Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
NPX887 is a human, antagonistic immunoglobulin G1 (IgG1) monoclonal antibody targeting B7-H7 (HHLA2) that may potentiate an anti-tumor immune response. The goal of this first-in-human study is to learn whether NPX887 is safe and tolerable and shows a preliminary efficacy in participants with B7-H7 (HHLA2) expressing tumors at selected dose(s). The main questions it aims to answer are:
Participants who are treated will receive an intravenous (IV) infusion of NPX887 if their disease has not progressed, and be closely monitored by the treating physicians.
This study is comprised of Phase 1a (Dose Escalation) and Phase 1b including Part 1b (Dose Expansion) and Part 1c (Randomized Dose Comparison). Phase 1a will test different doses of NPX887 to determine the optimal dose(s) to continue with in Phase 1b. In the Phase 1b, more participants will be tested to evaluate preliminary activities in multiple disease-specific cohorts and compare the efficacy of the higher and lower doses chosen in Phase 1a.
Throughout the study, safety and preliminary efficacy data will be collected to characterize the clinical activity of NPX887. Samples of blood will be taken to help in an understanding of how NPX887 behaves in the body by assessing the amount of drug in the blood over time, and changes in blood components. Tumor tissue samples will be collected at screening and on-treatment stages for biomarker analysis and pharmacodynamics (PD) evaluation.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NPX887 Treatment | Experimental | Participants will receive NPX887 by IV infusion every 3 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NPX887 | Drug | NPX887 will be administered by IV infusion every 3 weeks until documented disease progression or participant withdrawal for up to 2 years |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of dose limiting toxicity (DLT) | Number of participants with DLT in Ph1a | From first dose through 21 days |
| Incidence of treatment-emergent adverse events (AEs) | Number and type of AEs categorized by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 in Ph1a | From first dose up to 24 months |
| Incidence of discontinuations, dosing interruptions, and dose reductions | Number of participants with changes to their dosing schedule as a result of treatment-related AEs in Ph1a | From first dose up to 24 months |
| Objective response rate (ORR) | The proportion of participants with best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 in Ph1b | Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first. |
| Duration of response (DOR) | The time interval from first occurrence of a documented objective response to the time of disease progression as determined by the Investigator using RECIST 1.1 or death from any cause, whichever comes first, in Ph1b | Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first. |
| Disease control rate (DCR) | The proportion of participants with a best ORR + Stable Disease (SD) in Ph1b | Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first. |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the concentration curve (AUC0-24) of NPX887 | Measurement of plasma concentration over time for exposure to NPX887 | Following dosing on day 1 of each 21-day treatment cycles up to Cycle 7, then on day 1 every 3 cycles, up to end of treatment and 90-day follow-up |
| Maximum plasma concentration (Cmax) of NPX887 |
Not provided
Inclusion Criteria:
Histologically or cytologically confirmed recurrent, metastatic solid tumor refractory to, or intolerant of, standard of care therapy in one of the following indications:
Phase 1a: Evaluable disease (measurable or non-measurable) by RECIST v.1.1 criteria; Phase 1b: Measurable disease by RECIST v1.1 criteria with additional disease-specific enrollment criteria applied to clear cell RCC, EGFR mutant lung adenocarcinoma, or gastric/GEJ adenocarcinoma.
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
Ability to understand and the willingness to sign a written informed consent document
Willing to use highly effective contraceptive measures throughout the trial.
Exclusion Criteria:
Treatment with any of the following:
Have any unresolved toxicity of ≥Grade 2 from previous anti-cancer treatment, except for alopecia, chronic stable neuropathy for >4 months, changes in skin pigmentation, or requiring replacement therapy for endocrine abnormalities.
Participants with known brain metastases are excluded unless they are clinically stable, with no new or enlarging brain metastases as evidenced on MRI during screening.
History of Grade 3 immune-related pneumonitis or colitis.
Participants who discontinued prior immunotherapy due to immune-related toxicities, or history of unresolved prior immune-related toxicity except for endocrine abnormalities requiring replacement therapy or vitiligo.
Known autoimmune disease requiring immunosuppressive treatment requiring the equivalent of more than 10 mg prednisone daily.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Trials nextpointtx | Contact | (888) 929-NEXT | trials@nextpointtx.com |
| Name | Affiliation | Role |
|---|---|---|
| Leena Gandhi, MD, PhD | NextPoint | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center | Active, not recruiting | Baltimore | Maryland | 21287 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
Dose escalation and dose expansion
Not provided
Not provided
Not provided
Not provided
| Progression-free Survival (PFS) | The duration from the start of treatment until tumor progression or death of any cause in Ph1b | Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first. |
Measurement of plasma concentration over time for exposure to NPX887 |
| Following dosing on day 1 of each 21-day treatment cycles up to Cycle 7, then on day 1 every 3 cycles, up to end of treatment and 90-day follow-up |
| Half-life in blood circulation (T1/2) of NPX887 | Measurement of the clearance of NPX887 from plasma over time | Following dosing on day 1 of each 21-day treatment cycles up to Cycle 7, then on day 1 every 3 cycles, up to end of treatment and 90-day follow-up |
| Immunogenicity of NPX887 | Number of participants with anti-drug antibodies (ADA) | Following dosing on day 1 of each 21-day treatment cycles up to Cycle 4, then on day 1 every 3 cycles, up to 90-day follow-up |
| Overall survival (OS) | Average length of survival for treated participants | From first dose until death from any cause through 24 months |
| Incidence of AEs, DLTs, PD changes within the tumor and in blood | Number of participants with AEs and type, DLTs, and PD changes in Ph1a | From first dose through 21 days, or up to 24 months |
| ORR, DOR, DCR, and PFS | ORR, DOR, DCR, and PFS occur in Ph1a | Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first. |
| Beth Israel Deaconess Medical Center (BIDMC) | Active, not recruiting | Boston | Massachusetts | 02215 | United States |
| Albert Einstein Medical College Montefiore Medical Center | Active, not recruiting | The Bronx | New York | 10461 | United States |
| MD Anderson Cancer Center | Active, not recruiting | Houston | Texas | 77030 | United States |
| Next Oncology | Active, not recruiting | San Antonio | Texas | 78229 | United States |
| NEXT Oncology-Fairfax | Active, not recruiting | Fairfax | Virginia | 22031 | United States |
| Severance Hospital, Yonsei University Health System | Recruiting | Seoul | 03722 | South Korea |
|
| Samsung Medical Center | Recruiting | Seoul | 06351 | South Korea |
|