An experimental study to evaluate the safety and antitumor activity of avelumab in combination with talazoparib in patients with locally advanced or metastatic solid tumors.
- Conditions
- MedDRA version: 20.0Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864ocally advanced (primary or recurrent) or metastatic solid tumors, including non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), hormone receptor-positive (HR+) / human epidermal growth factor receptor 2-negative (HER2-) breast cancer, recurrent platinum-sensitive ovarian cancer, UC, and castration-resistant prostate cancer (CRPC).MedDRA version: 20.0Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001509-33-BE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 242
1. Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent (for more details refer to Protocol section 4.1).
2. Measurable disease by RECIST v1.1 with at least 1 measurable lesion; This criterion is not required for patients with metastatic CRPC.
3. Mandatory primary or metastatic tumor biopsy to be performed within 28 days (45 days for patients requiring prospective biomarker testing for eligibility evaluation) prior to study enrollment to allow FFPE tissue be submitted for protocol-required testing. Core needle or excision biopsies are required, as fine needle aspirations will not yield enough tissue for protocol-specified testing. If archival tumor tissue is available from a biopsy/surgery that was performed within 1 year prior to study enrollment and the patient did not receive any subsequent systemic anti-cancer treatment, the tumor tissue may be submitted without repeating a tumor biopsy during the screening period. For mCRPC patients with no biopsable lesion outside of bone, archival tumor tissue from a biopsy/surgery performed within 5 years prior to study enrollment must be submitted without repeating a tumor biopsy
during the screening period.
4. Age = 18 years (except in Japan, where patients must be = 20 years).
5. ECOG Performance Status 0 or 1.
6. Adequate Bone Marrow Function, including:
a. Absolute Neutrophil Count (ANC) =1,500/mm³ or =1.5 x 10?/L;
b. Platelets = 100,000/mm³ or =100 x 10? /L;
c. Hemoglobin =9 g/dL (=5.6 mmol/L).
7. Adequate renal function, defined by an estimated CrCl of =60 mL/min for patients enrolled in Phase 1b portion of the study and =30 mL/min for patients enrolled in Phase 2 portion of the study. CrCl should be estimated according to the Cockcroft-Gault formula.
8. Adequate Liver Function, including:
a. Total serum bilirubin =1.5;
b. AST and ALT =2.5 × ULN;
9. Female patients of childbearing potential must have negative serum pregnancy or urine pregnancy test at screening (see Protocol Section 7.1.1 for criteria to be considered not of childbearing potential).
Female patients of nonchildbearing potential must meet at least 1 of the following criteria:
? Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state;
? Have undergone a documented hysterectomy and/or bilateral oophorectomy;
? Have medically confirmed ovarian failure.
All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential.
10. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
11. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
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 this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 92
1. Prior treatment with a PARP inhibitor.
2. Prior immunotherapy with IL-2, IFN-a, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, OX-40, GITR, LAG-3, IDO, TDO, TIM-3, CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immunecheckpoint pathways. Prior treatment with Sipuleucel-T for patients with mCRPC is allowed. EXCEPTION for Cohort A2 only: Prior treatment with anti-PD-1/L1 therapy in the metastatic setting (Stage IV only) as described in Inclusion Criterion 1 is allowed.
3. Prior anti-cancer therapy within 2 weeks prior to study enrollment. Prior radiation therapy within 2 weeks prior to enrollment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed 2 days prior to study enrollment and no clinically significant toxicities are expected (eg, mucositis, esophagitis).
4. Major surgery within 4 weeks prior to study enrollment.
5. Current use of immunosuppressive medication at the time of study enrollment, EXCEPT for the following permitted steroids (see Protocol Section 5.7.5).
6. Known prior severe hypersensitivity to investigational products or any component in their formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade =3).
7. Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis.
8. Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypoor hyperthyroid disease not requiring immunosuppressive treatment are eligible.
9. Prior organ transplantation including allogenic stem-cell transplantation.
10. Vaccination within 4 weeks of study enrollment and while on trials is prohibited except for administration of inactivated vaccines.
11. Diagnosis of Myelodysplastic Syndrome (MDS).
12. Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable.
13. Participation in other studies involving investigational drug(s) within 4 weeks prior to study enrollment and/or during study participation.
14. Persisting toxicity related to prior therapy (NCI CTCAE v4.03 Grade >1); however alopecia and sensory neuropathy Grade =2, or other Grade =2 AEs not constituting a safety risk, based on Investigator's judgment, are acceptable.
15. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
16. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
17. Active infection requiring systemic therapy.
18. Clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (= New York Heart Association Classification Class II) or a serious cardiac arrhythmia requiring medication.
19. Current or anticipated use within 7 days prior to first dose of study drug, or anticipated use during the study of a strong P-gp
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method