NL-201 Monotherapy and in Combination With Pembrolizumab in Patients With Relapsed or Refractory Cancer

A First-in-Human Phase 1 Study of NL-201 Monotherapy and in Combination With Pembrolizumab in Patients With Relapsed or Refractory Cancer

Parts 1 and 2 The primary purpose of this study is to understand the safety of NL-201 when given intravenously as monotherapy in patients with advanced cancer to evaluate tolerability and to identify a recommended dose and schedule for further testing. In Part 1, there will be backfill cohorts at certain Data Monitoring Committee (DMC)-cleared dose levels and schedules to collect pharmacokinetic (PK), pharmacodynamic (PD) and response data in certain tumor types or to explore additional pre-medication regimens.

Parts 3 and 4 The primary purpose of this study is to understand the safety of NL-201 in combination with pembrolizumab when both drugs are given intravenously in patients with advanced cancer, to evaluate tolerability, and to identify a recommended dose and schedule for further testing.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumor; Advanced Solid Tumor
• Intervention / Treatment: Drug: NL-201; Drug: Pembrolizumab Injection [Keytruda]

Detailed Description

Patients will have tests and exams to see if they are eligible for the clinical trial.

Parts 1 and 2 If eligible, the patient will receive NL-201 treatment by vein. Tumor response to treatment will be assessed every 6 weeks for 12 weeks, and every 12 weeks thereafter until disease progression.

Patients will be able to receive study treatment as long as it is tolerated and there is evidence of clinical benefit. Safety follow-up will occur within 7 days after the last dose of NL-201. Patients will then enter long-term follow-up until starting a subsequent therapy.

In Part 1, there will be backfill cohorts at certain DMC-cleared dose levels and schedules to collect PK, PD and response data in certain tumor types or to explore additional pre-medication regimens.

Parts 3 and 4 If eligible, the patient will receive NL-201 and pembrolizumab treatment by vein. Tumor response to treatment will be assessed every 6 weeks for 12 weeks, and every 12 weeks thereafter until disease progression.

Patients will be able to receive study treatments as long as they are tolerated and there is evidence of clinical benefit. Safety follow-up will occur within 7 days after the last dose of investigational product. Patients will then enter long-term follow-up until starting a subsequent therapy.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2065
      • Melanoma Institute Australia
    • Sydney, New South Wales, Australia
      • St Vincents Hospital
  • Victoria
    • Heidelberg, Victoria, Australia
      • Olivia Newton-John Cancer Wellness & Research Centre
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1Z5
      • UHN - Princess Margaret Cancer Center
• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Center Oncology and Hematology Care Clinic
  • Texas
    • Houston, Texas, United States, 77230
      • UT- MD Anderson
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with measurable disease
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• At least 6 weeks from any prior nitrosurea or mitomycin C therapy; at least 4 weeks from any other prior chemotherapy or checkpoint inhibitor; at least 2 weeks from any kinase inhibitor
• Part 1 Only: Patients with relapsed or refractory advanced solid tumor, other than prostate cancer, who have progressed, not tolerated or are ineligible for all approved lines of therapy
• Part 2 Only: Patients with kidney and skin cancer who have failed at least 1 line of systemic therapy
• Part 3 Only: Patients with solid tumors who have received ≥ 1 prior line of therapy for advanced or metastatic disease
• Part 4 Only: Patients with diagnosed target disease OR previously received pembrolizumab

Exclusion Criteria:

• Prostate Cancer
• Any serious medical condition or laboratory abnormality or psychiatric condition or any other significant or unstable concurrent medical illness (in the opinion of the Investigator) would preclude protocol adherence or would make the safety of the study drug difficult to assess
• Known or suspected SARS-CoV-2 infection, unless patient tests negative for SARS-CoV-2 within the Screening period
• History of solid organ transplant or bone marrow transplant
• Prior chimeric antigen receptor T-cell (CAR-T) or allogeneic cellular therapy
• Prior IL-2-based cancer therapy
• Ongoing systemic immunosuppressive therapy
• Concurrent therapy with any other investigational agent, vaccine, or device.
• Part 3 and 4 Only: History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Part 3 and 4 Only: Known additional cancer that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone curative resection are eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: NL-201 Monotherapy Dose Escalation; NL-201 given as monotherapy by intravenous administration testing ascending doses and two different schedules.	Drug: NL-201; NL-201 is a de novo protein therapeutic.
Experimental: Part 2: NL201 Monotherapy Expansion Cohorts; NL-201 given as monotherapy by intravenous administration in indication specific cohorts at a dose and schedule determined in Part 1.	Drug: NL-201; NL-201 is a de novo protein therapeutic.
Experimental: Part 3: NL-201 in Combination with Pembrolizumab Dose Escalation; NL-201, in combination with a set Pembrolizumab dose, testing ascending doses and two different schedules	Drug: NL-201; NL-201 is a de novo protein therapeutic.; Drug: Pembrolizumab Injection [Keytruda]; A programmed death receptor-1 (PD-1)-blocking antibody; Other Names: MK-3475, Pembrolizumab, Keytruda
Experimental: Part 4: NL-201 in Combination with Pembrolizumab Expansion Cohorts; NL-201 in combination with Pembrolizumab in indication specific cohorts at a dose and schedule determined in Part 3	Drug: NL-201; NL-201 is a de novo protein therapeutic.; Drug: Pembrolizumab Injection [Keytruda]; A programmed death receptor-1 (PD-1)-blocking antibody; Other Names: MK-3475, Pembrolizumab, Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended phase 2 dose (RP2D) for NL-201 (Parts 1 and 2)	Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)	Up to Day 33
Recommended dose schedule for NL-201 (Parts 1 and 2)	Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)	Up to Day 33
Recommended phase 2 dose (RP2D) for NL-201 in combination with Pembrolizumab (Parts 3 and 4)	Evaluation of tolerability of NL-201 in combination with Pembrolizumab as measured by number of subjects with dose limiting toxicities (DLTs)	Up to Day 33
Recommended dose schedule for NL-201 in combination with Pembrolizumab (Parts 3 and 4)	Evaluation of tolerability of NL-201 in combination with Pembrolizumab as measured by number of subjects with dose limiting toxicities (DLTs)	Up to Day 33
Incidence of treatment-emergent adverse events	Rate of adverse events in patients with advanced solid tumors	Up to Day 33
Severity of treatment-emergent adverse events	Rate of adverse event grades in patients with advanced solid tumors	Up to Day 33

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Objective Response according to RECIST version 1.1	Based on Investigator assessment of radiographic imaging	Up to 36 months
Objective Response Rate (ORR) according to RECIST version 1.1	Based on Investigator assessment of radiographic imaging	Up to 36 months
Progression-Free Survival (PFS) according to RECIST version 1.1	Based on Investigator assessment of radiographic imaging	Up to 36 months
Duration of Response (DOR) according to RECIST version 1.1	Based on Investigator assessment of radiographic imaging	Upto 36 months
Pharmacokinetic (PK) profile of NL-201 by half-life (t1/2)	Prespecified timepoints in serum before and after dosing with NL-201.	Up to 24 Months
Pharmacokinetic (PK) profile of NL-201 by area under the plasma concentration time curve (AUC)	Prespecified timepoints in serum before and after dosing with NL-201.	Up to 24 months
Pharmacokinetic (PK) profile of NL-201 by maximum observed plasma concentration (Cmax)	Prespecified timepoints in serum before and after dosing with NL-201.	Up to 24 months
Pharmacokinetic (PK) profile of NL-201 by volume of distribution (Vd)	Prespecified timepoints in serum before and after dosing with NL-201.	Up to 24 Months
Terminal-Phase Elimination Rate Constant (β) of NL-201	Prespecified timepoints in serum before and after dosing with NL-201.	Up to 24 months
Immunogenicity of NL-201	Anti-drug antibodies in serum during and after treatment with NL-201	Up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow cytometry analysis of immune cells in blood	Based on appropriate assay	Up to 36 months
Serum measurements of inflammatory cytokine levels	Based on appropriate assay	Up to 36 months
Analysis of immune characteristics of the tumor microenvironment	Based on appropriate assay	Up to 36 months
Estimate additional measures of anti-tumor activity of NL- 201 per iRECIST criteria	Based on Investigator assessment of imaging	Up to 36 months

Collaborators and Investigators

• Sponsor: Neurogene Inc.
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2021
• Primary Completion (Actual): December 15, 2022
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Immunotherapy; Phase 1; Pembrolizumab; Keytruda; Cytokine; IL-2; MK-3475; IL-15; NL-201; NL201-101
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: NL201-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No