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

• ClinicalTrials.gov Identifier: NCT04659629
• Recruitment Status: Active, not recruiting
• First Posted: December 9, 2020
• Last Update Posted: December 2, 2022
• Sponsor: Neoleukin Therapeutics, Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Neoleukin Therapeutics, Inc.

Tracking Information

• First Submitted Date: November 9, 2020
• First Posted Date: December 9, 2020
• Last Update Posted Date: December 2, 2022
• Actual Study Start Date: April 26, 2021
• Estimated Primary Completion Date: May 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 4, 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 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 (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

Current Secondary Outcome Measures (submitted: October 4, 2022)

• 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.
• 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.
• 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 (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

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

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.

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
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Solid Tumor
• Advanced Solid Tumor

Intervention

• 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

Study Arms

• 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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 4, 2022): 310
• Original Estimated Enrollment (submitted: December 2, 2020): 120
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: May 2023 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, United States

Administrative Information

• NCT Number: NCT04659629
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Neoleukin Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Neoleukin Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Not Provided
• PRS Account: Neoleukin Therapeutics, Inc.
• Verification Date: November 2022