Durvalumab and Tremelimumab in Combination With First-Line Chemotherapy in Advanced Solid Tumors

Study Overview
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Brief Summary
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Durvalumab and Tremelimumab in combination with first-line chemotherapy in the following indications: Ovarian/peritoneal/fallopian tube cancer, SCCHN, TNBC, SCLC and gastric/GEJ cancer, PDAC, ESCC.

Detailed Description
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7 cohorts of first-line chemotherapy regimens combined with durvalumab + tremelimumab. This study will evaluate the safety and tolerability of durvalumab (MEDI4736) + tremelimumab in combination with first line chemotherapy regimens in patients with locally advanced or metastatic solid tumors: ovarian/peritoneal/fallopian tube cancer, squamous cell carcinoma of the head and neck (SCCHN), triple negative breast cancer (TNBC), small cell lung carcinoma (SCLC), and gastric/gastro-esophageal junction (GEJ) cancer, pancreatic ductal adenocarcinoma (PDAC) and esophageal squamous cell carcinoma (ESCC).

Official Title
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A Phase Ib Study to Evaluate the Safety and Tolerability of Durvalumab and Tremelimumab in Combination With First-Line Chemotherapy in Patients With Advanced Solid Tumors.

Conditions
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Small Cell Lung Carcinoma, Carcinoma, Squamous Cell of Head and Neck, Stomach Neoplasms, Triple Negative Breast Neoplasms, Ovarian Neoplasms, Fallopian Tube Neoplasms, Peritoneal Neoplasms, Esophagogastric Junction Neoplasms, Carcinoma, Pancreatic Ductal, Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: paclitaxel + carboplatin
* Drug: carboplatin + etoposide
* Drug: gemcitabine + carboplatin
* Drug: nab-paclitaxel (paclitaxel-albumin) + carboplatin
* Drug: oxaliplatin + 5-fluorouracil (5FU) + leucovorin (calcium folinate/folinic acid)
* Biological: durvalumab
* Biological: tremelimumab
* Drug: nab-paclitaxel (paclitaxel-albumin) + gemcitabine
* Drug: cisplatin + 5-fluorouracil (5FU)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years Written informed consent Patients with histologically or cytologically documented chemotherapy-naïve locally advanced unresectable or metastatic ovarian/peritoneal/fallopian tube cancer, SCCHN, TNBC, SCLC, gastric cancer/GEJ, PDAC and ESCC. ECOG performance status of 0 or 1 Patients must be considered suitable candidates for, and able to receive, first line chemotherapy for metastatic disease At least 1 lesion, not previously irradiated, that can be accurately measured at baseline No prior exposure to immune-mediated therapy Adequate organ and marrow function as defined below Exclusion Criteria: Receipt of any investigational anticancer therapy within 28 days or 5 halflives, whichever is longer, prior to the first dose of study treatment Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment Any unresolved Grade ≥2 toxicity from previous anticancer therapy Active or prior documented autoimmune or inflammatory disorders Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from study drugs, or compromise the ability of the patient to give written informed consent Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms 20. Active tuberculosis Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>ovarian/peritoneal/fallopian tube cancer and squamous cell carcinoma of the head and neck (SCCHN) | Drug: paclitaxel + carboplatin<br>* IV infusion<br>* Other names: Platinum based Standard of Care Chemotherapy;Biological: durvalumab<br>* IV infusion<br>* Other names: MEDI4736;Biological: tremelimumab<br>* IV infusion<br>|
| Experimental: Cohort 2<br>Small-cell lung cancer (SCLC) | Drug: carboplatin + etoposide<br>* IV infusion<br>* Other names: Platinum based Standard of Care Chemotherapy;Biological: durvalumab<br>* IV infusion<br>* Other names: MEDI4736;Biological: tremelimumab<br>* IV infusion<br>|
| Experimental: Cohort 3<br>Triple-negative breast cancer (TNBC) | Drug: gemcitabine + carboplatin<br>* IV infusion<br>* Other names: Platinum based Standard of Care Chemotherapy;Biological: durvalumab<br>* IV infusion<br>* Other names: MEDI4736;Biological: tremelimumab<br>* IV infusion<br>|
| Experimental: Cohort 4<br>Triple-negative breast cancer (TNBC) | Drug: nab-paclitaxel (paclitaxel-albumin) + carboplatin<br>* IV infusion<br>* Other names: Platinum based Standard of Care Chemotherapy;Biological: durvalumab<br>* IV infusion<br>* Other names: MEDI4736;Biological: tremelimumab<br>* IV infusion<br>|
| Experimental: Cohort 5<br>Gastric/gastro-esophageal junction (GEJ) | Drug: oxaliplatin + 5-fluorouracil (5FU) + leucovorin (calcium folinate/folinic acid)<br>* IV infusion and bolus administration<br>* Other names: Platinum based Standard of Care Chemotherapy;Biological: durvalumab<br>* IV infusion<br>* Other names: MEDI4736;Biological: tremelimumab<br>* IV infusion<br>|
| Experimental: Cohort 6<br>Pancreatic ductal adenocarcinoma (PDAC) | Biological: durvalumab<br>* IV infusion<br>* Other names: MEDI4736;Biological: tremelimumab<br>* IV infusion<br>Drug: nab-paclitaxel (paclitaxel-albumin) + gemcitabine<br>* IV infusion<br>* Other names: Standard of Care Chemotherapy;|
| Experimental: Cohort 7<br>Esophageal squamous cell carcinoma (ESCC) | Biological: durvalumab<br>* IV infusion<br>* Other names: MEDI4736;Biological: tremelimumab<br>* IV infusion<br>Drug: cisplatin + 5-fluorouracil (5FU)<br>* IV infusion<br>* Other names: Platinum based Standard of Care Chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory findings (including: clinical chemistry, hematology, and urinalysis) | To assess the safety and tolerability profile of first-line chemotherapy in combination with durvalumab + tremelimumab | Throughout the study, approximately three years | 
| Incidence of Adverse Events | To assess incidence of Adverse Events for the safety and tolerability profile of first-line chemotherapy in combination with durvalumab and tremelimumab | Throughout the study, approximately three years | 
| Tumor assessment based on RECIST 1.1 (for cohort 6 only) | To estimate the objective response rate (ORR) of durvalumab + tremelimumab + chemotherapy (for cohort 6 only) | Throughout the study, approximately three years (for cohort 6 only) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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durvalumab, tremelimumab, metastatic, solid tumors, immuno-oncology, first-line chemotherapy, esophageal, pancreatic