Clinical trial NCT04659629: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Advanced Solid Tumor
Keywords: Cancer
NL-201
NL201-101
Phase 1
Immunotherapy
Cytokine
Pembrolizumab
Keytruda
IL-2
IL-15
MK-3475
Lead sponsor: Neurogene Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2020-12-09
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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 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.

Primary outcomes:
measure: Recommended phase 2 dose (RP2D) for NL-201 (Parts 1 and 2)
timeFrame: Up to Day 33
measure: Recommended dose schedule for NL-201 (Parts 1 and 2)
timeFrame: Up to Day 33
measure: Recommended phase 2 dose (RP2D) for NL-201 in combination with Pembrolizumab (Parts 3 and 4)
timeFrame: Up to Day 33
measure: Recommended dose schedule for NL-201 in combination with Pembrolizumab (Parts 3 and 4)
timeFrame: Up to Day 33
measure: Incidence of treatment-emergent adverse events
timeFrame: Up to Day 33
measure: Severity of treatment-emergent adverse events
timeFrame: Up to Day 33
Secondary outcomes:
measure: Best Objective Response according to RECIST version 1.1
timeFrame: Up to 36 months
measure: Objective Response Rate (ORR) according to RECIST version 1.1
timeFrame: Up to 36 months
measure: Progression-Free Survival (PFS) according to RECIST version 1.1
timeFrame: Up to 36 months
measure: Duration of Response (DOR) according to RECIST version 1.1
timeFrame: Upto 36 months
measure: Pharmacokinetic (PK) profile of NL-201 by half-life (t1/2)
timeFrame: Up to 24 Months
measure: Pharmacokinetic (PK) profile of NL-201 by area under the plasma concentration time curve (AUC)
timeFrame: Up to 24 months
measure: Pharmacokinetic (PK) profile of NL-201 by maximum observed plasma concentration (Cmax)
timeFrame: Up to 24 months
measure: Pharmacokinetic (PK) profile of NL-201 by volume of distribution (Vd)
timeFrame: Up to 24 Months
measure: Terminal-Phase Elimination Rate Constant (β) of NL-201
timeFrame: Up to 24 months
measure: Immunogenicity of NL-201
timeFrame: Up to 24 months
Other outcomes:
measure: Flow cytometry analysis of immune cells in blood
timeFrame: Up to 36 months
measure: Serum measurements of inflammatory cytokine levels
timeFrame: Up to 36 months
measure: Analysis of immune characteristics of the tumor microenvironment
timeFrame: Up to 36 months
measure: Estimate additional measures of anti-tumor activity of NL- 201 per iRECIST criteria
timeFrame: Up to 36 months
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Providence Cancer Center Oncology and Hematology Care Clinic
state: Oregon
city: Houston
country: United States
facility: UT- MD Anderson
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Sydney
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
city: Sydney
country: Australia
facility: St Vincents Hospital
state: New South Wales
city: Heidelberg
country: Australia
facility: Olivia Newton-John Cancer Wellness & Research Centre
state: Victoria
city: Toronto
country: Canada
facility: UHN - Princess Margaret Cancer Center
state: Ontario
Study officials:
affiliation: UHN - Princess Margaret Cancer Center
name: Albiruni A Razak
role: PRINCIPAL_INVESTIGATOR
References: