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

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04659629
• Other study ID #: NL201-101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: April 26, 2021
• Est. completion date: August 2024

Study information

• Verified date: March 2024
• Source: Neurogene Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 59
• Est. completion date: August 2024
• Est. primary completion date: December 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms
• Solid Tumor

Intervention

Drug:
• NL-201
NL-201 is a de novo protein therapeutic.
• Pembrolizumab Injection [Keytruda]
A programmed death receptor-1 (PD-1)-blocking antibody

Locations

Country	Name	City	State
Australia	Olivia Newton-John Cancer Wellness & Research Centre	Heidelberg	Victoria
Australia	Melanoma Institute Australia	Sydney	New South Wales
Australia	St Vincents Hospital	Sydney	New South Wales
Canada	UHN - Princess Margaret Cancer Center	Toronto	Ontario
United States	UT- MD Anderson	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Providence Cancer Center Oncology and Hematology Care Clinic	Portland	Oregon
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Neurogene Inc.	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Flow cytometry analysis of immune cells in blood	Based on appropriate assay	Up to 36 months
Other	Serum measurements of inflammatory cytokine levels	Based on appropriate assay	Up to 36 months
Other	Analysis of immune characteristics of the tumor microenvironment	Based on appropriate assay	Up to 36 months
Other	Estimate additional measures of anti-tumor activity of NL- 201 per iRECIST criteria	Based on Investigator assessment of imaging	Up to 36 months
Primary	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)	Up to Day 33
Primary	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)	Up to Day 33
Primary	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)	Up to Day 33
Primary	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)	Up to Day 33
Primary	Incidence of treatment-emergent adverse events	Rate of adverse events in patients with advanced solid tumors	Up to Day 33
Primary	Severity of treatment-emergent adverse events	Rate of adverse event grades in patients with advanced solid tumors	Up to Day 33
Secondary	Best Objective Response according to RECIST version 1.1	Based on Investigator assessment of radiographic imaging	Up to 36 months
Secondary	Objective Response Rate (ORR) according to RECIST version 1.1	Based on Investigator assessment of radiographic imaging	Up to 36 months
Secondary	Progression-Free Survival (PFS) according to RECIST version 1.1	Based on Investigator assessment of radiographic imaging	Up to 36 months
Secondary	Duration of Response (DOR) according to RECIST version 1.1	Based on Investigator assessment of radiographic imaging	Upto 36 months
Secondary	Pharmacokinetic (PK) profile of NL-201 by half-life (t1/2)	Prespecified timepoints in serum before and after dosing with NL-201.	Up to 24 Months
Secondary	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.	Up to 24 months
Secondary	Pharmacokinetic (PK) profile of NL-201 by maximum observed plasma concentration (Cmax)	Prespecified timepoints in serum before and after dosing with NL-201.	Up to 24 months
Secondary	Pharmacokinetic (PK) profile of NL-201 by volume of distribution (Vd)	Prespecified timepoints in serum before and after dosing with NL-201.	Up to 24 Months
Secondary	Terminal-Phase Elimination Rate Constant (ß) of NL-201	Prespecified timepoints in serum before and after dosing with NL-201.	Up to 24 months
Secondary	Immunogenicity of NL-201	Anti-drug antibodies in serum during and after treatment with NL-201	Up to 24 months