A phase 1/2a trial to study how safe and tolerable RP-3500 is when administered along or in combination with talazoparib or gemcitabine in patients with certain types of cancer

Phase 1

• Conditions: Advanced/recurrent solid tumors which have ATRi sensitizing biomarkers; MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-000301-87-DK
• Lead Sponsor: Repare Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-08-11
• Last Update Posted: 29 July 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 451

Inclusion Criteria

Main criteria are the following ones (additional criteria can exist, depending on the module):
1. Written informed consent, 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.
2. Male or female and =18 years-of-age at the time of signature of the ICF.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
4. Histologically confirmed solid tumors resistant or refractory to standard treatment and/or patients who are intolerant to standard therapy.
5. Measurable disease as per RECIST v1.1
6. Existing biomarker profile reported from a local test obtained in a CAP/CLIA, ISO or equivalent laboratory per institutional guidelines
7. Provision of archival tumor tissue sample (or if adequate archival tumor tissue is not available, provision ofa fresh biopsy if there is a lesion that can be safelybiopsied).Note: If adequate archived tumor tissue is not available and/or a fresh biopsy cannot be safely performed, the patient may still be eligible with prior sponsor approval.
8. Ability to comply with the protocol and study procedures detailed in the Schedule of Assessments.
9. Ability to swallow and retain oral medications.
10. Acceptable organ function at Screening, as evidenced by the following laboratory data:
a. Serum creatinine =1.5 × upper limit of normal (ULN) or calculated creatinine clearance =60 mL/min using the Cockcroft-Gault equation or by 24-hour urine collection
b. Total bilirubin =1.5 × ULN or <3.0 × ULN if known Gilbert’s disease.
c. Serum albumin =2.5 g/dL
d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × ULN unless liver metastases are present and thought to be a reason for AST/ALT elevation, in which case they must be =5 × ULN
11. Acceptable hematologic function at Screening
a. No red blood cell or platelet transfusions or growth factors within 7 days of the first dose of RP-3500 for module 1 and within 14 days of first dose of study drug/s for modules 1 to 5.
b. Module 1: Hemoglobin =9.5 g/dL
Module 2 to 5: Hemoglobin =10 g/dL
c. ANC =1700 cells/mm3
d. Platelet count =140,000 cells/mm3
12. Negative pregnancy test for women of childbearing potential (WOCBP) at Screening (serum test only) and prior to the first dose of study drug.
13. Resolution of all toxicities of prior therapy or surgical procedures to baseline or Grade 1 (except for neuropathy, hypothyroidism requiring medication and alopecia which must have resolved to Grade =2). Any prior radiation (with exceptions for palliative radiotherapy) must have been completed at least 7 days prior to the start of study drugs, and patients must have recovered from any acute adverse effects prior to the start of study treatment.
14. Male patients with female partners of childbearing potential must follow a contraception method (oral contraceptives allowed) at least as conservative as Clinical Trial Facilitation Group (CTFG) recommendations during their participation in the study and for 6 months following last dose of study drug. Male patients must also refrain from donating sperm during their participation in the study and for 6 months following last dose of study drug.
15. Life expectancy =12 weeks after the start of the treatment according to the investigator's judgment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for thi

Exclusion Criteria

Main criteria are the following ones (additional criteria can exist, depending on the module):
1. Chemotherapy, small molecule anticancer or biologic anticancer therapy given within 14 days prior to first dose of study drug. For patients with breast or prostate cancer continuation of
long-term luteinizing hormone-releasing hormone (LHRH) or gonadotrophin releasing hormone (GnRH) are allowed if these medications were prescribed for at least 4 months before trial entry.
2. 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.
3. Prior therapy with an ATR or DNA-dependent protein kinase inhibitor.
4. Known hypersensitivity to any of the ingredients of RP-3500.
5. Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction (such as coagulopathy, encephalopathy or ascites requiring drainage within 4 weeks prior to enrollment) or other reasons which, in the investigator's opinion, could compromise the patient's safety, or interfere with or compromise the integrity of the study outcomes.
6. Uncontrolled, symptomatic brain metastases. Patients with previously treated brain metastases may participate provided the metastases are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study drug and any neurologic symptoms are controlled and stable), have no evidence of new or enlarging brain metastases, and are clinically stable off steroids for at least 7 days prior to study drug.
7. Uncontrolled hypertension (systolic blood pressure [BP] =160 mmHg; diastolic BP =100 mmHg) despite adequate treatment prior to first dose of RP-3500.
8. 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. In equivocal cases, patients whose viral load is negative, may be eligible. HIV seropositive patients who are healthy and low risk for AIDS related outcomes could be considered eligible. Eligibility criteria for HIV positive patients should be evaluated and discussed with Sponsor’s Medical Monitor, and will be based on current and past cluster of differentiation 4 (CD4) and t-cell counts, history (if any) of AIDS-defining conditions (eg, opportunistic infections), and status of HIV treatment.
9. Moderate or severe hepatic impairment (ie, Child-Pugh class B or C).
10. History or presence of an abnormal ECG that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or recent history of myocardial infarction that in the opinion of the Investigator will pose an increased risk of rhythm abnormalities.
11. QT interval corrected using Fridericia's formula (QTcF) >470 msec demonstrated by at least 2 ECGs >30 minutes apart.
12. History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (eg, severe left ventricular systolic dysfunction, left ventricular hypertrophy),
coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (eg, hypokalemia, hypomagnesemia, hypocalcemia), or family history of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified