High-Risk Skin Cancers With Atezolizumab Plus NT-I7

• ClinicalTrials.gov Identifier: NCT03901573
• Recruitment Status: Terminated
• First Posted: April 3, 2019
• Last Update Posted: February 22, 2024
• Sponsor: NeoImmuneTech
• Collaborator: Immune Oncology Network
• Information provided by (Responsible Party): NeoImmuneTech

Tracking Information

• First Submitted Date: March 26, 2019
• First Posted Date: April 3, 2019
• Last Update Posted Date: February 22, 2024
• Actual Study Start Date: December 26, 2019
• Actual Primary Completion Date: August 15, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 3, 2019)

Safety and Tolerability of NT-I7 in combination with atezolizumab to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of NT-I7 [ Time Frame: Up to approximately 56 months ]

• Incidence, nature, and severity of adverse events graded according to NCI CTCAE v5.0
• Incidence and nature of Dose-Limiting Toxicities (DLTs)
• Potential correlation with PK, pharmacodynamic, safety, and efficacy parameters

Original Primary Outcome Measures (submitted: April 1, 2019)

Safety and Tolerability of NT-I7 in combination with atezolizumab [ Time Frame: Up to approximately 56 months ]

Safety and Tolerability of NT-I7 in combination with atezolizumab including estimation of the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D)

Current Secondary Outcome Measures (submitted: April 3, 2019)

• To evaluate immunogenicity of NT-I7 and atezolizumab [ Time Frame: Up to approximately 56 months ]
  To determine and evaluate the incidence of anti-drug antibodies (ADA) to NT-I7 and atezolizumab during the study relative to the prevalence of ADA at baseline
• Preliminary assessment of the Objective Response Rate (ORR) of NT-I7 in combination with atezolizumab [ Time Frame: Up to approximately 56 months ]
  To preliminarily assess the Objective Response Rate (ORR) defined as percentage of patients who have at least one confirmed partial response (PR) or complete response (CR) according to RECIST v1.1, as determined by the investigator.
• Preliminary assessment the Disease Control Rate (DCR) of NT-I7 in combination with atezolizumab [ Time Frame: Up to approximately 56 months ]
  To preliminarily assess the Disease Control Rate (DCR) defined as proportion of patients with a best overall response of CR, PR or stable disease (SD).
• Preliminary assessment the Duration of Objective Response (DOR) of NT-I7 in combination with atezolizumab [ Time Frame: Up to approximately 56 months ]
  To preliminarily assess the Duration of Objective Response (DOR), defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, per RECIST v1.1 as determined by the investigator.
• Preliminary assessment the Progression Free Survival (PFS) of NT-I7 in combination with atezolizumab [ Time Frame: Up to approximately 56 months ]
  To preliminarily assess the Progression Free Survival (PFS), defined as the time from the first study treatment (Cycle 1 Day 1) to the first occurrence of progression or death from any cause, whichever occurs first, per RECIST v1.1 as determined by the investigator.
• Preliminary assessment the Overall Survival (OS) of NT-I7 in combination with atezolizumab [ Time Frame: Up to approximately 56 months ]
  To preliminarily assess the Overall Survival (OS) defined as the time from first study treatment (Cycle 1 Day 1) to death from any cause.

Original Secondary Outcome Measures (submitted: April 1, 2019)

• To evaluate immunogenicity of NT-I7 and atezolizumab [ Time Frame: Up to approximately 56 months ]
  To evaluate immunogenicity of NT-I7 and atezolizumab when administered in combination
• Preliminary assessment of the Objective Response Rate (ORR) of NT-I7 in combination with atezolizumab [ Time Frame: Up to approximately 56 months ]
  To preliminarily assess the Objective Response Rate (ORR) defined as percentage of patients who have at least one confirmed partial response (PR) or complete response (CR) according to RECIST v1.1, as determined by the investigator.
• Preliminary assessment the Disease Control Rate (DCR) of NT-I7 in combination with atezolizumab [ Time Frame: Up to approximately 56 months ]
  To preliminarily assess the Disease Control Rate (DCR) defined as proportion of patients with a best overall response of CR, PR or stable disease (SD)percentage of patients who have at least one confirmed partial response (PR) or complete response (CR) according to RECIST v1.1, as determined by the investigator.
• Preliminary assessment the Duration of Objective Response (DOR) of NT-I7 in combination with atezolizumab [ Time Frame: Up to approximately 56 months ]
  To preliminarily assess the Duration of Objective Response (DOR), defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, per RECIST v1.1 as determined by the investigator.
• Preliminary assessment the Progression Free Survival (PFS) of NT-I7 in combination with atezolizumab [ Time Frame: Up to approximately 56 months ]
  To preliminarily assess the Progression Free Survival (PFS), defined as the time from the first study treatment (Cycle 1 Day 1) to the first occurrence of progression or death from any cause, whichever occurs first, per RECIST v1.1 as determined by the investigator.
• Preliminary assessment the Overall Survival (OS) of NT-I7 in combination with atezolizumab [ Time Frame: Up to approximately 56 months ]
  To preliminarily assess the Overall Survival (OS) defined as the time from first study treatment (Cycle 1 Day 1) to death from any cause.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: High-Risk Skin Cancers With Atezolizumab Plus NT-I7
• Official Title: A Phase 1b/2a, Open Label Study to Evaluate Anti-tumor Efficacy and Safety of rhIL-7-hyFc (NT-I7) in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Anti-PD-1/PD-L1 naïve or Relapsed/Refractory High-risk Skin Cancers
• Brief Summary: The purpose of this study is to test whether the addition of NT-I7 to atezolizumab provides clinically meaningful outcomes for patients with anti-PD-1/PD-L1 naive or relapsed/refractory high-risk melanoma, Merkel Cell Carcinoma (MCC) and cutaneous Squamous Cell Carcinoma (cSCC)

Detailed Description

This is a Phase 1b/2a, open-label, multicenter study to evaluate the safety, tolerability and anti-tumor effect of NT-I7 (rhIL-7-hyFc) in combination with atezolizumab (MPDL3280A, anti-PD-L1) in patients with anti-PD-1/PD-L1 naïve or relapsed/refractory high-risk skin cancers including cutaneous Squamous Cell Carcinoma (cSCC), Merkel Cell Carcinoma (MCC) and melanoma.

This study has been designed to evaluate the safety and tolerability, including the Maximum Tolerated Dose (MTD) or recommended Phase 2 dose (RP2D), of NT-I7 in combination with atezolizumab.

There are two phases to this study:

• Phase 1b, a NT-I7 dose-escalation phase to determine the MTD or RP2D
• Phase 2a, a non-randomized parallel dose expansion phase to confirm the MTD or RP2D in both arms.

Arm I: Anti-PD-1/PD-L1 (checkpoint inhibitors, CPI) naïve patients with cSCC and MCC

Arm II: Anti-PD-1/PD-L1 relapsed/refractory patients with cSCC, MCC and melanoma

Number of Patients A total of up to 84 patients will be enrolled; Up to 24 patients will be enrolled in the Phase 1b (up to 6 patients per dose level, using 3 + 3 design), and 60 patients will be enrolled in the Phase 2a (24 patients in Arm I, i.e., 12 patients for each indication, and 36 in Arm II, i.e., 12 patients for each indication).

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Melanoma
• Merkel Cell Carcinoma
• Cutaneous Squamous Cell Carcinoma

Intervention

• Drug: NT-I7

  Dose Escalation (Phase 1b) - NT-I7 IM (intramuscular) on Day 1 of each Cycle until MTD or RP2D is achieved.

  Dose Expansion - NT-I7 IM (intramuscular) on Day 1 of each Cycle, at Maximum Tolerated Dose (MTD) or RP2D defined in escalation phase

  Other Names:

  • efineptakin alfa
  • rhIL-7-hyFc
• Drug: atezolizumab

  Dose Escalation - atezolizumab IV (intravenous) on Day 1 of each Cycle

  Dose Expansion - atezolizumab IV (intravenous) on Day 1 of each Cycle

  Other Name: Tecentriq

Study Arms

• Experimental: Checkpoint Inhibitor-Naive cSCC, MCC Pts
  Anti-PD-1/PD-L1 naïve patients with cSCC and MCC
  Interventions:

  • Drug: NT-I7
  • Drug: atezolizumab
• Experimental: Checkpoint Inhibitor-Relapsed/Refractory cSCC MCC Melanoma Pts
  Anti-PD-1/PD-L1 relapsed/refractory patients with cSCC, MCC and melanoma
  Interventions:

  • Drug: NT-I7
  • Drug: atezolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 20, 2024): 31
• Original Estimated Enrollment (submitted: April 1, 2019): 84
• Actual Study Completion Date: August 15, 2023
• Actual Primary Completion Date: August 15, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Patients must be ≥18 years of age on day of signing informed consent document.
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%).
3. Patients must have adequate organ and marrow function.
4. Patients positive for HIV can be considered.
5. Arm I - cSCC: Patients must have biopsy-proven metastatic cSCC or locoregional cSCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy; MCC: Patients must have biopsy-proven metastatic MCC or locoregional MCC in need of systemic therapy, including patients that have not had prior systemic therapy or have recurred following standard locoregional therapy with surgery and/or radiation therapy. Prior chemotherapy is allowed.
6. Arm II - MCC: Patients must have biopsy-proven metastatic MCC or locoregional MCC that has recurred following anti-PD-1 or anti-PD-L1, or has SD following anti-PD-1 or anti-PD-L1, defined as 12 weeks of SD per RECIST 1.1; cSCC: Patients must have biopsy-proven metastatic cSCC or locoregional cSCC that has recurred following anti-PD-1 or anti-PD-L1, or has SD following anti-PD-1 or anti-PD-L1, defined as 12 weeks of SD per RECIST 1.1; Melanoma: Patients must have biopsy-proven metastatic melanoma or locoregional melanoma that has recurred following anti-PD-1, anti-PD-L1, or has SD following anti-PD-1 or anti-PD-L1, defined as 12 weeks of SD per RECIST 1.1.

Note: Prior therapy with ipilimumab is allowed (subject to a 6-week washout period) but not required.

Note: Progression following targeted therapies (e.g., BRAF inhibitor and/or MEK inhibitor) or other approved (e.g., talimogene laherparepvec [T-VEC]) or investigational therapies is allowed.

Key Exclusion Criteria:

1. Pregnancy, lactation, or breastfeeding.
2. Significant cardiovascular disease.
3. Poorly controlled Type 2 diabetes mellitus.
4. Major surgical procedure, other than for diagnosis, within 28 days prior to Cycle 1, Day 1, or anticipation of need for a major surgical procedure during the study.
5. Patients who have had chemotherapy or radiotherapy within 2 weeks (4 weeks for nitrosoureas or systemic mitomycin C) prior to Cycle 1, Day 1.
6. Patients who had prior treatment with immune CPIs, immunomodulatory monoclonal antibodies (mAbs), and/or mAb-derived therapies within 6 weeks before the initiation of study treatment, except for prior anti-PD-L1/anti-PD-1, which requires a 3-week washout period.
7. Patients who have received treatment with any other investigational agent within 4 weeks prior to Cycle 1, Day 1.
8. Patients who have received treatment and failed therapy with checkpoint inhibition plus a T-cell growth factor, e.g., IL-2 (NTKR-204), IL-15 (ALT-803) or IL-7 (CYT107).
9. Patients with known primary central nervous system (CNS) malignancy, untreated CNS metastases, or active CNS metastases (progressing or requiring corticosteroids for symptomatic control) are excluded, with some exceptions.
10. Patients who have leptomeningeal disease.
11. Patients with autoimmune disease history.
12. Patients who have received treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1.
13. Patients who have a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
14. Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening).
15. Patients with active tuberculosis (TB).
16. Patients who have severe infections within 4 weeks prior to Cycle 1, Day 1.
17. Patients who have signs or symptoms of recent infection (not meeting the above criteria for severe infections) within 2 weeks before initiation of study treatment.
18. Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation.
19. Patients who have received a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipate that such a live attenuated vaccine be required during the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03901573
• Other Study ID Numbers: NIT-106; ION-02 ( Other Identifier: Immune Oncology Network )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: NeoImmuneTech
• Original Responsible Party: Same as current
• Current Study Sponsor: NeoImmuneTech
• Original Study Sponsor: Same as current
• Collaborators: Immune Oncology Network

Investigators

• Study Chair: NgocDiep Le, MD, PhD; NeoImmuneTech, Inc.
• Study Director: Martin Cheever, MD; Fred Hutchinson Cancer Center
• Principal Investigator: Brian Gastman, MD; The Cleveland Clinic

• PRS Account: NeoImmuneTech
• Verification Date: February 2024