Informations générales (source: ClinicalTrials.gov)
A Phase I Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) With Dose Expansion Cohorts in Patients With Advanced Solid Tumors (POP-ART)
Interventional
Phase 1
Institut Curie (Voir sur ClinicalTrials)
janvier 2025
septembre 2029
05 avril 2025
Phase I with a dose finding cohort, followed by expansion cohorts in pre-specified tumor
types.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | François-Clément BIDARD | Contact (sur clinicalTrials) | |||
| CLCC RENE HUGUENIN INSTITUT CURIE | François-Clément BIDARD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- 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).
- 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).
- 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 who have had any major surgery within 28 days prior to inclusion.
- 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).
- Brain metastases, unless local therapy was completed and use of corticosteroids for
this indication discontinued for at least 3 weeks prior to inclusion. Signs or
symptoms of brain metastases must be stable for at least 28 days prior to inclusion.
No known progression of brain metastases (by imaging as assessed by RECIST version
1.1) can have occurred. Patients with leptomeningeal disease or meningeal
carcinomatosis are excluded.
- 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.
- Severe/uncontrolled intercurrent illness within the previous 28 days prior to
inclusion.
- 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.
Dose expansion additional inclusion criteria
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.
- Patients whose cancer has a CPS score ≥10 must have received prior pembrolizumab
unless (i) contra-indicated (ii) CPS score or pembrolizumab not available at time of
first line treatment start.
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).