Cutaneous Squamous Cell Carcinoma, Melanoma, Merkel Cell Carcinoma
Conditions
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).
Interventions
DRUGNT-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
DRUGatezolizumab
Dose Escalation - atezolizumab IV (intravenous) on Day 1 of each Cycle Dose Expansion - atezolizumab IV (intravenous) on Day 1 of each Cycle
Sponsors
Immune Oncology Network
NeoImmuneTech
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b Baseline characteristics are summarized by dose level (Phase 1b: 120, 360, 840, 1200 μg/kg; Phase 2a: 1200 μg/kg) rather than by Arm because pooling was pre-specified in the Statistical Analysis Plan (Section 4.2.1) and protocol. Efficacy analyses also pool Phase 1b doses (120-840 μg/kg) and Phase 2a 1200 μg/kg dose. This approach reflects study design and planned analyses. | 16 |
| Phase 2a Baseline characteristics are summarized by dose level (Phase 1b: 120, 360, 840, 1200 μg/kg; Phase 2a: 1200 μg/kg) rather than by Arm because pooling was pre-specified in the Statistical Analysis Plan (Section 4.2.1) and protocol. Efficacy analyses also pool Phase 1b doses (120-840 μg/kg) and Phase 2a 1200 μg/kg dose. This approach reflects study design and planned analyses. | 15 |
| Total | 31 |
Baseline characteristics
| Characteristic | Phase 1b | Phase 2a | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 11 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 4 Participants | 11 Participants |
| Age, Continuous | 65.4 years | 65.7 years | 65.58 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 13 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 11 Participants | 12 Participants | 23 Participants |
| Region of Enrollment United States | 16 participants | 15 participants | 31 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
| Weight | 81.42 kg | 78.00 kg | 79.71 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 3 / 3 | 5 / 7 | 1 / 3 | 8 / 15 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 7 / 7 | 3 / 3 | 14 / 15 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 5 / 7 | 1 / 3 | 9 / 15 |
Outcome results
Primary
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. 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.
Time frame: 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)
Population: Safety: All patients who receive at least 1 dose of the investigational regimen ; DLT: All patients who receive at least 1 dose of the investigational regimen and complete the full 3-week DLT window or who do not complete the full 3-week DLT window due to the occurrence of a DLT.; Analyses of adverse events will be performed for those events that are considered treatment emergent.(Subjects with one or more AEs within a level of MedDRA are counted only once in that level)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b-Dose Level 1 | 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 | Patient Incidence of Adverse Events of Special Interest | 2 Participants |
| Phase 1b-Dose Level 1 | 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 | Incidence of Treatment-Related TEAE | 3 Participants |
| Phase 1b-Dose Level 1 | 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 | Experienced a DLT | 0 Participants |
| Phase 1b-Dose Level 1 | 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 | Patient Incidence of Serious Treatment-Emergent Adverse Events | 1 Participants |
| Phase 1b-Dose Level 1 | 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 | Patient Incidence of Serious Treatment-Related Adverse Events | 0 Participants |
| Phase 1b-Dose Level 2 | 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 | Patient Incidence of Adverse Events of Special Interest | 1 Participants |
| Phase 1b-Dose Level 2 | 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 | Patient Incidence of Serious Treatment-Related Adverse Events | 0 Participants |
| Phase 1b-Dose Level 2 | 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 | Patient Incidence of Serious Treatment-Emergent Adverse Events | 0 Participants |
| Phase 1b-Dose Level 2 | 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 | Experienced a DLT | 0 Participants |
| Phase 1b-Dose Level 2 | 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 | Incidence of Treatment-Related TEAE | 3 Participants |
| Phase 1b-Dose Level 3 | 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 | Patient Incidence of Serious Treatment-Related Adverse Events | 3 Participants |
| Phase 1b-Dose Level 3 | 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 | Incidence of Treatment-Related TEAE | 7 Participants |
| Phase 1b-Dose Level 3 | 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 | Patient Incidence of Serious Treatment-Emergent Adverse Events | 5 Participants |
| Phase 1b-Dose Level 3 | 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 | Patient Incidence of Adverse Events of Special Interest | 3 Participants |
| Phase 1b-Dose Level 3 | 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 | Experienced a DLT | 1 Participants |
| Phase 1b-Dose Level 4 | 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 | Experienced a DLT | 0 Participants |
| Phase 1b-Dose Level 4 | 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 | Incidence of Treatment-Related TEAE | 3 Participants |
| Phase 1b-Dose Level 4 | 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 | Patient Incidence of Adverse Events of Special Interest | 0 Participants |
| Phase 1b-Dose Level 4 | 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 | Patient Incidence of Serious Treatment-Related Adverse Events | 0 Participants |
| Phase 1b-Dose Level 4 | 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 | Patient Incidence of Serious Treatment-Emergent Adverse Events | 1 Participants |
| Phase 2- | 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 | Patient Incidence of Serious Treatment-Related Adverse Events | 4 Participants |
| Phase 2- | 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 | Patient Incidence of Adverse Events of Special Interest | 9 Participants |
| Phase 2- | 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 | Incidence of Treatment-Related TEAE | 14 Participants |
| Phase 2- | 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 | Experienced a DLT | 0 Participants |
| Phase 2- | 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 | Patient Incidence of Serious Treatment-Emergent Adverse Events | 9 Participants |
Primary
Phase 2a: To Evaluate the Objective Response Rate (ORR) According to RECIST 1.1 and iRECIST, as Determined by the Investigator
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).
Time frame: 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
Population: The Arm/Group has been categorized based on the dosing regimen of NT-I7 per study design: Phase 1b, DL1-3 every 3 weeks (Q3W); Phase 1b DL4 and Phase 2a, Q6W.treatment and have at least one evaluable post baseline tumor assessment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b-Dose Level 1 | Phase 2a: To Evaluate the Objective Response Rate (ORR) According to RECIST 1.1 and iRECIST, as Determined by the Investigator | Complete response | 0 Participants |
| Phase 1b-Dose Level 1 | Phase 2a: To Evaluate the Objective Response Rate (ORR) According to RECIST 1.1 and iRECIST, as Determined by the Investigator | Partial response | 0 Participants |
| Phase 1b-Dose Level 1 | Phase 2a: To Evaluate the Objective Response Rate (ORR) According to RECIST 1.1 and iRECIST, as Determined by the Investigator | Stable disease | 9 Participants |
| Phase 1b-Dose Level 1 | Phase 2a: To Evaluate the Objective Response Rate (ORR) According to RECIST 1.1 and iRECIST, as Determined by the Investigator | Progressive disease | 3 Participants |
| Phase 1b-Dose Level 2 | Phase 2a: To Evaluate the Objective Response Rate (ORR) According to RECIST 1.1 and iRECIST, as Determined by the Investigator | Progressive disease | 7 Participants |
| Phase 1b-Dose Level 2 | Phase 2a: To Evaluate the Objective Response Rate (ORR) According to RECIST 1.1 and iRECIST, as Determined by the Investigator | Complete response | 0 Participants |
| Phase 1b-Dose Level 2 | Phase 2a: To Evaluate the Objective Response Rate (ORR) According to RECIST 1.1 and iRECIST, as Determined by the Investigator | Stable disease | 6 Participants |
| Phase 1b-Dose Level 2 | Phase 2a: To Evaluate the Objective Response Rate (ORR) According to RECIST 1.1 and iRECIST, as Determined by the Investigator | Partial response | 2 Participants |
Secondary
To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab
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.
Time frame: C1D1 through end of 90-day follow-up
Population: All patients who receive at least 1 dose of the investigational regimen.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | n (Missing) | 0 Participants |
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | n (Missing) | 1 Participants |
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | Subjects that are ADA Positive | 0 Participants |
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | Subjects that are ADA Negative | 0 Participants |
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | n (Missing) | 0 Participants |
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | Subjects that are ADA Negative | 0 Participants |
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | Subjects that are ADA Positive | 2 Participants |
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | n (Missing) | 0 Participants |
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | Subjects that are ADA Positive | 3 Participants |
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | Subjects that are ADA Negative | 0 Participants |
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | Subjects that are ADA Negative | 3 Participants |
| Phase 1b-Dose Level 1 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | Subjects that are ADA Positive | 3 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | Subjects that are ADA Negative | 0 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | n (Missing) | 0 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | Subjects that are ADA Negative | 3 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | Subjects that are ADA Negative | 0 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | Subjects that are ADA Positive | 0 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | n (Missing) | 1 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | n (Missing) | 0 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | n (Missing) | 1 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | Subjects that are ADA Positive | 2 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | Subjects that are ADA Negative | 1 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | Subjects that are ADA Positive | 2 Participants |
| Phase 1b-Dose Level 2 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | Subjects that are ADA Positive | 2 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | n (Missing) | 3 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | Subjects that are ADA Positive | 0 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | Subjects that are ADA Negative | 7 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | n (Missing) | 0 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | Subjects that are ADA Negative | 4 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | Subjects that are ADA Positive | 2 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | n (Missing) | 1 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | Subjects that are ADA Negative | 0 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | n (Missing) | 0 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | Subjects that are ADA Positive | 7 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | Subjects that are ADA Positive | 4 Participants |
| Phase 1b-Dose Level 3 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | Subjects that are ADA Negative | 0 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | n (Missing) | 0 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | Subjects that are ADA Positive | 0 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | n (Missing) | 0 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | Subjects that are ADA Positive | 3 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | Subjects that are ADA Positive | 3 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | Subjects that are ADA Negative | 0 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | Subjects that are ADA Negative | 0 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | Subjects that are ADA Positive | 3 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | n (Missing) | 0 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | Subjects that are ADA Negative | 3 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | n (Missing) | 0 Participants |
| Phase 1b-Dose Level 4 | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | Subjects that are ADA Negative | 0 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | n (Missing) | 2 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | Subjects that are ADA Positive | 4 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | Subjects that are ADA Positive | 1 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | n (Missing) | 6 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | Subjects that are ADA Negative | 12 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | Subjects that are ADA Negative | 2 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | Subjects that are ADA Negative | 0 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | C2D1 | Subjects that are ADA Positive | 11 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | Subjects that are ADA Positive | 9 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | End of Treatment | Subjects that are ADA Negative | 0 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | Baseline | n (Missing) | 2 Participants |
| Phase 2- | To Evaluate Immunogenicity of NT-I7 in Combination With Atezolizumab | 90-Day Follow up | n (Missing) | 11 Participants |
Secondary
To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab
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.
Time frame: 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
Population: Defined as the time from the first occurrence of stable disease or better (PR or CR or SD) to the time of the first documented disease progression or death from any cause, whichever occurs first per RECIST v1.1. The Arm/Group has been categorized based on the dosing regimen of NT-I7 per study design: Phase 1b, DL1-3 every 3 weeks (Q3W); Phase 1b DL4 and Phase 2a, Q6W.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1b-Dose Level 1 | To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab | Duration of stable disease | 2.2 Months |
| Phase 1b-Dose Level 1 | To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab | Progression -Free Survival, RECIST 1.1 | 4.2 Months |
| Phase 1b-Dose Level 1 | To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab | Overall Survival | 11.1 Months |
| Phase 1b-Dose Level 2 | To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab | Duration of stable disease | 2.0 Months |
| Phase 1b-Dose Level 2 | To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab | Progression -Free Survival, RECIST 1.1 | 3.5 Months |
| Phase 1b-Dose Level 2 | To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab | Overall Survival | NA Months |
Secondary
To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab (DCR)
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.
Time frame: 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
Population: All patients who received at least one cycle of study treatment and have at least one evaluable post baseline tumor assessment. The Arm/Group has been categorized based on the dosing regimen of NT-I7 per study design: Phase 1b, DL1-3 every 3 weeks (Q3W); Phase 1b DL4 and Phase 2a, Q6W.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-Dose Level 1 | To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab (DCR) | 75.0 percentage of participants |
| Phase 1b-Dose Level 2 | To Make a Preliminary Assessment of the Anti-tumor Activity of NT-I7 in Combination With Atezolizumab (DCR) | 53.3 percentage of participants |