Study of AGEN1884 With Pembrolizumab in 1L NSCLC

NCT03411473 | Terminated Phase 2 DMC

• 1 other identifier: C-500-03
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 5

Brief Summary

A Phase IIa Open-Label Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN1884 in Combination with Pembrolizumab in Subjects with Chemotherapy Naïve, PD-L1 high, metastatic Non-Small Cell Lung Cancer (NSCLC)

Conditions

NSCLC Stage IV

Outcome Measures

Primary Outcomes (1)

• Occurrence of DLTs in subjects in the Safety Run-in Phase of the trial

  Occurrence of DLTs in subjects in the Safety Run-in Phase of the trial

  21 days

Secondary Outcomes (9)

• Frequency, severity, and duration of treatment-emergent AEs (TEAEs)

  116 weeks

• Frequency, severity, and duration of treatment-related AEs

  116 weeks

• Confirmed BOR per RECIST 1.1

  116 weeks

• Duration of response per RECIST 1.1

  36 months

• PFS time

  36 months

Study Arms (1)

AGEN1884 with pembrolizumab

EXPERIMENTAL

AGEN1884 in combination with pembrolizumab

Biological: AGEN1884 in combination with pembrolizumab

Interventions

AGEN1884 in combination with pembrolizumab BIOLOGICAL

AGEN1884 in combination with pembrolizumab in subjects with stage IV NSCLC whose tumors have high PD-L1 expression and no EGFR or ALK genomic tumor aberrations

AGEN1884 with pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Voluntarily agree to participate.
• Be ≥18 years of age.
• Have a histologically or cytologically confirmed diagnosis of NSCLC, is stage IV, does not have an EGFR sensitizing (activating) mutation or ALK translocation, and has not received prior systemic chemotherapy treatment for their metastatic NSCLC.
• Have measurable disease based on RECIST 1.1 as determined by the site.
• Have a life expectancy of at least 3 months and a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
• Have adequate organ function as indicated by the following laboratory values:
• Adequate hematological function defined by absolute neutrophil count (ANC) \> 1.5 x 109/L, platelet count \> 100 x 109/L, and hemoglobin \> 9 g/dL (without transfusions within 2 weeks of first dose).
• Adequate hepatic function based by a total bilirubin level \< the institutional upper limit of normal (IULN), aspartate aminotransferase (AST) level \< 1.5 x IULN, alanine aminotransferase (ALT) level \< 1.5 x IULN, and alkaline phosphatase ≤ 2.5 ULN.
• Adequate renal function defined as Creatinine ≤ 1.5 x IULN OR calculated creatinine clearance \> 60 mL/min for subjects with creatinine levels \> 1.5 x IULN (If no local guideline is available, creatinine clearance should be calculated using the Cockcroft-Gault Method).
• Adequate coagulation defined by international normalized ratio (INR) or prothrombin time ≤ 1.5 x IULN (unless the subject is receiving anticoagulant therapy); and activated partial thromboplastin time (aPTT) ≤ 1.5 x IULN (unless the subject is receiving anticoagulant therapy)
• Adequate endocrine function defined by thyroid stimulating hormone (TSH) within normal limits. Note: if TSH is not within normal limits at baseline, the subject may still be eligible if T3 and free T4 are within normal limits.
• Subject has no history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
• Have provided a formalin fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of metastatic disease has been made AND from a site not previously irradiated to assess for PD-L1 status.
• The subject's tumor does not harbor an EGFR sensitizing (activating) mutation or ALK translocation.
• The subject's tumor must have high PD-L1 expression (TPS ≥50%) as determined by an FDA-approved test.

You may not qualify if:

• Has an EGFR sensitizing mutation and/or an ALK translocation.
• Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.
• Is receiving systemic steroid therapy \< 3 days prior to the first dose of trial treatment or receiving any other form of immunosuppressive medication.
• Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection)
• Has received prior systemic cytotoxic chemotherapy, biological therapy, OR major surgery within 3 weeks of the first dose of trial treatment; received thoracic radiation therapy of \> 30 Gy within 6 months of the first dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Has central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period OR identified prior to signing the ICF.
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has had an allogeneic tissue/solid organ transplant.
• Has interstitial lung disease (ILD) OR has had a history of pneumonitis that has required oral or IV steroids.
• Has received or will receive a live vaccine within 30 days prior to the first administration of study medication. Seasonal flu vaccines that do not contain a live virus are permitted
• Has an active infection requiring intravenous systemic therapy.
• Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has known active Hepatitis B, Hepatitis C or tuberculosis.

Sponsors & Collaborators

• Agenus Inc.: lead

Study Sites (5)

Mater Research

Brisbane, Australia

Location

Scientia Clinical Research

Sydney, Australia

Location

John Flynn Private Hospital

Tugun, Australia

Location

Sydney Adventist

Wahroonga, Australia

Location

Auckland City Hospital

Auckland, New Zealand

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Medical Director

  Agenus Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 14, 2017
• First Posted: January 26, 2018
• Study Start: October 4, 2017
• Primary Completion: May 1, 2018
• Study Completion: March 1, 2019
• Last Updated: June 2, 2020

Record last verified: 2020-05

Locations

NZ (1); AU (4)