A Study of NPX267 for Subjects With Solid Tumors Known to Express HHLA2/B7-H7

Metastatic Malignant Neoplasm Clinical Trial

Official title:

A Phase 1a/1b, Dose-Escalation/Dose-Expansion Study of NPX267 in Subjects With Solid Tumors Known to Express HHLA2/B7-H7

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05958199
• Other study ID #: NPX267-001
• Status: Recruiting
• Phase: Phase 1
• Start date: July 21, 2023
• Est. completion date: January 2026

Study information

• Verified date: January 2024
• Source: NextPoint Therapeutics, Inc.
• Contact: Leena Gandhi, MD, PhD
• Phone: 857 209-0486
• Email: NPX267-001[@]nextpointtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

NPX267 is an antibody drug targeting the inhibitory receptor for B7-H7 (HHLA2) which may control evasion of the immune response in tumors. The goal of this clinical trial is to learn whether NPX267 is safe and tolerable in patients whose cancers are known to express HHLA2 including epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer. The main questions it aims to answer are:

• what is an appropriate dose to be given to patients?

• are the side effects of treatment manageable?

Participants will be evaluated for participation in the study. Patients who are treated will receive an intravenous infusion of NPX267 every three weeks if their disease has not progressed. Patients will be closely monitored by the treating physician.

Description:

This trial is divided into two parts. The first part (dose escalation) will test different doses of drug to find a dose for part two. In the second part (dose expansion), more patients will be tested to see if the drug has an effect on patient's tumors.

Throughout the study, data will be collected to characterize the clinical activity of the drug. Samples of blood will be taken to help in an understanding of how the drug behaves in the body by assessing the amount of drug in the blood over time (pharmacokinetics), and changes in blood components (pharmacodynamics and safety). Tumor imaging by computed tomography (CT) or magnetic resonance imaging (MRI) will be done about every nine weeks to assess NPX267 impact on tumor growth.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 131
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• 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: Part 1a: non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), colorectal carcinoma (CRC), cholangiocarcinoma (CCA), pancreatic cancer (PDAC), urothelial carcinoma (UCC), gastric/gastroesophageal carcinoma, triple negative breast carcinoma, endometrial carcinoma, cervical cancer, osteosarcoma, and prostate cancer

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Normal bone marrow, kidney and liver function

• Willing to use highly effective contraceptive measures throughout the trial

Exclusion Criteria:

• Have any unresolved toxicity of Grade = 2 from previous anti-cancer treatment, except for alopecia, chronic neuropathy > 6 months, or changes in skin pigmentation

• Have known or suspected brain metastases, unless they are clinically stable

• Known autoimmune disease requiring immunosuppressive treatment requiring the equivalent of more than 10 mg prednisone daily

• History of grade 3 immune-related pneumonitis or colitis

Related Conditions & MeSH terms

• Metastatic Malignant Neoplasm
• Neoplasms

Intervention

Drug:
• NPX267
NPX267 will be administered by intravenous infusion every three weeks until documented disease progression or participant withdrawal

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	NEXT Oncology-Fairfax	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Albert Einstein Medical College	New York	New York
United States	NEXT Oncology-San Antonio	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
Other	Change in biomarkers of activity	Exploratory analysis of biomarkers from collected tumor and blood samples	From first dose through one year
Primary	Incidence of dose limiting toxicity	Number of subjects with dose limiting toxicity	from first dose through 21 days
Primary	Incidence of treatment-emergent adverse events	Number and type of adverse events categorized by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	up to 12 weeks from first dose
Primary	Number of subjects with tumor response in tumors expressing B7-H7/HHLA2	The proportion of subjects with complete or partial responses or stable disease as defined by RECIST 1.1 criteria	up to 12 weeks from first dose
Secondary	Area under the concentration curve (AUC) of NPX267	Measurement of plasma concentration over time for exposure to NPX267	Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
Secondary	Half-life in circulation (T1/2) of NPX267	Measurement of the clearance of NPX267 from plasma over time	Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
Secondary	Maximum plasma concentration (Cmax) of NPX267		Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
Secondary	Overall survival	Average length of survival for treated patients	From first dose until death from any cause through 30 months
Secondary	Immunogenicity of NPX267	Number of participants with anti-drug antibodies	From first dose through one year