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

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

Overview

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.

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.

Interventions

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

Primary outcome measures

• Incidence of dose limiting toxicity (DLT) [Time frame: From first dose through 21 days]
• Incidence of treatment-emergent adverse events (AEs) [Time frame: From first dose up to 24 months]
• Incidence of discontinuations, dosing interruptions, and dose reductions [Time frame: From first dose up to 24 months]
• Objective response rate (ORR) [Time frame: Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.]
• Duration of response (DOR) [Time frame: Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.]
• Disease control rate (DCR) [Time frame: Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.]
• Progression-free Survival (PFS) [Time frame: Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.]

Secondary outcome measures (7)

• Area under the concentration curve (AUC0-24) of NPX887 [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]
• Maximum plasma concentration (Cmax) of NPX887 [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]
• Half-life in blood circulation (T1/2) of NPX887 [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]
• Immunogenicity of NPX887 [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]
• Overall survival (OS) [Time frame: From first dose until death from any cause through 24 months]
• Incidence of AEs, DLTs, PD changes within the tumor and in blood [Time frame: From first dose through 21 days, or up to 24 months]
• ORR, DOR, DCR, and PFS [Time frame: Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center — Baltimore
• Beth Israel Deaconess Medical Center (BIDMC) — Boston
• Albert Einstein Medical College Montefiore Medical Center — The Bronx
• MD Anderson Cancer Center — Houston
• Next Oncology — San Antonio
• NEXT Oncology-Fairfax — Fairfax

South Korea · 2 centers

• Severance Hospital, Yonsei University Health System — Seoul
• Samsung Medical Center — Seoul

Identifiers

NCT: NCT06240728 · NPX887-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗