Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors

A Phase I Multicenter Study of Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER)

This is an open-label, multicenter, phase I study to evaluate the safety and tolerability of durvalumab ± tremelimumab in combination with chemoradiation in patients with advanced solid tumors

This study will initially treat up to approximately 300 patients with advanced solid tumors at approximately 30 sites, worldwide. The study will be composed of a dose-limiting toxicity (DLT) assessment phase (Part A) and an expansion phase (Part B).

Inclusion criteria:

• World Health Organization (WHO)/ECOG performance status of 0 or 1
• Body weight >30 kg at enrollment and treatment assignment
• At least 1 measurable lesion, not previously irradiated
• No prior exposure to immune-mediated therapy (including therapeutic anticancer vaccines)
• For patients with oropharyngeal HNSCC HPV status has to be known

Exclusion criteria:

• Patients with simultaneous primary malignancies or bilateral tumors
• Active or prior documented autoimmune or inflammatory disorders
• Brain metastases or spinal cord compression
• Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV; positive HIV 1/2 antibodies)
• Has a paraneoplastic syndrome (PNS) of autoimmune nature
• HNSCC cohort: Head and neck cancer that does not include unresectable, locally advanced cancer of oral cavity, larynx, oropharynx or hypopharynx. HNSCC of unknown primary are also excluded
• NSCLC and SCLC cohort: Mixed SCLC and NSCLC histology
• SCLC cohort: Extensive-stage SCLC