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NL-201 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04659629
Recruitment Status : Recruiting
First Posted : December 9, 2020
Last Update Posted : February 28, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Neoleukin Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE November 9, 2020
First Posted Date  ICMJE December 9, 2020
Last Update Posted Date February 28, 2022
Actual Study Start Date  ICMJE April 26, 2021
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 9, 2022)
  • 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)
  • 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)
  • 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)
  • Recommended dose schedule for NL-201 in 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)
  • Incidence of treatment-emergent adverse events [ Time Frame: Up to Day 33 ]
    Rate of adverse events in patients with advanced solid tumors
  • Severity of treatment-emergent adverse events [ Time Frame: Up to Day 33 ]
    Rate of adverse event grades in patients with advanced solid tumors
Original Primary Outcome Measures  ICMJE
 (submitted: December 2, 2020)
  • Recommended phase 2 dose (RP2D) for NL-201 [ Time Frame: Up to Day 33 ]
    Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)
  • Recommended dose schedule for NL-201 [ Time Frame: Up to Day 33 ]
    Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)
  • Incidence of treatment-emergent adverse events [ Time Frame: Up to Day 33 ]
    Rate of adverse events in patients with advanced solid tumors
  • Severity of treatment-emergent adverse events [ Time Frame: Up to Day 33 ]
    Rate of adverse event grades in patients with advanced solid tumors
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2020)
  • Best Objective Response according to RECIST version 1.1 [ Time Frame: Up to 36 months ]
    Based on Investigator assessment of radiographic imaging
  • Objective Response Rate (ORR) according to RECIST version 1.1 [ Time Frame: Up to 36 months ]
    Based on Investigator assessment of radiographic imaging
  • Progression-Free Survival (PFS) according to RECIST version 1.1 [ Time Frame: Up to 36 months ]
    Based on Investigator assessment of radiographic imaging
  • Duration of Response (DOR) according to RECIST version 1.1 [ Time Frame: Upto 36 months ]
    Based on Investigator assessment of radiographic imaging
  • 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.
  • 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.
  • 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.
  • 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.
  • Immunogenicity of NL-201 [ Time Frame: Up to 24 months ]
    Anti-drug antibodies in serum during and after treatment with NL-201
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: December 2, 2020)
  • Flow cytometry analysis of immune cells in blood [ Time Frame: Up to 36 months ]
    Based on appropriate assay
  • Serum measurements of inflammatory cytokine levels [ Time Frame: Up to 36 months ]
    Based on appropriate assay
  • Analysis of immune characteristics of the tumor microenvironment [ Time Frame: Up to 36 months ]
    Based on appropriate assay
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE NL-201 in Patients With Relapsed or Refractory Cancer
Official Title  ICMJE A First-in-Human Phase 1 Study of NL-201 in Patients With Relapsed or Refractory Cancer
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.

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.

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor
  • Advanced Solid Tumor
Intervention  ICMJE
  • 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: Pembrolizumab
Study Arms  ICMJE
  • Experimental: Part 1: NL-201 Monotherapy Dose Escalation
    NL-201 given as monotherapy by intravenous administration testing ascending doses and two different schedules.
    Intervention: Drug: NL-201
  • 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.
    Intervention: Drug: NL-201
  • 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
    Interventions:
    • Drug: NL-201
    • Drug: Pembrolizumab Injection [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
    Interventions:
    • Drug: NL-201
    • Drug: Pembrolizumab Injection [Keytruda]
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 9, 2022)
252
Original Estimated Enrollment  ICMJE
 (submitted: December 2, 2020)
120
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Susan Luebbe 800-718-4951 sluebbe@neoleukin.com
Contact: Sterling Chung 800-718-4951 schung@neoleukin.com
Listed Location Countries  ICMJE Australia,   Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04659629
Other Study ID Numbers  ICMJE NL201-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Neoleukin Therapeutics, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Neoleukin Therapeutics, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Merck Sharp & Dohme LLC
Investigators  ICMJE
Study Director: Cynthia Wetmore, MD, PhD Neoleukin
PRS Account Neoleukin Therapeutics, Inc.
Verification Date February 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP