Non Small Cell Lung Cancer
Conditions
Brief summary
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
DRUGtolododekin alfa
Participants will receive tolododekin alfa as an intratumoral injection every 3 weeks (Q3W).
DRUGCetrelimab
Participants will receive cetrelimab Q3W.
Sponsors
Ankyra Therapeutics, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 | 6 months | Percentage of participants with complete response (CR) or partial response (PR) among all response evaluable participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) | 6 months | Time from first CR/PR to the date of progressive disease (PD) or death. |
| Disease Control Rate (DCR) | 6 months | The percentage of participants with stable disease, complete response or partial response among all response evaluable participants |
| Progression Free Survival (PFS) | 6 months | The duration from the first dose of tolododekin alfa until PD/death |
| Overall Survival (OS) | 6 months | The length of time participants remain alive starting from the first dose of tolododekin alfa |
| Lesion-level response in injected and noninjected lesions | 6 months | Measure response in injected and noninjected lesions |
| Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | 6 months | Number of participants with adverse events (TEAEs, SAEs) |
| Measure of maximum plasma concentration (Cmax) of tolododekin alfa | 6 months | Characterize pharmacokinetic (PK) parameter Cmax after IT injection of tolododekin alfa |
| Measure of time to maximum concentration (Tmax) of tolododekin alfa | 6 months | Characterize pharmacokinetic (PK) parameter Tmax after IT injection of tolododekin alfa |
| Measure of volume of distribution adjusted for bioavailability (Vd/F) of tolododekin alfa | 6 months | Characterize pharmacokinetic (PK) parameter Vd/F after IT administration of tolododekin alfa |
| Measure of terminal half-life (t1/2) of tolododekin alfa | 6 months | Characterize pharmacokinetic (PK) parameter t1/2 after IT administration of tolododekin alfa |
| Incidence of treatment-emergent anti-drug antibodies (ADA) of tolododekin alfa | 6 months | Quantification of ADAs after IT administration of tolododekin alfa |
| Measure of area under the plasma concentration-time curve (AUC) of tolododekin alfa | 6 months | Characterize pharmacokinetic (PK) parameter AUC after IT injection of tolododekin alfa |
Countries
United States
Contacts
Primary ContactAnkyra Therapeutics
Outcome results
None listed