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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04659629




Registration number
NCT04659629
Ethics application status
Date submitted
9/11/2020
Date registered
9/12/2020
Date last updated
12/03/2024

Titles & IDs
Public title
NL-201 Monotherapy and in Combination With Pembrolizumab in Patients With Relapsed or Refractory Cancer
Scientific title
A First-in-Human Phase 1 Study of NL-201 Monotherapy and in Combination With Pembrolizumab in Patients With Relapsed or Refractory Cancer
Secondary ID [1] 0 0
NL201-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Advanced Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NL-201
Treatment: Drugs - Pembrolizumab Injection [Keytruda]

Experimental: Part 1: NL-201 Monotherapy Dose Escalation - NL-201 given as monotherapy by intravenous administration testing ascending doses and two different schedules.

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.

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

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


Treatment: Drugs: NL-201
NL-201 is a de novo protein therapeutic.

Treatment: Drugs: Pembrolizumab Injection [Keytruda]
A programmed death receptor-1 (PD-1)-blocking antibody
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended phase 2 dose (RP2D) for NL-201 (Parts 1 and 2)
Timepoint [1] 0 0
Up to Day 33
Primary outcome [2] 0 0
Recommended dose schedule for NL-201 (Parts 1 and 2)
Timepoint [2] 0 0
Up to Day 33
Primary outcome [3] 0 0
Recommended phase 2 dose (RP2D) for NL-201 in combination with Pembrolizumab (Parts 3 and 4)
Timepoint [3] 0 0
Up to Day 33
Primary outcome [4] 0 0
Recommended dose schedule for NL-201 in combination with Pembrolizumab (Parts 3 and 4)
Timepoint [4] 0 0
Up to Day 33
Primary outcome [5] 0 0
Incidence of treatment-emergent adverse events
Timepoint [5] 0 0
Up to Day 33
Primary outcome [6] 0 0
Severity of treatment-emergent adverse events
Timepoint [6] 0 0
Up to Day 33
Secondary outcome [1] 0 0
Best Objective Response according to RECIST version 1.1
Timepoint [1] 0 0
Up to 36 months
Secondary outcome [2] 0 0
Objective Response Rate (ORR) according to RECIST version 1.1
Timepoint [2] 0 0
Up to 36 months
Secondary outcome [3] 0 0
Progression-Free Survival (PFS) according to RECIST version 1.1
Timepoint [3] 0 0
Up to 36 months
Secondary outcome [4] 0 0
Duration of Response (DOR) according to RECIST version 1.1
Timepoint [4] 0 0
Upto 36 months
Secondary outcome [5] 0 0
Pharmacokinetic (PK) profile of NL-201 by half-life (t1/2)
Timepoint [5] 0 0
Up to 24 Months
Secondary outcome [6] 0 0
Pharmacokinetic (PK) profile of NL-201 by area under the plasma concentration time curve (AUC)
Timepoint [6] 0 0
Up to 24 months
Secondary outcome [7] 0 0
Pharmacokinetic (PK) profile of NL-201 by maximum observed plasma concentration (Cmax)
Timepoint [7] 0 0
Up to 24 months
Secondary outcome [8] 0 0
Pharmacokinetic (PK) profile of NL-201 by volume of distribution (Vd)
Timepoint [8] 0 0
Up to 24 Months
Secondary outcome [9] 0 0
Terminal-Phase Elimination Rate Constant (ß) of NL-201
Timepoint [9] 0 0
Up to 24 months
Secondary outcome [10] 0 0
Immunogenicity of NL-201
Timepoint [10] 0 0
Up to 24 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2024
Actual
Sample size
Target
Accrual to date
Final
59
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Melanoma Institute Australia - Sydney
Recruitment hospital [2] 0 0
St Vincents Hospital - Sydney
Recruitment hospital [3] 0 0
Olivia Newton-John Cancer Wellness & Research Centre - Heidelberg
Recruitment postcode(s) [1] 0 0
2065 - Sydney
Recruitment postcode(s) [2] 0 0
- Sydney
Recruitment postcode(s) [3] 0 0
- Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
Oregon
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Neurogene Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04659629
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04659629