Health Condition 1: C348- Malignant neoplasm of overlappingsites of bronchus and lung
Conditions
Interventions
Intervention1: Durvalumab (MEDI4736): During the initial therapy phase, approximately 350 to 400 patients will receive treatment with durvalumab, along with the Investigator’s choice of platinum-based
Sponsors
AstraZeneca AB
Labcorp Drug Development India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF). Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, analyses and collection of sample for genetic analysis. 2. Female or male patients aged 18 years and above. 3. Histologically or cytologically documented Stage IV NSCLC not amenable to curative surgery or radiation. 4. Patients must have tumors that lack activating EGFR mutations and ALK fusions. - (WHO)/(ECOG) performance status of 0 or 1 - No prior chemotherapy or any other systemic therapy for Stage IV NSCLC - Adequate organ and marrow function without blood transfusions in the past 28 days, - At least 1 tumor lesion, not previously irradiated, that can be accurately measured as per RECIST 1.1. Key Inclusion criteria for randomization to maintenance treatment: 5. Documented radiographic evidence of CR, PR, or Stable Disease (SD) as per Investigator-assessed RECIST 1.1 following 4 cycles of platinum-based chemotherapy. 6. Creatinine Clearance (CrCl) 51 mL/min or more calculated by Cockcroft-Gault equation or measured by 24-hour urine collection. 7. Ability to swallow whole oral medications.
Exclusion criteria
Exclusion criteria: 1. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study. 2. Mixed small-cell lung cancer and sarcomatoid variant NSCLC histology. 3. Prior exposure to any chemotherapy agents (except chemotherapy or chemoradiation for non-metastatic disease), polyadenosine 5 diphosphoribose [poly (ADP ribose)] polymerase (PARP) therapy, or immunomediated therapy. 4. Active or prior documented autoimmune or inflammatory disorders. 5. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. 6. Current or prior use of immunosuppressive medication within 14 days before the first dose of Investigational Product (IP). 7. Untreated (CNS) metastases and/or carcinomatous meningitis. 8. Active infection. Exclusion criteria to be randomized to maintenance treatment: 9. Inability to complete 4 cycles of platinum-based chemotherapy for any reason or discontinuation of Durvalumab during initial therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the efficacy of durvalumab plus olaparib combination therapy compared with durvalumab monotherapy in terms of PFS (Investigator-assessed)Timepoint: PFS: Time from date of randomization until the date of objective radiological disease progression according to Investigator assessment using RECIST 1.1 or death (by any cause in the absence of progression) | — |
Secondary
| Measure | Time frame |
|---|---|
| To further assess the efficacy of durvalumab plus olaparib combination therapy compared with durvalumab monotherapy in terms of OS, ORR, and DoRTimepoint: OS: Time from date of randomization until the date of death by any cause ORR: Percentage of patients with an Investigator-assessed response of CR or PR after randomization DoR: Time from the date of first documented response following randomization until the first date of documented progression or death in the absence of disease progression;To assess disease-related symptoms and HRQoL in patients treated with durvalumab plus olaparib combination therapy compared with durvalumab monotherapyTimepoint: Change from baseline (for maintenance phase) in EORTC QLQ-C30 and EORTC QLQ-LC13 assessed on Day 1 and q4w thereafter. For subjects who discontinued study treatment, q4w since last dose up to 3 months post-treatment discontinuation. For subjects who discontinue study treatment due to toxicity (or symptomatic deterioration), assessment should be performed as follows: q4w for the first 3 months and q8w until 3 months post-RECIST 1.1-defined radiological PD;To assess the PK of durvalumab in combination with olaparibTimepoint: Concentration of durvalumab in PK sample of: - Initial therapy: Day 1, 22 and 64 - Maintenance phase (Durvalumab and Olaparib arm): Day 1, 29 and q12w thereafter - 3rd and 6th month since last dose for subjects who have discontinued study treatment;To further assess the efficacy of durvalumab plus olaparib combination therapy compared with durvalumab monotherapy in terms of PFS (Investigator-assessed) in the HRRm populationTimepoint: PFS: Time from date of randomization until the date of objective radiological disease progression according to Investigator assessment in HRRm population using RECIST 1.1 or death (by any cause in the absence of progression);To investigate the immunogenicity of durvalumabTimepoint: Presence of ADAs for durvalumab assessed at: - Initial therapy: Day 1, 22 and 6 | — |
Countries
Belgium, Hungary, India, Japan, Mexico, Netherlands, Poland, Republic of Korea, Romania, Russian Federation, Ukraine, United Kingdom, United States of America
Contacts
Public ContactShekhar Dawkhar
Labcorp Drug Development India Private Limited
Outcome results
None listed