A Phase II, Open-label, Multicenter, International Study of Durvalumab Following Radiation Therapy in Patients With Stage III, Unresectable Non-Small Cell Lung Cancer Who Are Ineligible for Chemotherapy
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- AstraZeneca
- Enrollment
- 102
- Locations
- 1
- Primary Endpoint
- Number of Patients With Grade 3 and Grade 4 Possibly-related Adverse Events (PRAEs)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase II open-label, single-arm, multicenter, international study to evaluate the clinical activity of durvalumab in patients with Stage III unresectable NSCLC who are deemed to be ineligible for chemotherapy per Investigator assessment. Patients will be enrolled into 2 cohorts according to radiotherapy pretreatment dose (Cohort A: standard radiation therapy [60 gray (Gy) ± 10% or hypofractionated bioequivalent dose (BED)]; Cohort B: palliative radiation therapy [40 to < 54 Gy or hypofractionated BED])
Detailed Description
This is a Phase II open-label, single-arm, multicenter, international study to evaluate the clinical activity of durvalumab in patients with Stage III unresectable NSCLC who have an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2 and who were treated with radiotherapy but are ineligible for chemotherapy. Patients will be enrolled into 2 cohorts according to the dose of radiotherapy received prior to study entry (Cohort A: Standard Radiotherapy \[60 Gy ± 10% or hypofractionated BED\]; Cohort B: Palliative Radiotherapy \[40 to \< 54 Gy or hypofractionated BED\]). Patients must not have progressed following radiation therapy, and radiation therapy must be completed within 6 weeks (42 days) prior to first study drug administration. The last dose of radiation therapy is defined as the day of the last radiation treatment session. All patients will receive 1500 mg durvalumab via IV infusion every 4 weeks (q4w) for up to a maximum of 12 months (up to 13 doses/cycles)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Capable of giving signed informed consent.
- •Age ≥ 18 years at study entry.
- •Histologically or cytologically documented NSCLC with locally-advanced, unresectable Stage III disease.
- •Deemed ineligible for chemotherapy per Investigator assessment.
- •Receipt of radiation therapy that was completed within 42 days prior to first study drug administration.
- •Must have received a total dose of radiation of 40 to 66 Gy (standard or hypofractionated BED).
- •Must not have progressed following radiation therapy, as per Investigator assessed RECIST 1.1 criteria: a) Patients with measurable disease and/or nonmeasurable and/or no evidence of disease assessed at baseline by computed tomography /magnetic resonance imaging will be eligible for this study. b) Prior irradiated lesions may be considered measurable and selected as target lesions (TLs) providing they fulfill the other criteria for measurability.
- •World Health Organization/ECOG performance status of ≤
- •No prior exposure to immune-mediated therapy including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1, and antiprogrammed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
- •Patients must have adequate organ and marrow function as defined below:
Exclusion Criteria
- •Patients with locally-advanced NSCLC whose disease has progressed following radiation therapy.
- •Mixed small cell lung cancer and NSCLC histology.
- •History of allogeneic organ transplantation.
- •Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome).
- •Uncontrolled intercurrent illness (e.g., ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris)
- •History of another primary malignancy except for (a) malignancy treated with curative intent and with no known active disease ≥ 5 years before the first study drug administration, (b) adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease, and c) treated carcinoma in situ without evidence of disease.
- •History of leptomeningeal carcinomatosis
- •History of active primary immunodeficiency
- •Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
- •Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia, and the laboratory values defined in the inclusion criteria
Arms & Interventions
Cohort A
Patients received standard radiotherapy \[60 gray (Gy) ± 10% or hypofractionated BED\] prior to study entry.
Intervention: Durvalumab
Cohort B
Patients received palliative radiotherapy \[40 to \< 54 Gy or hypofractionated BED\] prior to study entry.
Intervention: Durvalumab
Outcomes
Primary Outcomes
Number of Patients With Grade 3 and Grade 4 Possibly-related Adverse Events (PRAEs)
Time Frame: From first dose of durvalumab treatment until 6 months after initiation of durvalumab treatment
The safety and tolerability profile of durvalumab as defined by Grade 3 and Grade 4 PRAEs within 6 months from the initiation of durvalumab treatment. A PRAE was any TEAE with a possible relatedness to durvalumab, or where the relatedness was missing. If relatedness of a TEAE was missing at the primary DCO (30 March 2023) the TEAE was considered a PRAE.
Secondary Outcomes
- Median Progression-free Survival (mPFS)(From the first date of treatment until the date of objective disease progression or death or data cut-off date (36 months))
- Progression-free Survival at 6 Months (PFS6)(From the first date of treatment until the date of objective disease progression or death (6 months))
- Progression-free Survival at 12 Months (PFS12)(From the first date of treatment until the date of objective disease progression or death (12 months))
- Median Overall Survival (mOS)(From the first date of treatment until death or data cut-off due to any cause (36 months))
- Overall Survival at 12 Months (OS12)(From the first date of treatment until death due to any cause (12 months))
- Objective Response Rate (ORR)(From 8 weeks ±1 week after durvalumab treatment initiation and continue every 8 weeks (q8w) ±1 week through 48 weeks and every 12 weeks (q12w) ±1 week until disease progression or data cut-off (36 months))
- Duration of Response (DoR)(From 8 weeks ±1 week after durvalumab treatment initiation and continue every 8 weeks (q8w) ±1 week through 48 weeks and every 12 weeks (q12w) ±1 week until disease progression or data cut-off (36 months))
- Lung Cancer Mortality(From date of treatment start until death due to lung cancer (36 months))
- Number of Patients With Events (AEs)(From screening (Day -28) till data cut-off (36 months))
- Number of Patients With Adverse Events of Special Interests (AESIs)(From screening (Day -28) till data cut-off (36 months))
- Number of Patients With Immune-mediated Adverse Events (imAEs)(From screening (Day -28) till data cut-off (36 months))