy regimens for locally advanced or metastatic cancer.
• Resolution of chemotherapy and radiation therapy related toxicities to NCI-CTCAE version 5.0 Grade 1 or lower severity, except for stable sensory neuropathy (≤ Grade 2), alopecia (any grade), presence of clinically managed chronic autoimmune AEs from prior immune therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function (obtained within 14 days prior to treatment start) as evidenced by:
• i. Absolute neutrophil count (ANC) ≥ 1.5 X 109/L; ii. Hemoglobin (Hgb) ≥ 9 g/dL; iii. Platelet count ≥ 100 X 109/L; iv. Bilirubin ≤ 1.5 X upper limit of normal (ULN), except for patients with a documented history of Gilbert's disease (≤ 2 X ULN); v. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 2.5 X ULN (for patients with liver metastases ≤ 5 X ULN); vi. Alkaline phosphatase (ALP) ≤ 3 X ULN (for patients with liver metastases, ≤ 5 X ULN); vii. Serum creatinine ≤ 1.5 mg/dL (133 μmol/L) or calculated creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula); viii. Women of childbearing potential (WCBP): negative serum pregnancy test.
• Full blood count parameters described above must meet the thresholds with no transfusion or growth factor support in the past 14 days.
• Patients covered by social security or health insurance in compliance with the national legislation relating to biomedical research.
• The willingness to remain on contraception of childbearing potential for the duration of study treatment plus 7 months (women) or 4 months (men).

You may not qualify if:

• Patients who have had a last dose of IV chemotherapy within 21 days, last dose of oral cytotoxic chemotherapy, radiotherapy, biological therapy, or investigational therapy within 14 days prior to treatment start.
• Patients with chronic inflammatory bowel disease and/or bowel obstruction.
• Concomitant use of other agents for the treatment of cancer (except for LHRH agonist/antagonist) or any investigational agent(s).
• Women who are either pregnant, lactating, planning to get pregnant.
• Patients receiving pharmacotherapy for hepatitis B or C, tuberculosis, or HIV.
• Patients with known liver disease diagnosed with Child-Pugh A or higher cirrhosis.
• Other current or previous stage III or IV malignancy diagnosed within 5 years of study entry.
• Uncontrolled or poorly controlled arterial hypertension, symptomatic congestive heart failure (New York Heart Association Classification ≥ Class III), uncontrolled cardiac arrhythmia, calculated QTc average using the QTcF \> 480 msec; unstable angina pectoris, myocardial infarction or a coronary revascularization procedure, cerebral vascular accident, transient ischemic attack, or any other significant vascular disease within 180 days of study intervention start.
• Patients with ongoing active infection (requiring systemic treatment) and treatment with live or live attenuated vaccine within 30 days of dosing.
• Any other significant medical, psychological, social or geographic conditions that in the opinion of the Investigator would impair study participation or cooperation.
• Patients deprived of their liberty or under guardianship.
• Breast cancer
• Triple-negative breast cancer (both ER and PR \<10%, HER2-negative or HER2-low, locally assessed).
• Prior therapy (administered in the neoadjuvant, adjuvant and/or metastatic setting) with an anthracycline, taxane and sacituzumab govitecan (unless not medically appropriate or contraindicated for the patient).
• Patients with known gBRCA mutations must have received a PARP inhibitor in the metastatic setting.

Sponsors & Collaborators

• Institut Curie: lead
• ProLynx LLC: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Institut Curie

Paris, 75005, France

Location

Institut Curie

Saint-Cloud, 92210, France

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Model Details: Phase I with a dose finding cohort, followed by expansion cohorts in pre-specified tumor types.

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: March 29, 2024
• Study Start: January 20, 2025
• Primary Completion: November 24, 2025
• Study Completion: November 24, 2025
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR (2)