High-Risk Skin Cancers With Atezolizumab Plus NT-I7

Phase 1

Terminated

• Conditions: Melanoma; Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma
• Interventions: Drug: NT-I7; Drug: atezolizumab

• Registration Number: NCT03901573
• Lead Sponsor: NeoImmuneTech

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 Timeline

• Study First Submitted: 2019-03-26
• Study First Submitted QC: 2019-04-01
• Study First Posted: 2019-04-03
• Study Start: 2019-12-26
• Primary Completion: 2023-08-15
• Study Completion: 2023-08-15
• Results First Submitted: 2024-08-15
• Status Verified: 2025-10
• Results First Submitted QC: 2025-10-06
• Last Update Submitted: 2025-10-06
• Results First Posted: 2025-10-22
• Last Update Posted: 2025-10-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 31

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Checkpoint Inhibitor-Relapsed/Refractory cSCC MCC Melanoma Pts	atezolizumab	Anti-PD-1/PD-L1 relapsed/refractory patients with cSCC, MCC and melanoma
Checkpoint Inhibitor-Relapsed/Refractory cSCC MCC Melanoma Pts	NT-I7	Anti-PD-1/PD-L1 relapsed/refractory patients with cSCC, MCC and melanoma
Checkpoint Inhibitor-Naive cSCC, MCC Pts	atezolizumab	Anti-PD-1/PD-L1 naïve patients with cSCC and MCC
Checkpoint Inhibitor-Naive cSCC, MCC Pts	NT-I7	Anti-PD-1/PD-L1 naïve patients with cSCC and MCC

Primary Outcome Measures

Name	Time	Method
Phase 1b: To Evaluate the Safety and Tolerability of NT-I7 in Combination With Atezolizumab, Including Estimation of the Maximum Tolerated Dose and/or the Recommended Phase 2 Dose	1. On or after administration of study treatment through 30 days after the last dose of study treatment (approximately 25 months after enrollment) 2.First 21 days (C1/D1 through Day 21)	1. Incidence, nature, and severity of adverse events graded according to NCI CTCAE 5.0; 2. Incidence and nature of dose-limiting toxicities (DLTs); Note: ORR (Defined as the percentage of patients who have at least one confirmed partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1). ORR is included in Phase 2a Primary Outcome Measure.
Phase 2a: To Evaluate the Objective Response Rate (ORR) According to RECIST 1.1 and iRECIST, as Determined by the Investigator	C1D1 until the start of a new anticancer treatment, disease progression, pregnancy, death, withdrawal of consent or end of study, whichever occurs first, up to 1 year	Pooling of dose levels for this Outcome Measure was pre-specified in the Statistical Analysis Plan (SAP Section 4.2.1) and the study protocol. Phase 1b dose-escalation results are summarized by dose level (120, 360, 840, 1200 µg/kg), and Phase 2a results under 1200 µg/kg. Efficacy analyses pool Phase 1b doses (120-840 µg/kg) and the Phase 2a 1200 µg/kg dose to reflect the predefined analysis strategy and study objectives. This approach was chosen due to small sample sizes and early study termination, as documented in the Clinical Study Report (CSR).

Secondary Outcome Measures

Name	Time	Method
To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab	C1D1 through end of 90-day follow-up	The ADA status will be defined using the baseline and postbaseline results. Anti-drug antibody negative is defined as negative results at all time points. Anti-drug antibody positive is defined as a positive result at any time point, including baseline.
To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab (DCR)	C1D1 until the start of a new anticancer treatment, disease progression, pregnancy, death, withdrawal of consent or end of study, whichever occurs first, up to 1 year	For Outcome Measure 4 and 5, pooling was also pre-specified in SAP Section 4.8 and CSR Section 11.4. Kaplan-Meier analyses were conducted on pooled groups for interpretability and statistical validity. Separate reporting by Arm was not feasible due to small sample sizes and early termination.
To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab	C1D1 until the start of a new anticancer treatment, disease progression, pregnancy, death, withdrawal of consent or end of study, whichever occurs first, up to 1 year	Pooling of dose levels for this Outcome Measure was also pre-specified in the SAP and study protocol to maintain consistency across efficacy endpoints. For this Outcome Measure (e.g., Disease Control Rate), pooled groups were defined as Phase 1b (120-840 µg/kg) and Phase 2a (1200 µg/kg). This approach aligns with the predefined analyses and study objectives and prevents misleading subgroup estimates given the limited enrollment and early study termination.

Trial Locations

Locations (8)

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