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).
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.
