Solid Tumor, Advanced Solid Tumor
Conditions
Keywords
Cancer, NL-201, NL201-101, Phase 1, Immunotherapy, Cytokine, Pembrolizumab, Keytruda, IL-2, IL-15, MK-3475
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.
Interventions
DRUGNL-201
NL-201 is a de novo protein therapeutic.
A programmed death receptor-1 (PD-1)-blocking antibody
Sponsors
Merck Sharp & Dohme LLC
Neurogene Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended phase 2 dose (RP2D) for NL-201 in combination with Pembrolizumab (Parts 3 and 4) | 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) |
| Severity of treatment-emergent adverse events | Up to Day 33 | Rate of adverse event grades in patients with advanced solid tumors |
| Incidence of treatment-emergent adverse events | Up to Day 33 | Rate of adverse events in patients with advanced solid tumors |
| Recommended dose schedule for NL-201 in combination with Pembrolizumab (Parts 3 and 4) | 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 phase 2 dose (RP2D) for NL-201 (Parts 1 and 2) | 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) | Up to Day 33 | Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) profile of NL-201 by area under the plasma concentration time curve (AUC) | 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) | Up to 24 Months | Prespecified timepoints in serum before and after dosing with NL-201. |
| Terminal-Phase Elimination Rate Constant (β) of NL-201 | Up to 24 months | Prespecified timepoints in serum before and after dosing with NL-201. |
| Immunogenicity of NL-201 | Up to 24 months | Anti-drug antibodies in serum during and after treatment with NL-201 |
| Pharmacokinetic (PK) profile of NL-201 by maximum observed plasma concentration (Cmax) | Up to 24 months | Prespecified timepoints in serum before and after dosing with NL-201. |
| Best Objective Response according to RECIST version 1.1 | Up to 36 months | Based on Investigator assessment of radiographic imaging |
| Objective Response Rate (ORR) according to RECIST version 1.1 | Up to 36 months | Based on Investigator assessment of radiographic imaging |
| Progression-Free Survival (PFS) according to RECIST version 1.1 | Up to 36 months | Based on Investigator assessment of radiographic imaging |
| Duration of Response (DOR) according to RECIST version 1.1 | Upto 36 months | Based on Investigator assessment of radiographic imaging |
| Pharmacokinetic (PK) profile of NL-201 by half-life (t1/2) | Up to 24 Months | Prespecified timepoints in serum before and after dosing with NL-201. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Flow cytometry analysis of immune cells in blood | Up to 36 months | Based on appropriate assay |
| Estimate additional measures of anti-tumor activity of NL- 201 per iRECIST criteria | Up to 36 months | Based on Investigator assessment of imaging |
| Analysis of immune characteristics of the tumor microenvironment | Up to 36 months | Based on appropriate assay |
| Serum measurements of inflammatory cytokine levels | Up to 36 months | Based on appropriate assay |
Countries
Australia, Canada, United States
Outcome results
None listed