A Study of Tolododekin Alfa (ANK-101) in Combination With an Anti-PD-1/PD-L1 Antibody in Participants With Advanced Non-Small Cell Lung Cancer

Official title

A Phase 1b, Two-Part Study of Tolododekin Alfa (ANK-101) in Combination With an Anti-PD-1/PD-L1 Antibody in Participants With Advanced Non-Small Cell Lung Cancer

Overview

A study of tolododekin alfa (also known as ANK-101) administered in combination with an anti-programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibody in participants with advanced or metastatic non-small cell lung cancer (NSCLC). Cohort A will enroll participants who have progressed on prior standard of care treatment with an anti-PD-1/PD-L1 antibody and a platinum-based chemotherapy regimen. Cohort B will enroll participants who are treatment-naïve for locally advanced or metastatic NSCLC.

Interventions

• Drug tolododekin alfa
  Participants will receive tolododekin alfa as an intratumoral injection every 3 weeks (Q3W).
• Drug Cetrelimab
  Participants will receive cetrelimab Q3W.

Primary outcome measures

• Objective Response Rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 [Time frame: 6 months]

Secondary outcome measures (12)

• Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Time frame: 6 months]
• Duration of Response (DoR) [Time frame: 6 months]
• Disease Control Rate (DCR) [Time frame: 6 months]
• Progression Free Survival (PFS) [Time frame: 6 months]
• Overall Survival (OS) [Time frame: 6 months]
• Lesion-level response in injected and noninjected lesions [Time frame: 6 months]
• Measure of area under the plasma concentration-time curve (AUC) of tolododekin alfa [Time frame: 6 months]
• Measure of maximum plasma concentration (Cmax) of tolododekin alfa [Time frame: 6 months]
• Measure of time to maximum concentration (Tmax) of tolododekin alfa [Time frame: 6 months]
• Measure of volume of distribution adjusted for bioavailability (Vd/F) of tolododekin alfa [Time frame: 6 months]
• Measure of terminal half-life (t1/2) of tolododekin alfa [Time frame: 6 months]
• Incidence of treatment-emergent anti-drug antibodies (ADA) of tolododekin alfa [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• Have confirmed locally advanced or metastatic NSCLC
• Thyroid-stimulating hormone (TSH) within normal limits
• Have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1
• Have a life expectancy > 12 weeks
• Have baseline electrocardiogram (ECG) without evidence of acute ischemia or prolonged QT interval
• Heterosexually active women of childbearing potential (WOCBP) must agree to use at least 2 forms of highly effective methods of contraception
• All male participants who are not sterile must commit to the use of a reliable method of birth control or abstinence
• Human immunodeficiency virus (HIV)-infected participants must be on anti-retroviral therapy (ART) and have well-controlled HIV infection/disease
• Resolution of all prior anticancer therapy toxicities to ≤ Grade 1 prior to C1D1.
• Willingness to provide fresh tumor biopsy specimens
• Capable of understanding and complying with protocol requirements
• Provides written informed consent for the study

Exclusion criteria

• Cohort A only: Participants with Grade 3 or higher toxic effects to manage adverse events from previous treatment with immunotherapy
• Cohort B only: Prior therapy with an immune checkpoint inhibitor.
• Have known EGFR or ALK mutations
• Have had prior treatment with recombinant interleukin-12 (IL-12)
• Have received short-term systemic therapy with immunosuppressive agents prior to C1D1
• Have active autoimmune disease or medical conditions requiring chronic steroid or other immunosuppressive therapy prior toC1D1
• Have received live vaccines within 28 days prior to C1D1
• Have primary or acquired immunodeficient states
• Women of childbearing potential who has a positive serum pregnancy test prior to C1D1 or female participant who is breastfeeding
• Have a history of allogeneic tissue/solid organ transplant
• Has known active uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV).
• HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease
• Have known active central nervous system metastases
• Have congestive heart failure, active coronary artery disease, unevaluated new onset angina, unstable angina, or clinically significant cardiac arrhythmias.
• Have uncontrolled bleeding disorders prior to C1D1
• Participants on coumadin (warfarin), due to potential for increased bleeding risk associated with surgery
• History of noninfectious pneumonitis within the previous 5 years
• Cohort A only: History of allergy to protein-based therapies, history of any significant drug allergy, or known allergies, hypersensitivity, or intolerance to cetrelimab excipients OR Cohort B only: Hypersensitivity to any component of the anti-PD-1/PD-L1 antibody selected as standard of care
• Have other systemic conditions or organ abnormalities that may interfere with the conduct of the study
• Have any acute or chronic psychiatric problems or substance abuse disorder that make the participant unsuitable for participation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 5 centers

• Community Health Network — Indianapolis
• Barbara Ann Karmanos Cancer Hospital — Detroit
• Roswell Park Comprehensive Cancer Center — Buffalo
• Icahn School of Medicine at Mount Sinai — New York
• FirstHealth of the Carolinas — Pinehurst

Identifiers

NCT: NCT07027514 · ANK-101-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗