Clinical trial NCT05958199: A Study of NPX267 for Subjects With Solid Tumors Known to Express HHLA2/B7-H7
Official title: A Phase 1a/1b, Dose-Escalation/Dose-Expansion Study of NPX267 in Subjects With Solid Tumors Known to Express HHLA2/B7-H7
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Malignant Neoplasm
Keywords: B7-H7/HHLA2
Non-small cell lung carcinoma
renal cell carcinoma
colorectal carcinoma
cholangiocarcinoma
pancreatic cancer
urothelial carcinoma
gastric gastroesophageal carcinoma
triple negative breast carcinoma
endometrial carcinoma
cervical cancer
osteosarcoma
prostate cancer
RECIST
Dose escalation
Dose expansion
Lead sponsor: NextPoint Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-07-24
Enrollment: 131
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: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of dose limiting toxicity
timeFrame: from first dose through 21 days
measure: Incidence of treatment-emergent adverse events
timeFrame: up to 12 weeks from first dose
measure: Number of subjects with tumor response in tumors expressing B7-H7/HHLA2
timeFrame: up to 12 weeks from first dose
Secondary outcomes:
measure: Area under the concentration curve (AUC) of NPX267
timeFrame: Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
measure: Half-life in circulation (T1/2) of NPX267
timeFrame: Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
measure: Maximum plasma concentration (Cmax) of NPX267
timeFrame: Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
measure: Overall survival
timeFrame: From first dose until death from any cause through 30 months
measure: Immunogenicity of NPX267
timeFrame: From first dose through one year
Other outcomes:
measure: Change in biomarkers of activity
timeFrame: From first dose through one year
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Albert Einstein Medical College Montefiore Medical Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology-San Antonio
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: