A Study of NPX887 for Participants With Solid Tumors Known to Express B7-H7/HHLA2

NCT06240728 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NPX887-001
• Study Type: interventional
• Target: 144
• Locations: 2 countries
• Sites: 8

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.

Conditions

Metastatic Malignant Neoplasm

Keywords

B7-H7; HHLA2; solid tumor malignancies; monoclonal antibody; Dose escalation; Dose expansion; RECIST

Outcome Measures

Primary Outcomes (7)

• 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.

• 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.

Secondary Outcomes (7)

• Area under the concentration curve (AUC0-24) of 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

  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

  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

  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)

  From first dose until death from any cause through 24 months

Study Arms (1)

NPX887 Treatment

EXPERIMENTAL

Participants will receive NPX887 by IV infusion every 3 weeks.

Drug: NPX887

Interventions

NPX887 DRUG

NPX887 will be administered by IV infusion every 3 weeks until documented disease progression or participant withdrawal for up to 2 years

NPX887 Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• NextPoint Therapeutics, Inc.: lead

Study Sites (8)

Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

ACTIVE NOT RECRUITING

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States

ACTIVE NOT RECRUITING

Albert Einstein Medical College Montefiore Medical Center

The Bronx, New York, 10461, United States

ACTIVE NOT RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

Next Oncology

San Antonio, Texas, 78229, United States

ACTIVE NOT RECRUITING

NEXT Oncology-Fairfax

Fairfax, Virginia, 22031, United States

ACTIVE NOT RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Leena Gandhi, MD, PhD

  NextPoint

  STUDY DIRECTOR

Central Study Contacts

Trials nextpointtx

CONTACT

(888) 929-NEXT; trials@nextpointtx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation and dose expansion

Study Record Dates

• First Submitted: January 26, 2024
• First Posted: February 5, 2024
• Study Start: January 22, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); KR (2)