A Phase 1b Neoadjuvant Trial of Sirolimus Followed by Durvalumab (MEDI4736) in Resectable Non-small Cell Lung Cancer
Overview
- Phase
- Phase 1
- Intervention
- Durvalumab
- Conditions
- Lung Non-Small Cell Carcinoma
- Sponsor
- Emory University
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This trial studies the side effects of sirolimus and durvalumab and to see how well they work in treating patients with stage I-IIIA non-small cell lung cancer. Sirolimus is an oral medication that blocks the mTOR cellular pathway which may help the immune system work better. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving sirolimus before durvalumab may help the immune system get rid of cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of sirolimus followed by durvalumab as neoadjuvant treatment II. To evaluate the efficacy of sirolimus followed by durvalumab as neoadjuvant treatment for stage I, II, and IIIA non-small cell lung cancer (NSCLC) SECONDARY OBJECTIVES: I. To evaluate the efficacy of sirolimus in combination with durvalumab as neoadjuvant treatment for stage I, II, and IIIA NSCLC II. To evaluate response to sirolimus in combination with durvalumab in patients with PD-L1-positive versus (vs.) PD-L1-negative tumors III. To evaluate the association between blood mutation burden and response to sirolimus and durvalumab EXPLORATORY OBJECTIVES: I. To evaluate the immune-mediated effects of combination sirolimus and durvalumab II. To investigate tumor and immune microenvironment changes in tissue samples OUTLINE: Patients receive sirolimus orally (PO) once daily (QD) on days 1-21 in the absence of disease progression or unacceptable toxicity. Starting on day 22, patients receive durvalumab intravenously (IV) over 1 hour. Treatment with durvalumab repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Within a 2-3 week period after the second dose of durvalumab, but not earlier than two weeks after the administration of durvalumab, patients undergo standard of care surgery. After completion of study treatment, patients are followed up every 3 months for 2 years.
Investigators
Jennifer Carlisle
Principal Investigator
Emory University
Eligibility Criteria
Inclusion Criteria
- •Patients with pathologically documented NSCLC: Stage I, II, IIIa NSCLC based on 8th edition of American Joint Committee on Cancer (AJCC) Non-small cell Lung Cancer Staging system
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the United States \[US\]) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy of \>= 26 weeks
- •Body weight \> 30 kg
- •Hemoglobin \>= 9.0 g/dL
- •Absolute neutrophil count (ANC) 1.5 x 10\^9/L (\>= 1500 per mm\^3)
- •Platelet count \>= 100 x 10\^9/L (\>= 100,000 per mm\^3)
- •Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =\< 5 x ULN
Exclusion Criteria
- •Patients who have had prior therapy for lung cancer including chemotherapy, hormonal therapy, or radiotherapy
- •Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study
- •Prior treatment with anti-PD-1, anti-PDL-1, other PD-1/PDL-1 pathway targeting agents, or mTOR inhibition
- •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:
- •Patients with vitiligo or alopecia
- •Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
- •Any chronic skin condition that does not require systemic therapy
- •Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- •Patients with celiac disease controlled by diet alone
Arms & Interventions
Treatment (sirolimus, durvalumab)
Patients receive sirolimus PO QD on days 1-21 in the absence of disease progression or unacceptable toxicity. Starting on day 22, patients receive durvalumab IV over 1 hour. Treatment with durvalumab repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Within a 2-3 week period after the second dose of durvalumab, but not earlier than two weeks after the administration of durvalumab, patients undergo standard of care surgery.
Intervention: Durvalumab
Treatment (sirolimus, durvalumab)
Patients receive sirolimus PO QD on days 1-21 in the absence of disease progression or unacceptable toxicity. Starting on day 22, patients receive durvalumab IV over 1 hour. Treatment with durvalumab repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Within a 2-3 week period after the second dose of durvalumab, but not earlier than two weeks after the administration of durvalumab, patients undergo standard of care surgery.
Intervention: Sirolimus
Outcomes
Primary Outcomes
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0
Time Frame: at time of surgery
Other adverse events will be listed and summarized by severity, seriousness, and by system organ class. The number and percentage of subjects who experience AEs will be presented in tabular and/or graphical format and summarized descriptively, where appropriate. The frequency of overall toxicity, categorized by toxicity grades 1 through 5, will be described.
Complete Pathologic Response
Time Frame: at time of surgery
Disappearance of all invasive cancer