A Trial of CDX-1401 in Combination With Poly-ICLC and Pembrolizumab, in Previously Treated Advanced Solid Tumor Patients

NCT02661100 | Withdrawn Phase 1 DMC

• 1 other identifier: CASE2Y16
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will look at the safety of the combination of three drugs (CDX-1401, Poly-ICL, and Pembrolizumab) and its effect on decreasing tumors. Pembrolizumab is an experimental cancer drug. CDX-1401 is a tumor specific antigen and Poly-ICL is a Toll-like receptor agonist tumor specific antigens which when combined with Pembrolizumab may increase the tumor response to this drug.

Conditions

Non Small Cell Lung Cancer; Advanced Triple Negative Breast Cancer; Small Cell Lung Cancer; Urothelial Cancer; Mesothelioma; Malignant Melanoma

Keywords

Vaccine; NY-ESO-1; DEC-205; Poly-ICLC; Pembrolizumab; Cancer

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity

  Dose limiting toxicity (DLT) will be defined as any side effects which are attributable to the study treatment during the first 28 days of therapy (Cycle 1). The dose limiting toxicity will be based on the tolerability observed during treatment.

  Up to 28 days of therapy (Cycle 1)

Secondary Outcomes (5)

• Objective Response Rate for combination therapy

  Up to 24 months after beginning treatment

• Median Duration of Response

  Up to 24 months after beginning treatment

• Median time to tumor response

  Up to 24 months after beginning treatment

• Median time of progression free survival

  Up to 24 months after beginning treatment

• Median Overall Survival

  Up to 24 months after beginning treatment

Study Arms (1)

CDX-1401 + Poly-ICLC + Pembrolizumab followed by Pembrolizumab

EXPERIMENTAL

Patients receive CDX-1401, Poly-ICLC and Pembrolizumab for 4 cycles (Q 3 weeks) followed by Pembrolizumab alone (Q 3 weeks) until disease progression.

Drug: Pembrolizumab; Biological: CDX-1401; Biological: Poly-ICLC

Interventions

Pembrolizumab DRUG

200mg/kg by IV infusion on Day 1 of each 3 week cycle. Given until disease progression

CDX-1401 + Poly-ICLC + Pembrolizumab followed by Pembrolizumab

CDX-1401 BIOLOGICAL

1mg given subcutaneously on day 1 of each 3 week cycle. Given for 4 cycles

CDX-1401 + Poly-ICLC + Pembrolizumab followed by Pembrolizumab

Poly-ICLC BIOLOGICAL

2mg given subcutaneously on day 1 and 2 of each 3 week cycle. Given for 4 cycles

CDX-1401 + Poly-ICLC + Pembrolizumab followed by Pembrolizumab

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.
• Patients with previously treated advanced lung cancer (NSCLC, SCLC and mesothelioma), advanced triple negative breast cancer, urothelial cancers and malignant melanoma. Tumors should be positive for expression of NY-ESO-1, as assessed by external central laboratory testing.
• Malignancy that has progressed after any therapies with curative potential or at least one approved palliative therapy for which the patient is a candidate. Patients with metastatic melanoma may be enrolled without prior treatment provided they meet rest of the eligibility criteria.
• Where applicable, chemotherapy or radiation therapy must have been completed at least 4 weeks prior to the first dose of study treatment; the interval for prior anticancer therapeutic radiopharmaceuticals is at least 8 weeks. For patients on small molecule tyrosine kinase inhibitors therapy must have been completed 14 days prior to start of study treatment. The patient must have adequately recovered from any clinically significant toxicity experienced during prior treatment(s) in the investigator's opinion.
• Chemoembolization, surgery or any other local therapy completed at least 4 weeks prior to the first dose of study treatment.
• Have measurable disease based on immune-related Response Criteria (irRC).
• Availability of tumor tissue (preferably from a recent biopsy or resection, or if not available, on the archived tumor tissue from the primary resection) for NY-ESO-1 expression analysis. Positive NY-ESO-1 expression will be required for entry. NY-ESO-1 expression will be analyzed at a central laboratory.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• \. Demonstrate adequate organ function as defined below , all screening labs should be performed within 10 days of treatment initiation.
• Absolute neutrophil count (ANC) \>=1,500/mcL
• Platelets \>= 100,00/mcL
• Hemoglobin \>= 9g/dL or \>= 5.6mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• Serum creatinine =\< 1.5X upper limit of normal
• Measured creatinine clearance \>=mL/min for subject with creatinine levels \>1.5 X institutional upper limit of normal
• Serum total bilirubin =\< 1.5X upper limit of normal

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 or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active bacillus tuberculosis
• Hypersensitivity to Pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (ie =\< 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 (ie =\< Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Has a known additional malignancy that is progressing or required 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 metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided therapy are stable (without evidence of progression by imagining 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 (ie with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not the best interest of the subject to participate, in the opinion of the treating investigator.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent and previous administration of vaccine therapy targeting NY-ESO-1.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Mesothelioma; Melanoma; Neoplasms

Interventions

pembrolizumab; poly ICLC

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Vamsidhar Velcheti, MD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 19, 2016
• First Posted: January 22, 2016
• Study Start: January 1, 2017
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: December 7, 2016

Record last verified: 2016-12