Clinical trial NCT06240728: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Malignant Neoplasm
Keywords: B7-H7
HHLA2
solid tumor malignancies
monoclonal antibody
Dose escalation
Dose expansion
RECIST
Lead sponsor: NextPoint Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-02-05
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Dose escalation and dose expansion
Primary purpose: TREATMENT

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.

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.

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.
* Fresh tissue biopsies: Participants in Cohorts 2 and above in Phase 1a, the first 10 participants in each cohort of Part 1b, and the first 5 participants at each dose level in Part 1c cohort(s) will be required to have sufficient and adequate tumor tissue samples for a fresh screening biopsy and a mandatory on-treatment biopsy as clinically feasible.
* 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.

Primary outcomes:
measure: Incidence of dose limiting toxicity (DLT)
timeFrame: From first dose through 21 days
measure: Incidence of treatment-emergent adverse events (AEs)
timeFrame: From first dose up to 24 months
measure: Incidence of discontinuations, dosing interruptions, and dose reductions
timeFrame: From first dose up to 24 months
measure: Objective response rate (ORR)
timeFrame: Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
measure: Duration of response (DOR)
timeFrame: Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
measure: Disease control rate (DCR)
timeFrame: Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
measure: Progression-free Survival (PFS)
timeFrame: Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
Secondary outcomes:
measure: Area under the concentration curve (AUC0-24) of NPX887
timeFrame: 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
measure: Maximum plasma concentration (Cmax) of NPX887
timeFrame: 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
measure: Half-life in blood circulation (T1/2) of NPX887
timeFrame: 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
measure: Immunogenicity of NPX887
timeFrame: 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
measure: Overall survival (OS)
timeFrame: From first dose until death from any cause through 24 months
measure: Incidence of AEs, DLTs, PD changes within the tumor and in blood
timeFrame: From first dose through 21 days, or up to 24 months
measure: ORR, DOR, DCR, and PFS
timeFrame: Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (BIDMC)
state: Massachusetts
city: Bronx
country: United States
facility: Albert Einstein Medical College Montefiore Medical Center
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology-Fairfax
state: Virginia
Study officials:
affiliation: NextPoint
name: Leena Gandhi, MD, PhD
role: STUDY_DIRECTOR
References: