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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04659629
Recruitment Status : Active, not recruiting
First Posted : December 9, 2020
Last Update Posted : December 2, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Neoleukin Therapeutics, Inc.

Study Description
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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 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 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.


Condition or disease Intervention/treatment Phase
Solid Tumor Advanced Solid Tumor Drug: NL-201 Drug: Pembrolizumab Injection [Keytruda] Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A First-in-Human Phase 1 Study of NL-201 Monotherapy and in Combination With Pembrolizumab in Patients With Relapsed or Refractory Cancer
Actual Study Start Date : April 26, 2021
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: MK-3475, Pembrolizumab, Keytruda


Outcome Measures
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Primary Outcome Measures :
  1. Recommended phase 2 dose (RP2D) for NL-201 (Parts 1 and 2) [ Time Frame: Up to Day 33 ]
    Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)

  2. Recommended dose schedule for NL-201 (Parts 1 and 2) [ Time Frame: Up to Day 33 ]
    Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)

  3. Recommended phase 2 dose (RP2D) for NL-201 in combination with Pembrolizumab (Parts 3 and 4) [ Time Frame: Up to Day 33 ]
    Evaluation of tolerability of NL-201 in combination with Pembrolizumab as measured by number of subjects with dose limiting toxicities (DLTs)

  4. Recommended dose schedule for NL-201 in combination with Pembrolizumab (Parts 3 and 4) [ Time Frame: Up to Day 33 ]
    Evaluation of tolerability of NL-201 in combination with Pembrolizumab as measured by number of subjects with dose limiting toxicities (DLTs)

  5. Incidence of treatment-emergent adverse events [ Time Frame: Up to Day 33 ]
    Rate of adverse events in patients with advanced solid tumors

  6. Severity of treatment-emergent adverse events [ Time Frame: Up to Day 33 ]
    Rate of adverse event grades in patients with advanced solid tumors


Secondary Outcome Measures :
  1. Best Objective Response according to RECIST version 1.1 [ Time Frame: Up to 36 months ]
    Based on Investigator assessment of radiographic imaging

  2. Objective Response Rate (ORR) according to RECIST version 1.1 [ Time Frame: Up to 36 months ]
    Based on Investigator assessment of radiographic imaging

  3. Progression-Free Survival (PFS) according to RECIST version 1.1 [ Time Frame: Up to 36 months ]
    Based on Investigator assessment of radiographic imaging

  4. Duration of Response (DOR) according to RECIST version 1.1 [ Time Frame: Upto 36 months ]
    Based on Investigator assessment of radiographic imaging

  5. Pharmacokinetic (PK) profile of NL-201 by half-life (t1/2) [ Time Frame: Up to 24 Months ]
    Prespecified timepoints in serum before and after dosing with NL-201.

  6. Pharmacokinetic (PK) profile of NL-201 by area under the plasma concentration time curve (AUC) [ Time Frame: Up to 24 months ]
    Prespecified timepoints in serum before and after dosing with NL-201.

  7. Pharmacokinetic (PK) profile of NL-201 by maximum observed plasma concentration (Cmax) [ Time Frame: Up to 24 months ]
    Prespecified timepoints in serum before and after dosing with NL-201.

  8. Pharmacokinetic (PK) profile of NL-201 by volume of distribution (Vd) [ Time Frame: Up to 24 Months ]
    Prespecified timepoints in serum before and after dosing with NL-201.

  9. Terminal-Phase Elimination Rate Constant (β) of NL-201 [ Time Frame: Up to 24 months ]
    Prespecified timepoints in serum before and after dosing with NL-201.

  10. Immunogenicity of NL-201 [ Time Frame: Up to 24 months ]
    Anti-drug antibodies in serum during and after treatment with NL-201


Other Outcome Measures:
  1. Flow cytometry analysis of immune cells in blood [ Time Frame: Up to 36 months ]
    Based on appropriate assay

  2. Serum measurements of inflammatory cytokine levels [ Time Frame: Up to 36 months ]
    Based on appropriate assay

  3. Analysis of immune characteristics of the tumor microenvironment [ Time Frame: Up to 36 months ]
    Based on appropriate assay

  4. Estimate additional measures of anti-tumor activity of NL- 201 per iRECIST criteria [ Time Frame: Up to 36 months ]
    Based on Investigator assessment of imaging


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04659629


Locations
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United States, Arizona
Mayo Clinic Scottsdale/ Phoenix
Phoenix, Arizona, United States, 85054
United States, California
City of Hope
Duarte, California, United States, 91010
UCLA
Los Angeles, California, United States, 90095
UC San Diego Moores Cancer Center
San Diego, California, United States, 92037
United States, Florida
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, New York
Westchester Medical Center
Valhalla, New York, United States, 10595
United States, Oregon
Providence Cancer Center Oncology and Hematology Care Clinic
Portland, Oregon, United States, 97213
United States, Texas
UT- MD Anderson
Houston, Texas, United States, 77230
United States, Utah
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, United States, 80045
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Australia, New South Wales
Melanoma Institute Australia
Sydney, New South Wales, Australia, 2065
St Vincents Hospital
Sydney, New South Wales, Australia
Australia, Victoria
Olivia Newton-John Cancer Wellness & Research Centre
Heidelberg, Victoria, Australia
Cabrini Hospital Malvern
Malvern, Victoria, Australia
Canada, Ontario
UHN - Princess Margaret Cancer Center
Toronto, Ontario, Canada, M5G1Z5
Sponsors and Collaborators
Neoleukin Therapeutics, Inc.
Merck Sharp & Dohme LLC
More Information
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Responsible Party: Neoleukin Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04659629    
Other Study ID Numbers: NL201-101
First Posted: December 9, 2020    Key Record Dates
Last Update Posted: December 2, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Neoleukin Therapeutics, Inc.:
Cancer
NL-201
NL201-101
Phase 1
Immunotherapy
Cytokine
 Pembrolizumab
Keytruda
IL-2
IL-15
MK-3475
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
 Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action