Clinical Trials /

High-Risk Skin Cancers With Atezolizumab Plus NT-I7

NCT03901573

Description:

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)

Related Conditions:
  • Melanoma
  • Merkel Cell Carcinoma
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: NIT-106
  • SECONDARY ID: ION-02
  • NCT ID: NCT03901573

Conditions

  • Melanoma
  • Merkel Cell Carcinoma
  • Cutaneous Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
NT-I7Hyleukin-7, rhIL-7-hyFcCheckpoint Inhibitor-Naive cSCC, MCC Pts
atezolizumabTecentriqCheckpoint Inhibitor-Naive cSCC, MCC Pts

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Checkpoint Inhibitor-Naive cSCC, MCC PtsExperimentalAnti-PD-1/PD-L1 naïve patients with cSCC and MCC
  • NT-I7
  • atezolizumab
Checkpoint Inhibitor-Relapsed/Refractory cSCC MCC Melanoma PtsExperimentalAnti-PD-1/PD-L1 relapsed/refractory patients with cSCC, MCC and melanoma
  • NT-I7
  • atezolizumab

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:To evaluate immunogenicity of NT-I7 and atezolizumab
Time Frame:Up to approximately 56 months
Safety Issue:
Description: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
Measure:Preliminary assessment of the Objective Response Rate (ORR) of NT-I7 in combination with atezolizumab
Time Frame:Up to approximately 56 months
Safety Issue:
Description: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.
Measure:Preliminary assessment the Disease Control Rate (DCR) of NT-I7 in combination with atezolizumab
Time Frame:Up to approximately 56 months
Safety Issue:
Description: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).
Measure:Preliminary assessment the Duration of Objective Response (DOR) of NT-I7 in combination with atezolizumab
Time Frame:Up to approximately 56 months
Safety Issue:
Description: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.
Measure:Preliminary assessment the Progression Free Survival (PFS) of NT-I7 in combination with atezolizumab
Time Frame:Up to approximately 56 months
Safety Issue:
Description: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.
Measure:Preliminary assessment the Overall Survival (OS) of NT-I7 in combination with atezolizumab
Time Frame:Up to approximately 56 months
Safety Issue:
Description:To preliminarily assess the Overall Survival (OS) defined as the time from first study treatment (Cycle 1 Day 1) to death from any cause.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NeoImmuneTech

Last Updated

February 5, 2020