Phase II Umbrella Study of Novel Anti-cancer Agents in Patients With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Drug: AZD6738 (ceralasertib)Drug: AZD6738 (ceralasertib) 7 days monotherapyDrug: AZD6738 (ceralasertib) (240 mg or 160 mg)
- Registration Number
- NCT03334617
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is an open-label, multi-centre, umbrella Phase II study in patients with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms.
- Detailed Description
This is an open-label, multi-centre, umbrella Phase II study in patients with metastatic non-small cell lung cancer (NSCLC) who have progressed on an anti-programmed cell death-1/anti-programmed cell death ligand 1 (anti-PD-1/PD-L1) containing therapy. This study is modular in design, consisting of a number of treatment cohorts, allowing evaluation of the efficacy, safety, and tolerability of multiple treatment arms. There is currently no established therapy for patients who have received immune checkpoint inhibitors and platinum-doublet therapies, and novel treatments are urgently needed.
This protocol has a modular design, with the potential for future treatment arms to be added via protocol amendment.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 527
Not provided
- Patients whose tumour samples have targetable alterations in EGFR and/or ALK at initial diagnosis are excluded. In addition, patients whose tumour samples are known to have targetable alterations in ROS1, BRAF, MET or RET, are to be excluded.
- Active or prior documented autoimmune or inflammatory disorders.
- Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).
- Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not willing to employ effective birth control.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients, or history of severe hypersensitivity reactions to other monoclonal antibodies.
- Patient has spinal cord compression or symptomatic brain metastases.
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Patients may receive treatment with bisphosphonates or receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitors for the treatment of bone metastases.
- history of active primary immunodeficiency
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description durvalumab + cediranib Durvalumab durvalumab given in combination with cediranib (AZD2171) Durvalumab + olaparib Durvalumab Durvalumab given in combination with olaparib . Durvalumab + olaparib Olaparib Durvalumab given in combination with olaparib . Durvalumab + vistusertib Durvalumab Durvalumab given in combination with Vistusertib (AZD2014). Durvalumab + AZD9150 AZD9150 Durvalumab given in combination with AZD9150. Durvalumab + AZD6738 Durvalumab Durvalumab given in combination with AZD6738. Durvalumab + vistusertib Vistusertib Durvalumab given in combination with Vistusertib (AZD2014). AZD6738 (ceralasertib) monotherapy AZD6738 (ceralasertib) AZD6738 (ceralasertib) given as monotherapy Durvalumab + AZD6738 AZD6738 Durvalumab given in combination with AZD6738. AZD6738 (ceralasertib) 7 days monotherapy AZD6738 (ceralasertib) 7 days monotherapy AZD6738 (ceralasertib) monotherapy on D1-7 of every 28 days durvalumab & AZD6738 (ceralasertib) AZD6738 (ceralasertib) durvalumab given in combination with AZD6738 (D15-D28) durvalumab & AZD6738 (ceralasertib) (240 mg or 160 mg) AZD6738 (ceralasertib) (240 mg or 160 mg) durvalumab in combination with twice daily 160 mg or 240 mg AZD6738 (D22-D28) Durvalumab + AZD9150 Durvalumab Durvalumab given in combination with AZD9150. Durvalumab + Oleclumab Durvalumab Durvalumab given in combination with Oleclumab durvalumab + trastuzumab deruxtecan trastuzumab deruxtecan durvalumab given in combination with trastuzumab deruxtecan (DS-8201a) durvalumab & AZD6738 (ceralasertib) Durvalumab durvalumab given in combination with AZD6738 (D15-D28) Durvalumab + Oleclumab Oleclumab Durvalumab given in combination with Oleclumab durvalumab + cediranib cediranib durvalumab given in combination with cediranib (AZD2171)
- Primary Outcome Measures
Name Time Method Assessment of the efficacy of each treatment by evaluation of objective response rate 12 weeks Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Objective response rate (ORR)
- Secondary Outcome Measures
Name Time Method Best percentage change in tumour size using RECIST 1.1 assessment for the anti-tumour activity of each therapy Through to study completion, up to 3.5 years. Assessment of the anti-tumour activity of each therapy.
Disease control rate (DCR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy. Through to study completion, up to 3.5 years. Assessment of the anti-tumour activity of each therapy.
Duration of response (DoR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy. Through to study completion, up to 3.5 years Assessment of the anti-tumour activity of each therapy.
Progression free survival (PFS) using RECIST 1.1 assessment for the anti-tumour activity of each therapy. Through to study completion, up to 3.5 years. Assessment of the anti-tumour activity of each therapy.
Overall surival (OS) Through to study completion, up to 4.5 years. Assessment of the anti-tumour activity of each therapy.
Trial Locations
- Locations (1)
Research Site
🇪🇸Sevilla, Spain