Immunotherapy 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).

• Durvalumab (Drug), also known as MEDI4736: IV (intravenous)
• Tremelimumab (Drug): IV
• Cisplatin (dose level 4) (Drug): IV
• Cisplatin (dose level 3) (Drug): IV
• Carboplatin (dose level 1) (Drug): IV
• Carboplatin (dose level 2) (Drug): IV
• Etoposide (dose level 1) (Drug): IV
• Etoposide (dose level 2) (Drug): IV
• Paclitaxel (Drug): IV
• Pemetrexed (Drug): IV
• External beam radiation (dose level 1) (Radiation): radiation therapy
• External beam radiation (dose level 2) (Radiation): radiation therapy
• External beam radiation (hyperfractionated) (Radiation): radiation therapy
• Cisplatin (dose level 1) (Drug): IV
• Cisplatin (dose level 2) (Drug): IV
• External beam radiation (standard) (Radiation): radiation therapy

Primary outcomes

• Number of subjects with Dose Limiting Toxicities (DLTs) [From first dose of durvalumab until 28 days after completion of radiation therapy]
• Number of subjects with Adverse Events (AEs) [From first dose of durvalumab up to 90 days after the last dose of study treatment]

Secondary outcomes

• Progression-free survival (PFS) [From first dose until the date of objective disease progression or death, in the absence of progression at 12, 18 and 24 months, up to 4 years.]
• Overall Survival (OS) [From first dose until death due to any cause through study completion, up to 4 years]
• Objective response rate (ORR) [From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.]: Number (%) of patients with an overall response of complete response (CR) or partial response (PR).
• Best objective response (BoR) [From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.]: The best response based on the overall visit responses from each RECIST 1.1 assessment or the last evaluable assessment in the absence of RECIST 1.1 progression.
• Duration of response (DoR) [From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years.]: Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.
• Disease control rate (DCR) [From first dose until disease progression, at 18 weeks and 48 weeks.]
• Disease-free survival (DFS) [From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 years.]

Sex: All, ages: 18 Years to 110 Years

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

NIH grants: 2017