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

NCT04659629 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: NL201-101
• Study Type: interventional
• Target: 59
• Locations: 3 countries
• Sites: 8

Brief Summary

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.

Conditions

Solid Tumor; Advanced Solid Tumor

Keywords

Cancer; NL-201; NL201-101; Phase 1; Immunotherapy; Cytokine; Pembrolizumab; Keytruda; IL-2; IL-15; MK-3475

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (10)

• Best Objective Response according to RECIST version 1.1

  Up to 36 months

• Objective Response Rate (ORR) according to RECIST version 1.1

  Up to 36 months

• Progression-Free Survival (PFS) according to RECIST version 1.1

  Up to 36 months

• Duration of Response (DOR) according to RECIST version 1.1

  Upto 36 months

• Pharmacokinetic (PK) profile of NL-201 by half-life (t1/2)

  Up to 24 Months

Other Outcomes (4)

• Flow cytometry analysis of immune cells in blood

  Up to 36 months

• Serum measurements of inflammatory cytokine levels

  Up to 36 months

• Analysis of immune characteristics of the tumor microenvironment

  Up to 36 months

Study Arms (4)

Part 1: NL-201 Monotherapy Dose Escalation

EXPERIMENTAL

NL-201 given as monotherapy by intravenous administration testing ascending doses and two different schedules.

Drug: NL-201

Part 2: NL201 Monotherapy Expansion Cohorts

EXPERIMENTAL

NL-201 given as monotherapy by intravenous administration in indication specific cohorts at a dose and schedule determined in Part 1.

Drug: NL-201

Part 3: NL-201 in Combination with Pembrolizumab Dose Escalation

EXPERIMENTAL

NL-201, in combination with a set Pembrolizumab dose, testing ascending doses and two different schedules

Drug: NL-201; Drug: Pembrolizumab Injection [Keytruda]

Part 4: NL-201 in Combination with Pembrolizumab Expansion Cohorts

EXPERIMENTAL

NL-201 in combination with Pembrolizumab in indication specific cohorts at a dose and schedule determined in Part 3

Drug: NL-201; Drug: Pembrolizumab Injection [Keytruda]

Interventions

NL-201 DRUG

NL-201 is a de novo protein therapeutic.

Part 1: NL-201 Monotherapy Dose Escalation; Part 2: NL201 Monotherapy Expansion Cohorts; Part 3: NL-201 in Combination with Pembrolizumab Dose Escalation; Part 4: NL-201 in Combination with Pembrolizumab Expansion Cohorts

Pembrolizumab Injection [Keytruda] DRUG

A programmed death receptor-1 (PD-1)-blocking antibody

Also known as: MK-3475, Pembrolizumab, Keytruda

Part 3: NL-201 in Combination with Pembrolizumab Dose Escalation; Part 4: NL-201 in Combination with Pembrolizumab Expansion Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neurogene Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (8)

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Providence Cancer Center Oncology and Hematology Care Clinic

Portland, Oregon, 97213, United States

Location

UT- MD Anderson

Houston, Texas, 77230, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Melanoma Institute Australia

Sydney, New South Wales, 2065, Australia

Location

St Vincents Hospital

Sydney, New South Wales, Australia

Location

Olivia Newton-John Cancer Wellness & Research Centre

Heidelberg, Victoria, Australia

Location

UHN - Princess Margaret Cancer Center

Toronto, Ontario, M5G1Z5, Canada

Location

MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab

Study Officials

• Albiruni A Razak

  UHN - Princess Margaret Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2020
• First Posted: December 9, 2020
• Study Start: April 26, 2021
• Primary Completion: December 15, 2022
• Study Completion: August 15, 2024
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (4); AU (3)