ALCMI-005: Pembrolizumab and Epacadostat in Treating Patients With Extensive Stage Small Cell Lung Cancer

NCT03402880 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 17202NCI-2017-01756
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies how well pembrolizumab and epacadostat work in combination treating patients with extensive stage small cell lung cancer. Monoclonal antibodies, such as pembrolizumab, may assist the immune system in recognizing cancer cells leading to elimination of those cells. Epacadostat may prevent down-regulation of T-cells, which means it can boost the immune system. Giving pembrolizumab and epacadostat together may work better than either drug alone in treating extensive stage small cell lung cancer.

Conditions

Extensive Stage Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

  Proportions and associated confidence intervals will be estimated.

  Through study completion, an average of 6 months

Secondary Outcomes (3)

• Progression free survival

  Through study completion, an average of 6 months

• Overall survival

  Up to 24 months

• Incidence of grade 3 toxicity

  Through study completion, an average of 6 months

Study Arms (1)

Treatment (pembrolizumab, epacadostat)

EXPERIMENTAL

Patients receive pembrolizumab IV on day 1 and epacadostat PO BID on days 1-21. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity. Patients benefiting from treatment may continue for an additional 17 courses.

Biological: Pembrolizumab; Drug: Epacadostat; Other: Laboratory Biomarker Analysis

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: 1374853-91-4, Immunoglobulin G4, Anti-(Human Programmed Cell Death 1), Keytruda, Lambrolizumab, MK-3475, SCH 900475, Humanized Mouse Monoclonal (228-L-proline(H10-S>P))gamma 4 Heavy Chain (134-218')-disulfide with Humanized Mouse Monoclonal Kappa Light Chain Dimer (226-226'':229-229'')-bisdisulfide

Treatment (pembrolizumab, epacadostat)

Epacadostat DRUG

Given PO

Also known as: INCB024360

Treatment (pembrolizumab, epacadostat)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, epacadostat)

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial
• Subjects with histologically or cytologically confirmed small cell lung cancer and radiographic evidence of extensive stage disease
• Previous treatment with platinum based therapy for small cell lung cancer (eligibility not dependent on stage at time of platinum based therapy)
• Have measurable disease based on RECIST v1.1
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) \>= 1,500/mcL (performed within 10 days of treatment initiation)
• Platelets \>= 100,000/mcL (performed within 10 days of treatment initiation)
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 10 days of treatment initiation)
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) (performed within 10 days of treatment initiation)
• Serum total bilirubin =\< 1.2 X ULN OR conjugated bilirubin =\< 1.2 x ULN; if an institutional ULN for conjugated bilirubin is not available, then conjugated bilirubin should be \< 40% of total bilirubin to be considered eligible (performed within 10 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases (performed within 10 days of treatment initiation)
• Albumin \>= 2.5 mg/dL (performed within 10 days of treatment initiation)
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
• Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy \> 10 mg/day prednisone equivalents or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (Bacillus tuberculosis); recommend documentation of inadequate treatment of latent or active TB
• Hypersensitivity to pembrolizumab, epacadostat or any of its excipients
• Corrected QT (QTc) \> 480 ms: history or presence of an abnormal electrocardiogram (ECG) that, in the investigators opinion, is clinically meaningful; screening QTc interval \> 480 milliseconds is excluded; in the event that a single QTc is \> 480 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is \< 480 milliseconds; for subjects with an intraventricular conduction delay (QRS interval \> 120 milliseconds), the corrected JT (JTc) interval may be used in place of the QTc with sponsor approval; the JTc must be \< 340 milliseconds if JTc is used in place of the QTc; subjects with left bundle branch block are excluded; QTc prolongation due to pacemaker may enroll if the JTc is normal
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); exceptions include vitiligo, controlled asthma, type I diabetes, Graves' disease, Hashimoto's disease, or with medical monitor approval; replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Subjects who have had prior radiotherapy within 2 weeks of therapy; subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis; a 1-week wash out is permitted for palliative radiation to non-CNS disease with medical monitor approval
• Has known history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy

Sponsors & Collaborators

• City of Hope Medical Center: lead
• Addario Lung Cancer Medical Institute: collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Interventions

pembrolizumab; Immunoglobulin G; epacadostat

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ravi Salgia, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

• Jacob Sands, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

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: November 3, 2017
• First Posted: January 18, 2018
• Study Start: December 1, 2018
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: October 10, 2018

Record last verified: 2018-10

Locations

US (3)