non small-cell lung cancer
Conditions
Interventions
Durvalumab monotherapy:
- Durvalumab (1500 mg IV infusion) q4w
Placebo:
- Placebo (saline IV infusion) q4w.
Osimertinib monotherapy:
- Osimertinib (80 mg PO) QD
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Main cohort: 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 sample 8. Adequate organ and marrow function required 9. Patients with central or peripheral lesions are eligible 10. Staging must be done within 10 weeks before randomization (PET) 11. Pulmonary Function Testing within 12 weeks of randomization 12. Patients with a history of metachronus stage I/II (T1-T3N0M0) NSCLC treated definitely with surgery only or SBRT only > 1 yr prior to enrolment are eligible Osimertinib cohort: 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 sample 8. Adequate organ and marrow function required 9. Patients with central or peripheral lesions are eligible 10. Staging must be done within 10 weeks before randomization (PET) 11. Pulmonary Function Testing within 12 weeks of randomization 12. Patients with a history of metachronus stage I/II (T1-T3N0M0) NSCLC treated definitely with 13. Local confirmation of EGFR mutation (Ex19del and/or L858R)
Exclusion criteria
Exclusion criteria: Main cohort: 1. Mixed small cell and non-small cell cancer histology 2. History of allogeneic organ transplantation 3. History of another primary malignancy with exceptions 4. History of active primary immunodeficiency 5. Uncontrolled intercurrent illness (patients with controlled chronic obstructive pulmonary disease are allowed) 6. Known allergy or hypersensitivity to any of the drugs or any of the study drug excipients 7. Prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines 8. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. If patient has been on adjuvant hormonal treatment for early stage breast cancer for more than 5 years, and there is no evidence of recurrence, then patient is eligible with study physician discussion. 9. Major surgical procedure within 28 days prior to first dose of IP 10. Current or prior use of immunosuppressive medication within 14 days before the first dose of IP. 11. Positive pregnancy test for pre-menopausal women 12. local confirmation of EGFR mutation (Ex19del and/or L858R) Osimertinib cohort: 1. Mixed small cell and non-small cell cancer histology 2. Treatment with any of the following: - Preoperative (neoadjuvant) or adjuvant platinum-based or other chemotherapy for the disease under investigation; - Any prior anticancer or immunological therapy, including investigational therapy, for treatment of NSCLC for the disease under investigation; - Prior treatment with neoadjuvant or adjuvant EGFR-TKI; 3. History of another primary malignancy with exceptions 4. Sever or uncontrolled systemic disease. 5. Refractory nausea and vomiting, chronic GI diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib; 6. Any of the following cardiac criteria: - Mean resting QTc > 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine-derived QTcF value; - Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG - Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as electrolyte abnormalities 7. Past medical history of ILD, drug-induced ILD, or any evidence of clinically active ILD; 8. History of hypersensitivity to active or inactive excipients of osimertinib or drugs withva similar chemical structure or class to osimertinib;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - To assess the efficacy of durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of PFS in patients with subset of T1 to T3N0 NSCLC using BICR assessments according to RECIST 1.1 Osimertinib cohort: - To assess the efficacy of osimertinib following SoC SBRT in terms of 4-year PFS in patients with T1 to T3N0 NSCLC using BICR assessments according to RECIST 1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| - To assess the efficacy of durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of PFS in patients with T1 to T3N0 NSCLC using BICR assessments according to RECIST 1.1 - To assess the efficacy of durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of OS in patients with subset of T1 to T3N0 NSCLC and in patients with Stage I/II NSCLC - To further assess the efficacy of durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of PFS24, TTP, TTDM using BICR assessments according to RECIST 1.1, and PFS2 using local assessment - To assess the PK of durvalumab - To investigate the immunogenicity of durvalumab - To assess symptoms and health-related quality of life in patients treated with durvalumab with SoC SBRT compared to placebo with SoC SBRT using the EORTC QLQ-C30 Osimertinib cohort: - To assess the safety, tolerability, and compliance of a maximum of 3 years of osimertinib following SoC SBRT - To further assess other parameters of the efficacy of osimertinib following SoC SBRT - To assess the events following disease progression for these medically inoperable patients treated by osimertinib following SoC SBRT | — |
Countries
Netherlands
Outcome results
None listed