A Phase I Open-Label, Dose Escalation Study of the Safety and Tolerability of Tolododekin Alfa (ANK-101) in Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- tolododekin alfa
- Conditions
- Advanced Solid Tumor
- Sponsor
- Ankyra Therapeutics, Inc
- Enrollment
- 97
- Locations
- 7
- Primary Endpoint
- Incidence and characteristics of DLTs (Parts 1 and 2 only) and TEAEs
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
This is a Phase 1, multicenter, open-label dose escalation study to determine the safety and tolerability of intratumoral (IT) injection of tolododekin alfa (ANK-101) in participants with advanced solid tumors who have progressed during or after receiving standard of care (SOC) therapy or who will not benefit from such therapy. The study will be conducted in three parts; in Part 1, participants with superficial lesions will receive ANK-101 as a single agent; in Part 2, participants with visceral lesions will receive ANK-101 as a single agent; and in Part 3, participants with cutaneous squamous cell carcinoma (CSCC) will receive ANK-101 in combination with cemiplimab.
Detailed Description
This Phase 1 first-in-human (FIH) study will: 1) evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic effects and preliminary clinical activity of tolododekin alfa (ANK-101) administered as an intratumoral (IT) injection in participants with superficial or visceral lesions; 2) determine the recommended dose for expansion (RDE) of ANK-101; and 3) to determine the safety and tolerability of ANK-101 in combination with cemiplimab. For parts 1 and 2, the study design consists of six sequential dose-escalation cohorts. Part 1 will enroll participants with advanced solid tumors, with cutaneous, subcutaneous or nodal disease (accessible by clinical palpation or ultrasound guidance). Part 2 will start once the DLT period of dose level 1 in Part 1 is completed and dose level 2 is opened. Part 2 will enroll participants with visceral disease (accessible by interventional radiology or endoscopic techniques). Participants in Part 2 may also have superficial lesions that can be injected if in the Investigator's opinion this is clinically indicated. Ten participants with non-small cell lung cancer (NSCLC) will be dosed in a Part 2 dose expansion cohort at the RDE. Part 3 will start once dose escalation for Part 1 is complete and the RDE is identified. Part 3 will consist of ANK-101 in combination with cemiplimab in 15 participants with high-risk locally advanced or metastatic CSCC that have superficial lesions for injection. Participants will be treated with ANK-101 given as IT injections once every three weeks at the RDE in combination with cemiplimab. Enrollment in Part 3 will include a safety run-in of 5 participants. Following the first dose of the 5th participant, enrollment will pause for 21 days before opening enrollment to the remaining 10 participants or stopping further enrollment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •≥ 18 years of age on day of signing informed consent
- •histologically or cytologically confirmed diagnosis of cutaneous, subcutaneous, soft tissue, or nodal advanced solid tumor malignancy; metastatic disease eligible
- •measurable disease per RECIST v1.1 - Note: Must have at least 1 tumor lesion with longest dimension of ≥ 10 mm (≥ 15 mm for the short axis for malignant lymph node lesions) that - For Part 1 only: can be easily palpated or detected by ultrasound to facilitate IT injection of ANK-101 (i.e., tumor in skin, muscle, subcutaneous tissue, or accessible lymph node) or; - For Part 2 only: can be accessed by interventional radiologic or endoscopic procedures for injection (e.g., ultrasound or computed tomography \[CT\] guided). - For Part 2 Dose Expansion Cohort only: Histologically confirmed Stage III or Stage IV NSCLC
- •Part 3 CSCC Combination Cohort: Histologically confirmed high-risk locally advanced or metastatic CSCC not amenable to surgical management as determined by a multidisciplinary tumor board.
- •documented disease progression, be refractory to, or intolerant of existing SOC therapy(ies) known to provide clinical benefit (including surgical cure) or not be eligible for SOC therapy(ies)
- •ECOG performance status 0-1
- •life expectancy \> 12 weeks
- •adequate bone marrow, hepatic and renal function
- •baseline electrocardiogram (EKG) without evidence of acute ischemia or prolonged QTc interval \> 460 msec
- •Human immunodeficiency virus (HIV) infected participants must be on anti-retroviral therapy (ART) and have well-controlled HIV infection/disease
Exclusion Criteria
- •injectable tumors impinging upon major airways or blood vessels
- •prior treatment with recombinant interleukin-12 (IL-12)
- •have received systemic therapy with immunosuppressive agents ≤ 28 days before the start of treatment
- •have received live vaccines within 28 days prior to the start of ANK-101 treatment
- •have primary or acquired immunodeficient states (e.g., leukemia, lymphoma)
- •a woman of childbearing potential (WOCBP) who has a positive serum pregnancy test (within 72 hours) prior to the start of treatment or female participant who is breastfeeding
- •prior organ transplantation
- •known history of hepatitis B virus, known active hepatitis C virus, or a positive serological test at screening within 28 days prior to the start of treatment
- •HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease
- •active autoimmune disease or medical conditions requiring chronic steroid (i.e., ≥ 20 mg/day prednisone or equivalent) or other immunosuppressive therapy within 28 days prior to the start of treatment
Arms & Interventions
tolododekin alfa (ANK-101) IT Injection in Superficial Lesions
IT injections of ANK-101 once every 3 weeks into superficial lesions
Intervention: tolododekin alfa
tolododekin alfa (ANK-101) IT Injection in Visceral Lesions
IT injections of ANK-101 once every 3 weeks into visceral lesions and every 6 weeks in the expansion
Intervention: tolododekin alfa
tolododekin alfa (ANK-101) IT Injection in Combination with Cemiplimab
IT injections of ANK-101 once every 3 weeks in combination with Cemiplimab into patients with high-risk locally advanced or metastatic CSCC that have superficial lesions
Intervention: tolododekin alfa
tolododekin alfa (ANK-101) IT Injection in Combination with Cemiplimab
IT injections of ANK-101 once every 3 weeks in combination with Cemiplimab into patients with high-risk locally advanced or metastatic CSCC that have superficial lesions
Intervention: Cemiplimab
Outcomes
Primary Outcomes
Incidence and characteristics of DLTs (Parts 1 and 2 only) and TEAEs
Time Frame: From Day 1 to 90 days after last injection of ANK-101
Number and percentage of participants reporting each DLT or TEAE.
RDE of ANK-101
Time Frame: Approximately 12 months
Defined based on the rate of DLTs and TEAEs
Incidence and characteristics of TEAEs of ANK-101 in combination with Cemiplimab according to NCI CTCAE v5.0 (Part 3 only)
Time Frame: From Day 1 to 90 days after last injection of ANK-101 in combination with Cemiplimab.
Number and percentage of participants reporting each TEAE.
Secondary Outcomes
- ORR by RECIST v1.1(Up to 2 years)
- PK: t ½ of IL-12-ABP(Up to 2 years)
- PK: Vss/F of IL-12-ABP(Up to 2 years)
- PK: Cmax of IL-12-ABP(Up to 2 years)
- PK: AUC of IL-12-ABP(Up to 2 years)
- PK: CL/F of IL-12-ABP(Up to 2 years)
- DOR by RECIST v1.1(Up to 2 years)
- PFS by RECIST v1.1(UP to 2 years)
- DCR by RECIST v1.1(Up to 2 years)
- Levels of ADA in serum(Up to 2 years)