NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

Ovarian Cancer Clinical Trial

Official title:

An Open-label Phase 1b/2a Study of NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04332653
• Other study ID #: NIT-110
• Secondary ID: MK-3475-A60KEYNO
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 10, 2020
• Est. completion date: March 31, 2025

Study information

• Verified date: March 2024
• Source: NeoImmuneTech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purposes of Phase 1b of this study are to determine the following in participants with advanced solid tumors:

• Safety and tolerability of NT-I7 in combination with pembrolizumab

• Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D)

The main purpose of Phase 2a of this study is to assess the preliminary anti-tumor activity of NT-I7 in combination with pembrolizumab in participants with checkpoint inhibitor (CPI) treated and naïve relapsed and refractory (R/R) tumors.

The main purpose of the Biomarker Cohort is to assess a potential correlation between tumor infiltrating lymphocytes (TILs) and clinical benefits in participants with CPI-naïve R/R ovarian cancer (OC).

Description:

This is a multicenter, open-label Phase 1b/2a study of NT-I7 in combination with pembrolizumab. The study consists of a dose escalation phase (Phase 1b) followed by a dose expansion phase (Phase 2a) and a Biomarker Cohort.

The Phase 1b is designed to assess the safety and tolerability, including determination of the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of NT-I7.

The main purpose of Phase 2a of this study is to assess the preliminary antitumor activity of NT-I7 in combination with pembrolizumab in participants with relapsed/refractory

• checkpoint inhibitor (CPI)-treated Triple Negative Breast Cancer (TNBC), Non-small Cell Lung Cancer (NSCLC), and Small Cell Lung Cancer (SCLC)

• checkpoint inhibitor (CPI)-naïve Microsatellite Stable Colorectal Cancer (MSS-CRC), and Pancreatic Cancer (PC) The Biomarker Cohort is designed to assess the correlation between tumor infiltrating lymphocytes (TILs) and clinical benefits of NT-I7 in combination with pembrolizumab in participants with CPI naïve R/R Ovarian Cancer (OC).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 215
• Est. completion date: March 31, 2025
• Est. primary completion date: November 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

(Participants must meet all the following to be eligible)

• Participants with histologically or cytologically confirmed advanced or metastatic solid tumors.

• Have measurable disease per RECIST v1.1.

• Participants enrolling in the Phase 1b, Arms I, IV, IVa, V, and Va of the Phase 2a, and the Biomarker Cohort OC must have biopsiable disease.

• Female participants who are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks; female participants of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or to use dual methods of contraception for the duration of study treatment and for 120 days after the last dose of study treatment (pembrolizumab and/or NT-I7).

• Non-sterile male participants who are sexually active with female partners of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or to use highly effective method(s) of contraception for the duration of study treatment and for 120 days after the last dose of study treatment (pembrolizumab and/or NT-I7).

• Meet the requirements for the intended stages and arms (disease specific inclusion criteria), as follows:

Applicable to the Dose escalation phase (Phase 1b) only: (Biopsy Arm)

• Relapsed/refractory advanced solid tumors.

Applicable to the Dose expansion phase (Phase 2a) only:

Anti-PD-1/anti-PD-L1 refractory criteria for CPI-treated TNBC, NSCLC, and SCLC

• Has received at least 2 doses of an approved anti-PD-1/anti-PD-L1 monoclonal antibody (mAb).

• Has demonstrated disease progression after anti-PD-1/anti-PD-L1.

Specific to Arm I: CPI-treated R/R TNBC (Biopsy Arm)

• Histopathologic or cytologic documented TNBC.

• Received one or more prior therapies for TNBC in the advanced or metastatic setting, and prior treatment (for advanced, metastatic or (neo) adjuvant).

Specific to Arm II: CPI-treated R/R NSCLC

• Had prior treatment with CPI. Participants with estimated glomerular filtration rate (EGFR), BRAF, or c-ros oncogene 1(ROS1) mutations or anaplastic lymphoma kinase (ALK) translocations are required to have received prior therapy with the appropriate tyrosine kinase inhibitor (TKI).

Specific to Arm III: CPI-treated R/R SCLC

• Recurrent extensive-stage SCLC; Received prior CPI therapy.

Specific to Arm IV and IVa: CPI-naïve R/R MSS-CRC (Biopsy Arm)

• MSS-CRC (categorized as MSS by immunohistochemistry(IHC) or polymerase chain reaction (PCR).

• Previously treated with standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan; participants treated with CPI are not eligible.

Specific to Arm V and Va: CPI-naïve R/R Pancreatic Cancer (Biopsy Arm)

• Have documented radiographic progression to or documented in tolerance of first line systemic chemotherapy which included either gemcitabine or Fluorouracil (5-FU)-based regimen (including capecitabine); participants treated previously with CPI are not eligible.

Specific to Biomarker Cohort: CPI-naïve R/R Ovarian Cancer

• Up to 5 prior lines of treatment, including platinum-based treatment(s); participants treated previously with CPIs are not eligible.

• Willing to provide pre- and on-treatment tumor biopsies.

Exclusion Criteria:

• Pregnant, lactating or breastfeeding.

• Receiving chemotherapy or any anti-cancer therapy (approved or investigational) with half-life <1 week within 30 days or 5 half-lives.

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate if stable.

• Participants who have received treatment with systemic immunosuppressive medications.

• Has a history of non-infectious pneumonitis that required steroids or current pneumonitis.

• Has had an allogenic tissue/solid organ transplant or bone marrow transplant.

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137) and was discontinued from that treatment due to a Grade 3 or higher Immune related adverse event (irAE).

Related Conditions & MeSH terms

• Any Advanced Solid Tumors
• Lung Neoplasms
• Microsatellite Stable Colorectal Cancer
• Non Small Cell Lung Cancer
• Ovarian Cancer
• Pancreatic Cancer
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• NT-I7
Administered by intramuscular (IM) injection
• pembrolizumab (KEYTRUDA®)
Administered by intravenous (IV) injection

Locations

Country	Name	City	State
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri
United States	Moffit Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
NeoImmuneTech	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b: Safety and Tolerability of NT-I7 in Combination With Pembrolizumab to Determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of NT-I7	Incidence, nature and severity of Adverse Events (AEs) graded according to NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0; Incidence and nature of Dose-Limiting Toxicities (DLTs)	Up to 2 years
Primary	Phase 1b: Safety and Tolerability of NT-I7 in Combination With Pembrolizumab to Determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of NT-I7	Statistical correlation of dose levels with safety and efficacy parameters.	Up to 2 years
Primary	Phase 2a: Preliminary Assessment of the Objective Response Rate (ORR) of NT-I7 in Combination with Pembrolizumab		Up to 2 years
Primary	Biomarker Cohort: Number of Tumor-Infiltrating Lymphocytes (TILs)		Up to 2 years
Primary	Biomarker Cohort: Distribution of Tumor-Infiltrating Lymphocytes (TILs)	TILs in tumor biopsy samples will be identified using a multi-spectral Immunofluorescence (IF) assay.	Up to 2 years
Primary	Biomarker Cohort: Phenotype of Tumor-Infiltrating Lymphocytes (TILs)	TILs in tumor biopsy samples will be identified using a multi-spectral Immunofluorescence (IF) assay.	Up to 2 years
Secondary	Duration of Objective Response (DOR)		Up to 2 years
Secondary	Disease Control Rate (DCR)		Up to 2 years
Secondary	Progression Free Survival (PFS)		Up to 2 years
Secondary	Overall Survival (OS)		Up to 2 years
Secondary	Number of Participants Who Experience an Increase in Anti-Drug Antibodies (ADAs) to NT-I7		Up to 2 years
Secondary	Biomarker Cohort: Objective Response Rate (ORR)		Up to 2 years
Secondary	Incidence, Nature, and Severity of Adverse Events (AEs) graded according to National Cancer Institute Common Terminologies Criteria for Adverse Events (NCI CTCAE) v5.0		Up to 2 years