Durvalumab, Tremelimumab, and Selumetinib in Treating Participants With Recurrent or Stage IV Non-small Cell Lung Cancer

NCT03581487 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 2017-0888NCI-2018-01098
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the best dose of selumetinib and how well it works with durvalumab and tremelimumab in treating participants with stage IV non-small cell lung cancer or that has come back. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving durvalumab, tremelimumab and selumetinib may work better in treating participants with non-small lung cancer.

Conditions

Recurrent Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) (dose-escalation phase)

  The standard 3+3 design will be applied to determine the MTD among the three pre-defined dose levels.

  Up to 2 years

• Progression free survival time (PFS) (dose expansion phase)

  The estimated PFS will be provided with 95% confidence interval. Will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on PFS.

  From start of treatment assessed up to 2 years

Secondary Outcomes (4)

• Response rate by Response Evaluation Criteria in Solid Tumors 1.1

  Up to 2 years

• Disease control rate (complete response + partial response + stable disease)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Incidence of adverse events

  Up to 2 years

Study Arms (2)

Arm I (intermittent selumetinib, durvalumab, tremelimumab)

EXPERIMENTAL

Participants receive selumetinib PO BID on days 1-7 and 15-21 and durvalumab intravenously (IV) over 60 minutes on day 1. Participants also receive tremelimumab IV over 60 minutes on day 1 for courses 1-4. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Durvalumab; Drug: Selumetinib; Biological: Tremelimumab

Arm II (continuous selumetinib, durvalumab, tremelimumab)

EXPERIMENTAL

Participants receive selumetinib PO BID on days 1-28 and durvalumab IV over 60 minutes on day 1. Participants also receive tremelimumab IV over 60 minutes on day 1 for courses 1-4. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Durvalumab; Drug: Selumetinib; Biological: Tremelimumab

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Arm I (intermittent selumetinib, durvalumab, tremelimumab); Arm II (continuous selumetinib, durvalumab, tremelimumab)

Selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD6244, MEK inhibitor AZD6244

Arm I (intermittent selumetinib, durvalumab, tremelimumab); Arm II (continuous selumetinib, durvalumab, tremelimumab)

Tremelimumab BIOLOGICAL

Given IV

Also known as: Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206, Ticilimumab

Arm I (intermittent selumetinib, durvalumab, tremelimumab); Arm II (continuous selumetinib, durvalumab, tremelimumab)

Eligibility Criteria

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

You may qualify if:

• Written informed consent and any locally-required authorization will be obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• Histologically or cytologically confirmed recurrent non-small cell lung cancer not amenable to curative intent therapy or stage IV NSCLC
• Known KRAS mutation status by Clinical Laboratory Improvement Act (CLIA) certified test
• Documented progression following at least one line of chemotherapy or immunotherapy for metastatic or recurrent disease, or progression within 6 months of receiving adjuvant chemotherapy or concurrent chemotherapy for early stage or locally advanced disease
• Biopsy accessible disease and willingness to undergo tumor biopsy
• Measurable disease by RECIST 1.1
• Total body weight \> 30 kg
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Ability to take pills by mouth
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9.0 g/dL
• Total bilirubin total bilirubin =\<1.5 x upper limit of normal (ULN) (higher is allowed if in the setting of known Gilbert's disease)

You may not qualify if:

• Have received or are receiving an investigational medicinal product (IMP) or other systemic anticancer treatment within 4 weeks prior to the first dose of study treatment, or within a period during which the IMP or systemic anticancer treatment has not been cleared from the body (e.g. a period of 5 'half-lives'), whichever is the most appropriate and as judged by the Investigator
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Current or prior use of immunosuppressive medication within 14 days of the 1st dose of durvalumab, with the exception of intranasal and inhaled corticosteroids or oral corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
• Receipt of radiation therapy within 4 weeks prior to starting study treatment. Limited field of radiation for palliation at any time prior to the start of study treatment is acceptable if: a) the lung is not in the radiation field, b) the irradiated lesions are not used as target lesions
• Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
• Prior treatment with a MEK, Ras, or Raf inhibitor
• Patients who have received prior anti PD-1, anti PD-L1 or anti CTLA-4 a) must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy. b) all adverse events (AEs) while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study c) must not have experienced a \>= grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of =\< grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic
• Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day
• Patients who are receiving any other investigational agents
• Known hypersensitivity to selumetinib, durvalumab, tremelimumab or any excipient or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib, tremelimumab or durvalumab
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g., colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis), 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: a) patients with vitiligo or alopecia, b) patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement, c) any chronic skin condition that does not require systemic therapy, d) patients without active disease in the last 5 years may be included but only after consultation with the study physician, e) patients with celiac disease controlled by diet alone
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis \[TB\] testing in line with local practice), hepatitis B (known positive hepatitis B virus \[HBV\] surface antigen \[HBsAg\] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
• History of leptomeningeal carcinomatosis
• Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, has been treated with surgery and / or radiation, and has been stable without requiring corticosteroids nor anti-convulsant medications for at least 4 weeks prior to the first dose of study medication

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

durvalumab; Immunoglobulin G; Disulfides; AZD 6244; tremelimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Don L Gibbons

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2018
• First Posted: July 10, 2018
• Study Start: April 1, 2019
• Primary Completion: October 30, 2025
• Study Completion: October 30, 2025
• Last Updated: November 5, 2025

Record last verified: 2025-10

Locations

US (1)