Solid TumorPhase 1NCT04659629
NL-201 Monotherapy and in Combination With Pembrolizumab in Patients With Relapsed or Refractory Cancer
A Phase 1 study testing NL-201 and Pembrolizumab Injection [Keytruda] in people with Solid Tumor and Advanced Solid Tumor, run by Neurogene Inc. at 8 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Advanced Solid Tumor
- What is being tested?
- NL-201 and Pembrolizumab Injection [Keytruda]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 8 sitesin 3 countries
- Study dates
- 26 Apr 2021to 15 Aug 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
United States4 sites
UT- MD Anderson
Houston, Texas, 77230
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Providence Cancer Center Oncology and Hematology Care Clinic
Portland, Oregon, 97213
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Australia3 sites
Olivia Newton-John Cancer Wellness & Research Centre
Heidelberg, Victoria
Melanoma Institute Australia
Sydney, New South Wales, 2065
St Vincents Hospital
Sydney, New South Wales
About this study
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
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.
Read the 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.
- Conditions
- Solid Tumor, Advanced Solid Tumor
- Being tested
- NL-201, Pembrolizumab Injection [Keytruda]
- Keywords
- Cancer, NL-201, NL201-101, Phase 1, Immunotherapy, Cytokine, Pembrolizumab, Keytruda, IL-2, IL-15, MK-3475
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NL-201Drug
NL-201 is a de novo protein therapeutic.
Pembrolizumab Injection [Keytruda]Drug
Also called MK-3475, Pembrolizumab, Keytruda
A programmed death receptor-1 (PD-1)-blocking antibody
| Study group | Role | What they receive |
|---|---|---|
| Part 1: NL-201 Monotherapy Dose Escalation | Experimental | NL-201 given as monotherapy by intravenous administration testing ascending doses and two different schedules. Receives: Drug: NL-201 |
| Part 2: NL201 Monotherapy Expansion Cohorts | Experimental | NL-201 given as monotherapy by intravenous administration in indication specific cohorts at a dose and schedule determined in Part 1. Receives: Drug: NL-201 |
| Part 3: NL-201 in Combination with Pembrolizumab Dose Escalation | Experimental | NL-201, in combination with a set Pembrolizumab dose, testing ascending doses and two different schedules Receives: Drug: NL-201; Drug: Pembrolizumab Injection [Keytruda] |
| Part 4: NL-201 in Combination with Pembrolizumab Expansion Cohorts | Experimental | NL-201 in combination with Pembrolizumab in indication specific cohorts at a dose and schedule determined in Part 3 Receives: Drug: NL-201; Drug: Pembrolizumab Injection [Keytruda] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase 2 dose (RP2D) for NL-201 (Parts 1 and 2)
Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)
Measured: Up to Day 33
Recommended dose schedule for NL-201 (Parts 1 and 2)
Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)
Measured: Up to Day 33
Recommended phase 2 dose (RP2D) for NL-201 in combination with Pembrolizumab (Parts 3 and 4)
Evaluation of tolerability of NL-201 in combination with Pembrolizumab as measured by number of subjects with dose limiting toxicities (DLTs)
Measured: Up to Day 33
Recommended dose schedule for NL-201 in combination with Pembrolizumab (Parts 3 and 4)
Evaluation of tolerability of NL-201 in combination with Pembrolizumab as measured by number of subjects with dose limiting toxicities (DLTs)
Measured: Up to Day 33
Incidence of treatment-emergent adverse events
Rate of adverse events in patients with advanced solid tumors
Measured: Up to Day 33
Severity of treatment-emergent adverse events
Rate of adverse event grades in patients with advanced solid tumors
Measured: Up to Day 33
Secondary outcomes (10)
Best Objective Response according to RECIST version 1.1
Based on Investigator assessment of radiographic imaging
Measured: Up to 36 months
Objective Response Rate (ORR) according to RECIST version 1.1
Based on Investigator assessment of radiographic imaging
Measured: Up to 36 months
Progression-Free Survival (PFS) according to RECIST version 1.1
Based on Investigator assessment of radiographic imaging
Measured: Up to 36 months
Duration of Response (DOR) according to RECIST version 1.1
Based on Investigator assessment of radiographic imaging
Measured: Upto 36 months
Pharmacokinetic (PK) profile of NL-201 by half-life (t1/2)
Prespecified timepoints in serum before and after dosing with NL-201.
Measured: Up to 24 Months
Pharmacokinetic (PK) profile of NL-201 by area under the plasma concentration time curve (AUC)
Prespecified timepoints in serum before and after dosing with NL-201.
Measured: Up to 24 months
Pharmacokinetic (PK) profile of NL-201 by maximum observed plasma concentration (Cmax)
Prespecified timepoints in serum before and after dosing with NL-201.
Measured: Up to 24 months
Pharmacokinetic (PK) profile of NL-201 by volume of distribution (Vd)
Prespecified timepoints in serum before and after dosing with NL-201.
Measured: Up to 24 Months
Terminal-Phase Elimination Rate Constant (β) of NL-201
Prespecified timepoints in serum before and after dosing with NL-201.
Measured: Up to 24 months
Immunogenicity of NL-201
Anti-drug antibodies in serum during and after treatment with NL-201
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2020
- Study start26 Apr 2021
- Primary completion15 Dec 2022
- Study completion15 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurogene Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Albiruni A Razak, Principal investigator, UHN - Princess Margaret Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04659629
- Sponsor's protocol ID
- NL201-101
- Status last verified
- Sep 2024
- First submitted
- 9 Nov 2020
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04659629
- Acronym / sponsor ID
- NL201-101
- Conditions
- Solid Tumor, Advanced Solid Tumor
- Keywords
- Cancer, NL-201, NL201-101, Phase 1, Immunotherapy, Cytokine, Pembrolizumab, Keytruda
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Neurogene Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 26 Apr 2021 (actual)
- Primary completion
- 15 Dec 2022 (actual)
- Study completion
- 15 Aug 2024 (actual)
- First posted
- 9 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1: NL-201 Monotherapy Dose Escalation | Experimental | Drug: NL-201NL-201 given as monotherapy by intravenous administration testing ascending doses and two different schedules. |
| Part 2: NL201 Monotherapy Expansion Cohorts | Experimental | Drug: NL-201NL-201 given as monotherapy by intravenous administration in indication specific cohorts at a dose and schedule determined in Part 1. |
| Part 3: NL-201 in Combination with Pembrolizumab Dose Escalation | Experimental | Drug: NL-201, Drug: Pembrolizumab Injection [Keytruda]NL-201, in combination with a set Pembrolizumab dose, testing ascending doses and two different schedules |
| Part 4: NL-201 in Combination with Pembrolizumab Expansion Cohorts | Experimental | Drug: NL-201, Drug: Pembrolizumab Injection [Keytruda]NL-201 in combination with Pembrolizumab in indication specific cohorts at a dose and schedule determined in Part 3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NL-201NL-201 is a de novo protein therapeutic. | Drug | Part 1: NL-201 Monotherapy Dose Escalation, Part 2: NL201 Monotherapy Expansion Cohorts, Part 3: NL-201 in Combination with Pembrolizumab Dose Escalation, Part 4: NL-201 in Combination with Pembrolizumab Expansion Cohorts |
| Pembrolizumab Injection [Keytruda]Also: MK-3475, Pembrolizumab, KeytrudaA programmed death receptor-1 (PD-1)-blocking antibody | Drug | Part 3: NL-201 in Combination with Pembrolizumab Dose Escalation, Part 4: NL-201 in Combination with Pembrolizumab Expansion Cohorts |
Primary outcome
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
10 secondary outcomes
Best Objective Response according to RECIST version 1.1
Time frame: Up to 36 months
Objective Response Rate (ORR) according to RECIST version 1.1
Time frame: Up to 36 months
Progression-Free Survival (PFS) according to RECIST version 1.1
Time frame: Up to 36 months
Duration of Response (DOR) according to RECIST version 1.1
Time frame: Upto 36 months
Pharmacokinetic (PK) profile of NL-201 by half-life (t1/2)
Time frame: Up to 24 Months
Pharmacokinetic (PK) profile of NL-201 by area under the plasma concentration time curve (AUC)
Time frame: Up to 24 months
Pharmacokinetic (PK) profile of NL-201 by maximum observed plasma concentration (Cmax)
Time frame: Up to 24 months
Pharmacokinetic (PK) profile of NL-201 by volume of distribution (Vd)
Time frame: Up to 24 Months
Terminal-Phase Elimination Rate Constant (β) of NL-201
Time frame: Up to 24 months
Immunogenicity of NL-201
Time frame: Up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Individual participant dataSharing planned: No
Related trials for Solid Tumor
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albiruni A Razak principal investigator
UHN - Princess Margaret Cancer Center
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NL-201 and Pembrolizumab Injection [Keytruda] in people with Solid Tumor and Advanced Solid Tumor, run by Neurogene Inc. at 8 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase 2 dose (RP2D) for NL-201 (Parts 1 and 2) (time frame: Up to Day 33). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024.