Durvalumab and Tremelimumab in Combination With Chemotherapy in HIV-infected Patients With Non-small Cell Lung Cancer

NCT04499053 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00002036
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

This is a phase II trial of durvalumab and tremelimumab in combination of platinum-based chemotherapy. Patients with stage IV Non-Small-Cell-Lung Cancer (NSCLC) with human immunodeficiency virus (HIV) infection will be eligible. Patients will receive standard platinum-based chemotherapy plus durvalumab for 4 cycles (every 3 weeks), followed by durvalumab (with or without pemetrexed for non-squamous NSCLC) maintenance therapy. It is hypothesized that Durvalumab and tremelimumab in combination with standard chemotherapy is safe and effective for the treatment of stage IV NSCLC in patients with HIV infection.

Conditions

Carcinoma, Non-Small Cell Lung

Keywords

Lung Cancer; Non-Small Cell Lung Cancer; Durvalumab; Tremelimumab

Outcome Measures

Primary Outcomes (2)

• Adverse Events

  Incidence of treatment-emergent Adverse Events according to NCI CTCAE v5.0.

  At the end of Cycle 4 (each cycle is 3 weeks)

• Radiological Response

  Radiological response will be evaluated using Recist Version 1.1 Criteria

  At the end of Cycle 4 (each cycle is 3 weeks)

Secondary Outcomes (3)

• Changes in Viral Load

  At the end of Cycle 4 (each cycle is 3 weeks)

• Change in Cytokine Secretion Assays

  36 months

• Correlation of Multiplex IHC to response

  36 months

Study Arms (1)

durvalumab (MEDI4736) and tremelimumab

EXPERIMENTAL

Durvalumab in combination with tremelimumab and platinum-based doublet chemotherapy. Only subjects who achieve stable disease or better radiological response after 4 cycles of induction treatment will be eligible to continue study treatment with durvalumab in maintenance.

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

durvalumab 1500 mg, intravenous, every 3 weeks for 4 cycles, followed by 1500 mg, intravenous, every 4 weeks (maintenance treatment)

durvalumab (MEDI4736) and tremelimumab

Tremelimumab DRUG

tremelimumab 75 mg, intravenous, every 3 weeks for 4 cycles. A dose of tremelimumab 75 mg will be given at week 16.

durvalumab (MEDI4736) and tremelimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with stage IV NSCLC who had undergone no previous systemic therapy for stage IV disease.
• Patients with HIV must be on an effective combination anti-retroviral therapy (cART) regimen for ≥ 4 weeks. Also, patients need to meet the following criteria.
• Documented HIV viral load \< 400 copies/mL
• No AIDS-defining opportunistic infections within the last 12 months
• No concurrent incurable AIDS-defining malignancy
• Age \> 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Body weight \>30kg
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1,000 per mm3
• Platelet count ≥ 100,000 per mm3
• CD4 T-cell count ≥ 100 per mm3 for HIV-infected patients
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN

You may not qualify if:

• Sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q) and/or ALK translocations by locally approved laboratory testing including blood-based liquid biopsy.
• \. Coinfection of HIV + HBV (coinfection of HIV and HBV allowed if the patient is on appropriate anti-viral therapy for HBV) or HIV + HCV (coinfection of HIV and HCV allowed if HCV is cured or patient is on appropriate anti-viral therapy for hepatitis C). Coinfection of HBV and HCV is allowed if otherwise eligible.
• No measurable disease.
• Receipt of the last dose of anticancer therapy (chemotherapy, targeted therapy) ≤ 21 days prior to the first dose of study treatment.
• Patients who have had whole brain radiation therapy (WBRT) during the previous 2 weeks before treatment (no washout period is required for patients who have received stereotactic body radiation therapy).
• Subject has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to starting study drug or has not recovered from side effects of such procedure (≥ grade 2 AE related to such procedure). Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and subject can be enrolled in the study ≥ 1 week after the procedure.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• i. Patients with vitiligo or alopecia ii. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement iii. Any chronic skin condition that does not require systemic therapy iv. Patients without active disease in the last 5 years may be included
• 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 or compromise the ability of the patient to give written informed consent.
• Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Previously untreated central nervous system (CNS) metastases or leptomeningeal disease. Patients who have had whole brain radiation therapy (WBRT) during the previous 2 weeks before treatment (no washout period is required for patients who have received stereotactic body radiation therapy).
• Active tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice).
• Current or prior use of immunosuppressive medication within 7 days before the first dose of durvalumab. The following are exceptions to this criterion:
• i. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) ii. Systemic corticosteroids at doses not to exceed 20 mg/day of prednisone or its equivalent iii. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) iv. Decreasing dose of systemic corticosteroids after radiation therapy for brain metastasis.

Sponsors & Collaborators

• AstraZeneca: collaborator
• Georgetown University: lead

Study Sites (4)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Marlene and Stewart Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

Harry and Jeannette Weinberg Cancer Institute at Franklin Square

Baltimore, Maryland, 21237, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Chul Kim, MD

  Georgetown University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: August 5, 2020
• Study Start: December 9, 2020
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)