High-Risk Skin Cancers With Atezolizumab Plus NT-I7

NCT ID: NCT03901573

Last Updated: 2025-10-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-26
• Study Completion Date: 2023-08-15

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).

Conditions

Melanoma; Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Checkpoint Inhibitor-Naive cSCC, MCC Pts

Anti-PD-1/PD-L1 naïve patients with cSCC and MCC

Group Type: EXPERIMENTAL

NT-I7

Intervention Type: DRUG

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

atezolizumab

Intervention Type: DRUG

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

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

Checkpoint Inhibitor-Relapsed/Refractory cSCC MCC Melanoma Pts

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

Group Type: EXPERIMENTAL

NT-I7

Intervention Type: DRUG

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

atezolizumab

Intervention Type: DRUG

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

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

Interventions

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

Intervention Type: DRUG

atezolizumab

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

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

Intervention Type: DRUG

Other Intervention Names

efineptakin alfa; rhIL-7-hyFc; Tecentriq

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Immune Oncology Network

UNKNOWN

Sponsor Role: collaborator

NeoImmuneTech

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

NgocDiep Le, MD, PhD

Role: STUDY_CHAIR

NeoImmuneTech

Martin Cheever, MD

Role: STUDY_DIRECTOR

Fred Hutchinson Cancer Center

Brian Gastman, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

City of Hope

Duarte, California, United States

Northwestern University

Chicago, Illinois, United States

Dana Farber

Boston, Massachusetts, United States

MGH

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

Mt Sinai

New York, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Providence Portland Medical Center

Portland, Oregon, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Main

View Document

Document Type: Informed Consent Form: Addendum

View Document

Other Identifiers

ION-02

Identifier Type: OTHER

Identifier Source: secondary_id

NIT-106

Identifier Type: -

Identifier Source: org_study_id