A Phase 1b/2, Open-Label, Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab for Participants with Advanced Unresectable And/or Metastatic Immune Checkpoint Inhibitor (ICI) Refractory Solid Tumors or ICI Naïve MSS/MSI-Low Solid Tumors

NextCure, Inc.17 sites in 1 country97 target enrollmentOctober 6, 2022

ConditionsAdvanced or Metastatic Solid Tumors Microsatellite Instability Low Microsatellite Instability High Microsatellite Stable Ovarian Cancer Gastric Cancer Colo-rectal Cancer Esophageal Cancer Endometrial Cancer Head Neck Cancer Cervical Cancer Lung Cancer

InterventionsNC410 pembrolizumab

DrugsNC410 pembrolizumab

Overview

Phase: Phase 1
Intervention: NC410
Conditions: Advanced or Metastatic Solid Tumors
Sponsor: NextCure, Inc.
Enrollment: 97
Locations: 17
Primary Endpoint: Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, non-randomized, Phase 1b/2 study to determine the safety and tolerability of NC410 when combined with a standard dose of pembrolizumab. This study will also assess the clinical benefit of combination therapy in participants with advanced unresectable and/or metastatic ICI refractory solid tumors OR ICI naïve MSS/MSI-low solid tumors

Registry

clinicaltrials.gov

Start Date

October 6, 2022

End Date

November 2025

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

NextCure, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Be 18 years of age on day of signing informed consent.
•Participant with histologically or cytologically confirmed diagnosis of the following advanced unresectable and/or metastatic solid tumors:
•Phase 1b: Participants with solid tumors that are known to be associated as MSS/MSI-low in the majority including: CRC (without liver metastasis), Gastric including GE junction, Esophageal, Ovarian, and H\&N cancer (regardless of prior treatment with ICIs). Note: Participants must have had disease progression after at least one line of systemic standard of care therapy prior to enrollment. Participants who discontinue standard treatment due to intolerance or refuse standard treatment will also be eligible to enroll.
•Phase 2 ICI Refractory Solid Tumors (Cohort 1): Participants with solid tumors including CRC, Gastric including GE junction, Esophageal, Endometrial, H\&N, Lung, Cervical and Ovarian cancer.Participants must have progressed on treatment with an anti-PD1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
•Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
•Has demonstrated disease progression after PD-1/L1 as defined by RECIST v1.
•Phase 2 ICI naïve Solid Tumors (Cohorts 2a-2c):Tumors known to be associated with MSS/MSI-low status such as CRC, Gastric including GE junction, and Ovarian cancer where participants have not been previously treated with ICIs. Note: Participants must have had disease progression after at least one line of systemic standard of care therapy prior to enrollment. Participants who discontinue standard treatment due to intolerance or refuse standard treatment will also be eligible to enroll. Note: Confirmation of MSS/MSI status should be assessed prior to study entry (either by historical result or during screening).
•A male participant must agree to use contraception and refrain from sperm donation or expecting to father a child, from Screening through the treatment period and for at least 120 days after the last dose of study treatment.
•A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
•Not a woman of childbearing potential (WOCBP)

Exclusion Criteria

•A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
•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, OX40, CD137), and was discontinued from that treatment due to a Grade 3 or higher irAE.
•Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to treatment. Note: Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤ 2 requiring treatment or hormone replacement may be eligible. If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
•Has received prior radiotherapy within 2 weeks of start of study treatment or has had a history of radiation pneumonitis. Note: Participants must have recovered from all radiation-related toxicities and do not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
•Has received G-CSF or GM-CSF within 7 days prior to start of study treatment.
•Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
•Receipt of COVID-19 vaccine within ≤ 14 days prior to first administration of study treatments. For 2-dose COVID-19 vaccines or COVID-19 booster, participants must wait at least 14-days after administration prior to beginning study treatment.
•Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
•Has had an allogeneic tissue/stem cell/solid organ transplant.
•Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

Arms & Interventions

NC410 and pembrolizumab

All participants will receive NC410 (IV) and pembrolizumab (IV) according to the treatment schedule until a reason for treatment discontinuation is reached.

Intervention: NC410

NC410 and pembrolizumab

All participants will receive NC410 (IV) and pembrolizumab (IV) according to the treatment schedule until a reason for treatment discontinuation is reached.

Intervention: pembrolizumab

Outcomes

Primary Outcomes

Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0

Time Frame: 24 Months

Frequency, duration, and severity of treatment-emergent adverse events (AEs)

Define a recommended Phase 2 dose (RP2D) of NC410 when combined with standard dose Pembrolizumab

Time Frame: 42 days

A mTPI design will be utilized to determine the RP2D of NC410

Secondary Outcomes

Duration of Response per RECIST(until disease progression, up to 24 months)
Objective Response Rate per RECIST(until disease progression, up to 24 months)
Disease Control Rate per RECIST(until disease progression, up to 24 months)
Progression-free Survival (PFS) per RECIST(until disease progression, up to 24 months)