A Study of NPX267 for Subjects With Solid Tumors Known to Express HHLA-2

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1a/1b, Dose-Escalation/Dose-Expansion Study of NPX267 in Subjects With Solid Tumors Known to Express HHLA-2

Conditions
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Metastatic Malignant Neoplasm

Intervention / Treatment
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* Drug: NPX267


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Dose escalation and dose expansion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPX267 Treatment<br> | Drug: NPX267<br>* NPX267 will be administered by intravenous infusion every three weeks until documented disease progression or participant withdrawal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicity | Number of subjects with dose limiting toxicity | from first dose through 21 days | 
| 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 | 
| Number of subjects with tumor response in tumors expressing 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| Maximum plasma concentration (Cmax) of NPX267 |  | Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles) | 
| Overall survival | Average length of survival for treated patients | From first dose until death from any cause through 30 months | 
| Immunogenicity of NPX267 | Number of participants with anti-drug antibodies | From first dose through one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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