A Phase 1 interventional study of PLX038 + Tuvusertib in Solid Tumor, sponsored by Institut Curie. Terminated at 2 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-02.
Sponsored by Institut Curie · Phase 1, Interventional, and Treatment
Phase I with a dose finding cohort, followed by expansion cohorts in pre-specified tumor types.
This is an open label, multi-centric phase I with, first, a dose escalation step using an adaptation of the Bayesian Optimal INterval (BOIN) drug-combination, followed by 2 dose expansion cohorts using the Simon 2-stage design.
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.
starting combination level is c1 (PLX038 800mg/m2 and Tuvusertib 90mg). Groups of 3 patients will be sequentially enrolled. One week between the enrollment of the 1st patient and the 2 following patients is mandatory at a new combination level. The decision to (de)-escalate one of the two agents depends on the outcome of all patients treated at the current combination.
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.
3,517 studies on the registry are indexed under Neoplasm Metastasis; 885 are open to participants now.
This study's enrollment of 10 is below the median of 54 across 2,767 interventional studies indexed under Neoplasm Metastasis.
Browse Neoplasm Metastasis studies →Institut Curie is the lead sponsor of 134 studies on the registry; 28 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
Exclusion Criteria:
Dose expansion additional inclusion criteria
Breast cancer
ATM-mutated solid cancers
● Inactivating mutation of ATM (presence of truncating mutation or R337/R3008 missense mutation of ATM mono and/or biallelic, assessed by next-generation sequencing in a certified French genomics platform).
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
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.
Dose escalation step : Dose limiting toxicities (DLTs)
Dose limiting toxicities (DLTs) experienced during 21 days from the first IV infusion of PLX038 + Tuvusertib
Time frame: 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)
Time frame: 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.
Time frame: 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.
Time frame: Until 30 days after the last dose of IMP (44 months + 30 days)
Dose escalation step : Pharmacokinetics effect of PLX038 and Tuvusertib
Maximum Plasma Concentration effect of PLX038, SN38 and Tuvusertib
Time frame: through study completion, an average of 44 months
Dose escalation step : Pharmacodynamics effect of PLX038 and Tuvusertib
Maximum Plasma Concentration effect of PLX038, SN38 and Tuvusertib
Time frame: through study completion, an average of 44 months
Dose escalation step : objective response rate (ORR)
ORR defined as the percentage of patients with complete response (CR) or partial response (PR), as the best response measured at the disease assessmement after initiation of treament according to RECIST v1.1
Time frame: through study completion, an average of 44 months
Dose escalation step : Time to response (TTR)
TTR calculated from the initiation of treatment to best tumour response (CR/PR)
Time frame: through study completion, an average of 44 months
Dose escalation step : Duration of Response (DoR)
DoR defined as the time period from best tumour response to disease progression (according to RECIST v1.1)
Time frame: through study completion, an average of 44 months
Dose escalation step : Progression free survival (PFS)
PFS measured from the inclusion in the study to the first documented progression (according to RECIST v1.1) or death from any cause.
Time frame: through study completion, an average of 44 months
Expansion cohorts : Time to response (TTR)
TTR calculated from the initiation of treatment to best tumour response (CR/PR)
Time frame: through study completion, an average of 44 months
Expansion cohorts : Duration of Response (DoR)
DoR defined as the time period from best tumour response to disease progression
Time frame: through study completion, an average of 44 months
Expansion cohorts : Progression free survival (PFS)
PFS measured from the inclusion in the study to the first documented progression
Time frame: through study completion, an average of 44 months
Expansion cohorts : Overall Survival (OS)
OS is defined as the time from inclusion to the event death.
Time frame: through study completion, an average of 44 months
Expansion cohorts : Efficacy of PLX038 + Tuvusertib in pre-defined biomarker subgroups
Association between PLX038 + Tuvusertib efficacy and homologous recombination (HR) defect (assessed by HR genes mutational status and BCRAness phenotype), replication stress-related biomarkers such as SFLN11 expression, RB1 loss; genomic alterations in DDR genes
Time frame: through study completion, an average of 44 months
Expansion cohorts : Pharmacokinetics effect of PLX038 and Tuvusertib
Maximum Plasma Concentration effect of PLX038, SN38 and Tuvusertib
Time frame: through study completion, an average of 44 months
Expansion cohorts : Pharmacodynamics effect of PLX038 and Tuvusertib
Maximum Plasma Concentration effect of PLX038, SN38 and Tuvusertib
Time frame: through study completion, an average of 44 months
Exploratory endpoints
Association between PLX038 + Tuvusertib efficacy and quantitative changes of blood biomarkers (e.g. ctDNA) during therapy.
Time frame: through study completion, an average of 44 months
Plan to share: Yes — Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.
Supporting information: Study protocol, Sap
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