This is a Phase III, randomized, placebo-controlled, double-blind, multi-center study assessing the efficacy and safety of durvalumab with SoC SBRT versus placebo with SoC SBRT in patients with unresected clinical Stage I/II lymph node-negative (T1 to T3N0M0) NSCLC.
Recruiting
Phase 3
| Drug | Synonyms | Arms |
|---|---|---|
| Durvalumab | MEDI4736 | SoC SBRT + Durvalumab Therapy |
Patients who are to receive SoC SBRT as definitive treatment of stage I-II lymph node-negative NSCLC and confirmed to meet all eligibility criteria will be randomized 1:1 to durvalumab or placebo. The primary objective of this study is to assess the efficacy of durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of PFS. Key secondary is to assess the efficacy of Durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of OS.
| Name | Type | Description | Interventions |
|---|---|---|---|
| SoC SBRT + Durvalumab Therapy | Experimental | SBRT - delivered in 3, 4, 5 or 8 fractions. Durvalumab (PD-L1 monoclonal antibody) 1500 mg every 4 weeks [q4w] intravenously [iv] for up to 24 months or until progression or other discontinuation criteria are met. |
|
| SoC SBRT + Placebo Therapy | Placebo Comparator | SBRT - delivered in 3, 4, 5 or 8 fractions. Placebo (matching placebo for infusion every 4 weeks iv for up to 24 months or until progression or other discontinuation criteria are met. |
Key Inclusion Criteria:
1. Age ≥18 years
2. Histologically or cytologically documented Stage I to II NSCLC, with clinical Stage
I/II lymph node-negative (T1 to T3N0M0) disease and planned to receive definitive
treatment with SBRT. Patients may be medically inoperable or are medically operable
and refusing surgery or choosing to have SBRT (Stereotactic Body Radiation Therapy) as
definitive therapy
3. Planned SoC SBRT as definitive treatment
4. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) PS of 0, 1,
or 2
5. Life expectancy of at least 12 weeks
6. Body weight >30 kg
7. Submission of available tumor tissue sample
8. Adequate organ and marrow function required
9. Patients with central or peripheral lesions are eligible
10. Staging studies must be done within 10 weeks before randomization
11. Patients with a history of metachronus stage I/II (T1-T3N0M0) NSCLC treated
definitively surgery only or SBRT only >1 year prior to enrollment are eligible.
Key Exclusion Criteria:
1. Mixed small cell and non-small cell cancer
2. History of allogeneic organ transplantation
3. History of another primary malignancy with exceptions
4. History of active primary immunodeficiency
| Maximum Eligible Age: | 130 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Progression-Free Survival (PFS) assessed by BICR according to RECIST 1.1 in subpopulation of patients with Stage I/II NSCLC |
| Time Frame: | up to 6 years |
| Safety Issue: | |
| Description: |
| Measure: | Progression-Free Survival (PFS) assessed by BICR per RECIST 1.1 in all randomised patients with Stage I/II NSCLC |
| Time Frame: | up to 6 years |
| Safety Issue: | |
| Description: |
| Measure: | Overall Survival (OS) |
| Time Frame: | up to 7 years |
| Safety Issue: | |
| Description: |
| Measure: | Lung cancer-specific mortality |
| Time Frame: | up to 7 years |
| Safety Issue: | |
| Description: |
| Measure: | Peak Plasma Concentration (Cmax) |
| Time Frame: | up to 27 months |
| Safety Issue: | |
| Description: |
| Measure: | Detection of ADA neutralising antibodies titers |
| Time Frame: | up to 30 months |
| Safety Issue: | |
| Description: |
| Measure: | Health-related quality of life in patients treated with durvalumab with SoC SBRT compared to placebo with SoC SBRT using the EORTC QLQ-C30 |
| Time Frame: | up to 7 years |
| Safety Issue: | |
| Description: |
| Measure: | Proportion of patients alive and progression free at 24 months from randomisation (PFS24) assessed by BICR according to RECIST 1.1 |
| Time Frame: | at 24 months following randomization |
| Safety Issue: | |
| Description: |
| Measure: | Time to progression (TTP) assessed by BICR according to RECIST 1.1 |
| Time Frame: | up to 6 years |
| Safety Issue: | |
| Description: |
| Measure: | Time to death or distant metastasis (TTDM) assessed by BICR according to RECIST 1.1 |
| Time Frame: | up to 6 years |
| Safety Issue: | |
| Description: |
| Measure: | Time from randomisation to second progression (PFS2) as defined by local standard clinical practice |
| Time Frame: | up to 7 years |
| Safety Issue: | |
| Description: |
| Measure: | Trough Concentration (Ctrough) |
| Time Frame: | up to 27 months |
| Safety Issue: | |
| Description: |
| Measure: | Assessment of AEs by CTCAE v 5.0 as measures of the safety and tolerability of durvalumab with SoC SBRT compared to placebo with SoC SBRT |
| Time Frame: | up to 27 months |
| Safety Issue: | |
| Description: |
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | AstraZeneca |
April 19, 2021
