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

Metastatic Malignant Neoplasm Clinical Trial

Official title:

A Phase 1a/1b Dose Escalation and Dose Expansion Study of NPX887 in Participants With Solid Tumor Malignancies Known to Express HHLA-2/B7-H7

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06240728
• Other study ID #: NPX887-001
• Status: Recruiting
• Phase: Phase 1
• Start date: January 22, 2024
• Est. completion date: August 2027

Study information

• Verified date: April 2024
• Source: NextPoint Therapeutics, Inc.
• Contact: Leena Gandhi, MD, PhD
• Phone: 857 209-0486
• Email: NPX887-001[@]nextpointtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

NPX887 is a human, antagonistic immunoglobulin G1 (IgG1) monoclonal antibody targeting HHLA2 (B7-H7) 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 in participants whose cancers are known to express HHLA2 (B7-H7).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? 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.

Description:

This study is comprised of Phase 1a (Dose Escalation) and Phase 1b (Dose Expansion). 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 activity in multiple disease-specific cohorts and compare the efficacy of the higher and lower doses chosen in Phase 1a. Throughout the study, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: August 2027
• Est. primary completion date: August 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed recurrent, metastatic solid tumor refractory

to standard of care therapy in one of the following indications:

• Phase 1a: Non-small cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), renal cell carcinoma (RCC), colorectal carcinoma (CRC), and other solid tumor types known to express HHLA2/B7-H7.
• Phase 1b: participants who have clear cell RCC, lung adenocarcinoma, or CRC.
• In Phase 1b, participants must have confirmed HHLA2/B7-H7 expression in their tumor.
• Phase 1a: Evaluable disease (measurable or non-measurable) by RECIST v.1.1 criteria; Phase 1b: Measurable disease by RECIST v1.1 criteria.
• 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 prior to the first dose of study drug.
• Limited-field radiotherapy <7 days or extended-field thoracic radiotherapy <8 weeks of the first dose of study drug.
• 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.

Related Conditions & MeSH terms

• Metastatic Malignant Neoplasm
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center (BIDMC)	Boston	Massachusetts
United States	NEXT Oncology-Fairfax	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	Next Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
NextPoint Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicity (DLT)	Number of participants with DLT	From first dose through 21 days
Primary	Incidence of treatment-emergent adverse events (AEs)	Number and type of AEs categorized by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Up to 24 months from first dose
Primary	Incidence of discontinuations, dosing interruptions, and dose reductions	Number of participants with changes to their dosing schedule as a result of treatment-related AEs	From first dose up to 24 months
Secondary	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
Secondary	Maximum plasma concentration (Cmax) 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
Secondary	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
Secondary	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
Secondary	Overall survival (OS)	Average length of survival for treated participants	From first dose until death from any cause through 24 months