Brief Summary
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:
* what is an appropriate dose to be given to participants?
* are the side effects of treatment manageable?
* what is the preliminary anti-tumor activities?
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.
* what is an appropriate dose to be given to participants?
* are the side effects of treatment manageable?
* what is the preliminary anti-tumor activities?
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.
Brief Title
A Study of NPX887 for Participants With Solid Tumors Known to Express B7-H7/HHLA2
Detailed Description
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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
(888) 929-NEXT
Central Contact Email
trials@nextpointtx.com
Completion Date
Completion Date Type
Estimated
Conditions
Metastatic Malignant Neoplasm
Eligibility Criteria
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 (Dose Escalation): Non-small cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), renal cell carcinoma (RCC), colorectal carcinoma (CRC), gastric and gastro-esophageal carcinoma, esophageal adenocarcinoma, biliary tract cancers, ovarian carcinoma, and other solid tumor types known to express B7-H7/HHLA2.
* Phase 1b including Part 1b (Dose Expansion) and Part 1c (Randomized Dose Comparison): participants who have clear cell RCC, EGFR mutant lung adenocarcinoma, or gastric/GEJ adenocarcinoma.
* In Phase 1b, participants must have confirmed B7-H7/HHLA2 expression in their tumor determined via archival tissue IHC testing through a central lab (pre-screening).
* 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:
* Systemic anticancer treatment ≤14 days or within 5 half-lives prior to the first dose of study drug, whichever is shorter.
* Limited-field radiotherapy ≤7 days or extended-field thoracic radiotherapy ≤8 weeks of the first dose of study drug.
* 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.
* 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 (Dose Escalation): Non-small cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), renal cell carcinoma (RCC), colorectal carcinoma (CRC), gastric and gastro-esophageal carcinoma, esophageal adenocarcinoma, biliary tract cancers, ovarian carcinoma, and other solid tumor types known to express B7-H7/HHLA2.
* Phase 1b including Part 1b (Dose Expansion) and Part 1c (Randomized Dose Comparison): participants who have clear cell RCC, EGFR mutant lung adenocarcinoma, or gastric/GEJ adenocarcinoma.
* In Phase 1b, participants must have confirmed B7-H7/HHLA2 expression in their tumor determined via archival tissue IHC testing through a central lab (pre-screening).
* 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:
* Systemic anticancer treatment ≤14 days or within 5 half-lives prior to the first dose of study drug, whichever is shorter.
* Limited-field radiotherapy ≤7 days or extended-field thoracic radiotherapy ≤8 weeks of the first dose of study drug.
* 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.
Inclusion Criteria
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 (Dose Escalation): Non-small cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), renal cell carcinoma (RCC), colorectal carcinoma (CRC), gastric and gastro-esophageal carcinoma, esophageal adenocarcinoma, biliary tract cancers, ovarian carcinoma, and other solid tumor types known to express B7-H7/HHLA2.
* Phase 1b including Part 1b (Dose Expansion) and Part 1c (Randomized Dose Comparison): participants who have clear cell RCC, EGFR mutant lung adenocarcinoma, or gastric/GEJ adenocarcinoma.
* In Phase 1b, participants must have confirmed B7-H7/HHLA2 expression in their tumor determined via archival tissue IHC testing through a central lab (pre-screening).
* 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.
* 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 (Dose Escalation): Non-small cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), renal cell carcinoma (RCC), colorectal carcinoma (CRC), gastric and gastro-esophageal carcinoma, esophageal adenocarcinoma, biliary tract cancers, ovarian carcinoma, and other solid tumor types known to express B7-H7/HHLA2.
* Phase 1b including Part 1b (Dose Expansion) and Part 1c (Randomized Dose Comparison): participants who have clear cell RCC, EGFR mutant lung adenocarcinoma, or gastric/GEJ adenocarcinoma.
* In Phase 1b, participants must have confirmed B7-H7/HHLA2 expression in their tumor determined via archival tissue IHC testing through a central lab (pre-screening).
* 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.
Gender
All
Gender Based
false
Keywords
B7-H7
HHLA2
solid tumor malignancies
monoclonal antibody
Dose escalation
Dose expansion
RECIST
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06240728
Org Class
Industry
Org Full Name
NextPoint Therapeutics, Inc.
Org Study Id
NPX887-001
Overall Status
Recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 1a/1b Dose Escalation and Dose Expansion Study of NPX887 in Participants With Solid Tumor Malignancies Known to Express B7-H7/HHLA2
Primary Outcomes
Outcome Description
Number of participants with DLT in Ph1a
Outcome Measure
Incidence of dose limiting toxicity (DLT)
Outcome Time Frame
From first dose through 21 days
Outcome Description
Number and type of AEs categorized by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 in Ph1a
Outcome Measure
Incidence of treatment-emergent adverse events (AEs)
Outcome Time Frame
From first dose up to 24 months
Outcome Description
Number of participants with changes to their dosing schedule as a result of treatment-related AEs in Ph1a
Outcome Measure
Incidence of discontinuations, dosing interruptions, and dose reductions
Outcome Time Frame
From first dose up to 24 months
Outcome Description
The proportion of participants with best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 in Ph1b
Outcome Measure
Objective response rate (ORR)
Outcome Time Frame
Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
Outcome Description
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
Outcome Measure
Duration of response (DOR)
Outcome Time Frame
Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
Outcome Description
The proportion of participants with a best ORR + Stable Disease (SD) in Ph1b
Outcome Measure
Disease control rate (DCR)
Outcome Time Frame
Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
Outcome Description
The duration from the start of treatment until tumor progression or death of any cause in Ph1b
Outcome Measure
Progression-free Survival (PFS)
Outcome Time Frame
Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
Secondary Outcomes
Outcome Description
Measurement of plasma concentration over time for exposure to NPX887
Outcome Time Frame
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
Outcome Measure
Area under the concentration curve (AUC0-24) of NPX887
Outcome Description
Measurement of plasma concentration over time for exposure to NPX887
Outcome Time Frame
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
Outcome Measure
Maximum plasma concentration (Cmax) of NPX887
Outcome Description
Measurement of the clearance of NPX887 from plasma over time
Outcome Time Frame
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
Outcome Measure
Half-life in blood circulation (T1/2) of NPX887
Outcome Description
Number of participants with anti-drug antibodies (ADA)
Outcome Time Frame
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
Outcome Measure
Immunogenicity of NPX887
Outcome Description
Average length of survival for treated participants
Outcome Time Frame
From first dose until death from any cause through 24 months
Outcome Measure
Overall survival (OS)
Outcome Description
Number of participants with AEs and type, DLTs, and PD changes in Ph1a
Outcome Time Frame
From first dose through 21 days, or up to 24 months
Outcome Measure
Incidence of AEs, DLTs, PD changes within the tumor and in blood
Outcome Description
ORR, DOR, DCR, and PFS occur in Ph1a
Outcome Time Frame
Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
Outcome Measure
ORR, DOR, DCR, and PFS
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404