Immunotherapy Combination Study in Advanced Previously Treated Non-Small Cell Lung Cancer

NCT02460367 | Terminated Phase 1 DMC

• 2 other identifiers: NLG04011504-1393
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1/2 trial using indoximod, an inhibitor of the immune "checkpoint" pathway indoleamine 2,3-dioxygenase (IDO), in combination with Tergenpumatucel-L immunotherapy and Docetaxel to treat subjects with advanced Non-Small Cell Lung Cancer (NSCLC). From a practical standpoint, a successful tumor immunotherapy will likely require a combination treatment with additional therapeutic interventions that both activate an immune response and remove redundant mechanisms of tolerance maintenance. This clinical trial utilizes the combination of the chemotherapeutic agent, docetaxel, plus two investigational methods of cancer immunotherapy: the first, tergenpumatucel-L, is intended to educate the human immune system to recognize the abnormal components found in lung cancer cells, resulting in an immune response intended to destroy or block the growth of the cancer; and the second, the IDO inhibitor Indoximod, will overcome tumor-induced immune suppression. The goal of this study is to assess the progression-free survival (PFS) and overall survival (OS) rates in this patient population. This study will provide a foundation for future trials testing indoximod combined with tergenpumatucel-L.

Conditions

Non-small Cell Lung Cancer; Progression of Non-small Cell Lung Cancer; Non-small Cell Lung Cancer Recurrent

Keywords

Non-small Cell Lung Cancer; Vaccine Therapy; Immunotherapy; Second line therapy; Progressive; Relapsed; IDO; IDO Inhibitor

Outcome Measures

Primary Outcomes (2)

• Regimen Limiting Toxicity

  Phase 1 component: To identify the regimen limiting toxicity (RLT) for the combination of tergenpumatucel-L and indoximod.

  Approximately 6 weeks

• Progression Free Survival (PFS)

  Approximately 18 months

Secondary Outcomes (4)

• Frequency and grade of adverse events of tergenpumatuucel-L, indoximod and docetaxel

  Approximately 18 months

• Objective Response Rate

  Approximately 18 months

• Overall Survival

  Approximately 30 months

• Response rate to subsequent therapy

  up to 36 months

Study Arms (1)

Phase 1: Dose Escalation

EXPERIMENTAL

Up to 18 participants will be enrolled and treated at escalating doses of Indoximod with a fixed dose of tergenpumatucel-L and docetaxel. Treatment may continue until definitive disease progression or significant toxicology.

Drug: Docetaxel; Biological: Tergenpumatucel-L; Drug: Indoximod

Interventions

Docetaxel DRUG

Also known as: Taxotere®

Phase 1: Dose Escalation

Tergenpumatucel-L BIOLOGICAL

Also known as: HyperAcute®-Lung Immunotherapy

Phase 1: Dose Escalation

Indoximod DRUG

Also known as: D-1MT, 1-methyl-D-tryptophan

Phase 1: Dose Escalation

Eligibility Criteria

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

You may qualify if:

• Histological/cytological diagnosis of non-small cell lung cancer (NSCLC). Squamous cell (epidermoid), adenocarcinoma, bronchoalveolar carcinoma and large cell anaplastic lung carcinoma histologies are eligible. Mixed histologies of NSCLC (i.e., adenosquamous) are eligible. Mixed NSCLC/small cell lung carcinoma (SCLC), and variant large and small cell lung cancer are NOT eligible for this study.
• Measurable disease as defined by RECIST 1.1 Criteria.
• At least one but no more than three prior lines of therapy in the advanced stage are allowed. One prior line of therapy must be platinum doublet chemotherapy.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Normal bone marrow and organ function as defined below:
• Marrow: Hemoglobin ≥10.0 gm/dL, absolute granulocyte count (AGC) ≥1,000/mm3 platelets ≥100,000/mm3, absolute lymphocyte count ≥1000/mm3.
• Hepatic: Serum/plasma total bilirubin ≤1.5 x upper limit of normal (ULN) with the exception of \<2.9 mg/dL for patients with Gilbert's disease, ALT (SGPT) and AST (SGOT) ≤2.5 x ULN.
• Renal: Serum/plasma creatinine (sCr) ≤1.5 x upper limit of normal, or creatinine clearance (Ccr) ≥50 mL/min.
• Serum/plasma albumin \> 3.0 gm/dL
• Sexually active women of child-bearing potential must agree to use two forms of contraception prior to study entry and for the duration of study participation. A pregnancy test is required prior to study enrollment and monthly while on treatment with indoximod for all women of child- bearing potential. Also men should be discouraged from fathering children while on treatment.
• Ability to understand and willingness to sign an IRB approved written informed consent document.

You may not qualify if:

• More than three lines of prior therapy.
• Previous use of indoximod or tergenpumatucel-L immunotherapy.
• A history of other malignancy, unless treated with curative intent, and no evidence of disease for at least 2 years.
• Current therapy with any other investigational agents.
• Untreated CNS disease, metastases or carcinomatous meningitis. Patients with CNS metastases must be at least 2 weeks status post prior therapy to the brain and be off all steroids without progressing CNS disease or symptoms.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to indoximod, docetaxel, or other agents used in the study.
• Current use of immunosuppressive drugs or use of corticosteroids, except for inhaler, topical corticosteroids, or dexamethasone in the premedication for docetaxel.
• Other malignancy within three years, unless the probability of recurrence of the prior malignancy is \<5%. Patient's curatively treated for squamous cell carcinoma and basal cell carcinoma of the skin and carcinoma in situ of the uterine cervix (CIN) or patients with a history of malignant tumor in the past that have been disease free for at least five years are also eligible for this study.
• History of organ transplant.
• Any of the following within 6 months prior to study drug administration:
• Myocardial infarction
• Severe/unstable angina
• Coronary/peripheral artery bypass graft
• Symptomatic congestive heart failure
• Cerebrovascular accident or transient ischemic attack

Sponsors & Collaborators

• NewLink Genetics Corporation: lead

Study Sites (2)

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Recurrence

Interventions

Docetaxel; 1-methyltryptophan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Gene Kennedy, MD

  NewLink Genetics Corporation

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 21, 2015
• First Posted: June 2, 2015
• Study Start: January 1, 2016
• Primary Completion: July 17, 2017
• Study Completion: January 13, 2021
• Last Updated: April 6, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)