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

AstraZeneca

Status and phase: Completed; Phase 1

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

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02658214

D419SC00001

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 32 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. ≥18 years
2. Written informed consent
3. 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.
4. ECOG performance status of 0 or 1
5. Patients must be considered suitable candidates for, and able to receive, first line chemotherapy for metastatic disease
6. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline
7. No prior exposure to immune-mediated therapy
8. Adequate organ and marrow function as defined below

Exclusion criteria

1. Receipt of any investigational anticancer therapy within 28 days or 5 halflives, whichever is longer, prior to the first dose of study treatment
2. 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
3. Any unresolved Grade ≥2 toxicity from previous anticancer therapy
4. Active or prior documented autoimmune or inflammatory disorders
5. 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
6. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms 20. Active tuberculosis
7. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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32 participants in 7 patient groups

Cohort 1

Experimental group

Description:

ovarian/peritoneal/fallopian tube cancer and squamous cell carcinoma of the head and neck (SCCHN)

Treatment:

Drug: paclitaxel + carboplatin

Biological: tremelimumab

Biological: durvalumab

Cohort 2

Experimental group

Description:

Small-cell lung cancer (SCLC)

Treatment:

Biological: tremelimumab

Drug: carboplatin + etoposide

Biological: durvalumab

Cohort 3

Experimental group

Description:

Triple-negative breast cancer (TNBC)

Treatment:

Biological: tremelimumab

Drug: gemcitabine + carboplatin

Biological: durvalumab

Cohort 4

Experimental group

Description:

Triple-negative breast cancer (TNBC)

Treatment:

Drug: nab-paclitaxel (paclitaxel-albumin) + carboplatin

Biological: tremelimumab

Biological: durvalumab

Cohort 5

Experimental group

Description:

Gastric/gastro-esophageal junction (GEJ)

Treatment:

Drug: oxaliplatin + 5-fluorouracil (5FU) + leucovorin (calcium folinate/folinic acid)

Biological: tremelimumab

Biological: durvalumab

Cohort 6

Experimental group

Description:

Pancreatic ductal adenocarcinoma (PDAC)

Treatment:

Biological: tremelimumab

Drug: nab-paclitaxel (paclitaxel-albumin) + gemcitabine

Biological: durvalumab

Cohort 7

Experimental group

Description:

Esophageal squamous cell carcinoma (ESCC)

Treatment:

Drug: cisplatin + 5-fluorouracil (5FU)

Biological: tremelimumab

Biological: durvalumab