Tolododekin alfa (ANK-101) plus anti-PD-1/PD-L1 antibody for advanced non-small cell lung cancer

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

This trial will try tolododekin alfa (ANK-101) together with an anti-PD-1/PD-L1 antibody in people with advanced or metastatic non-small cell lung cancer, with one group previously treated with PD-1/PD-L1 plus platinum chemotherapy and another group who are treatment-naïve.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ankyra Therapeutics, Inc (industry)
• Drugs / interventions: cetrelimab, immunotherapy, chemotherapy
• Locations: 5 sites (Indianapolis, Indiana and 4 other locations)
• Trial ID: NCT07027514 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional trial combines tolododekin alfa (ANK-101) with an anti-PD-1/PD-L1 antibody (cetrelimab) in participants with locally advanced or metastatic NSCLC. The study enrolls two cohorts: Cohort A includes patients who progressed after prior anti-PD-1/PD-L1 therapy plus platinum-based chemotherapy, and Cohort B includes treatment-naïve patients. Primary Phase 1 goals focus on safety, tolerability, dose selection, and preliminary anti-tumor activity measured by RECIST v1.1, with required baseline measures such as ECG, TSH, measurable disease, ECOG 0–1, and a fresh tumor biopsy. The trial is being conducted at multiple U.S. cancer centers and requires regular on-site visits for treatment and monitoring.

Who should consider this trial

Good fit: Ideal candidates are adults with measurable, locally advanced or metastatic NSCLC, ECOG performance status 0–1, life expectancy greater than 12 weeks, and who meet cohort-specific prior-treatment criteria (either progressed after PD-1/PD-L1 plus platinum chemotherapy or treatment-naïve).

Not a fit: Patients with ECOG performance status greater than 1, unresolved toxicities from prior therapies, inability or unwillingness to provide a fresh tumor biopsy, or uncontrolled cardiac, thyroid, or infectious conditions are unlikely to be eligible or to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could increase response rates or overcome resistance to PD-1/PD-L1 therapy for some patients with advanced NSCLC.

How similar studies have performed: Other early-phase trials combining immune-modulating agents with PD-1/PD-L1 inhibitors have shown mixed but sometimes promising signals, while tolododekin alfa remains a novel and experimental approach.

Eligibility criteria

Inclusion Criteria:

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

Exclusion Criteria:

1. Cohort A only: Participants with Grade 3 or higher toxic effects to manage adverse events from previous treatment with immunotherapy
2. Cohort B only: Prior therapy with an immune checkpoint inhibitor.
3. Have known EGFR or ALK mutations
4. Have had prior treatment with recombinant interleukin-12 (IL-12)
5. Have received short-term systemic therapy with immunosuppressive agents prior to C1D1
6. Have active autoimmune disease or medical conditions requiring chronic steroid or other immunosuppressive therapy prior toC1D1
7. Have received live vaccines within 28 days prior to C1D1
8. Have primary or acquired immunodeficient states
9. Women of childbearing potential who has a positive serum pregnancy test prior to C1D1 or female participant who is breastfeeding
10. Have a history of allogeneic tissue/solid organ transplant
11. Has known active uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV).
12. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease
13. Have known active central nervous system metastases
14. Have congestive heart failure, active coronary artery disease, unevaluated new onset angina, unstable angina, or clinically significant cardiac arrhythmias.
15. Have uncontrolled bleeding disorders prior to C1D1
16. Participants on coumadin (warfarin), due to potential for increased bleeding risk associated with surgery
17. History of noninfectious pneumonitis within the previous 5 years
18. 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
19. Have other systemic conditions or organ abnormalities that may interfere with the conduct of the study
20. Have any acute or chronic psychiatric problems or substance abuse disorder that make the participant unsuitable for participation

Where this trial is running

Indianapolis, Indiana and 4 other locations

• Community Health Network — Indianapolis, Indiana, United States (RECRUITING)
• Barbara Ann Karmanos Cancer Hospital — Detroit, Michigan, United States (RECRUITING)
• Roswell Park Comprehensive Cancer Center — Buffalo, New York, United States (RECRUITING)
• Icahn School of Medicine at Mount Sinai — New York, New York, United States (RECRUITING)
• FirstHealth of the Carolinas — Pinehurst, North Carolina, United States (RECRUITING)

Study contacts

• Study coordinator: Ankyra Therapeutics

Conditions: Non Small Cell Lung Cancer