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.
* 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.
Brief Title
A Study of NPX267 for Subjects With Solid Tumors Known to Express HHLA2/B7-H7
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.
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Metastatic Malignant Neoplasm
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05958199
Org Class
Industry
Org Full Name
NextPoint Therapeutics, Inc.
Org Study Id
NPX267-001
Overall Status
Suspended
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 1a/1b, Dose-Escalation/Dose-Expansion Study of NPX267 in Subjects With Solid Tumors Known to Express HHLA2/B7-H7
Primary Outcomes
Outcome Description
Number of subjects with dose limiting toxicity
Outcome Measure
Incidence of dose limiting toxicity
Outcome Time Frame
from first dose through 21 days
Outcome Description
Number and type of adverse events categorized by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Outcome Measure
Incidence of treatment-emergent adverse events
Outcome Time Frame
up to 12 weeks from first dose
Outcome Description
The proportion of subjects with complete or partial responses or stable disease as defined by RECIST 1.1 criteria
Outcome Measure
Number of subjects with tumor response in tumors expressing B7-H7/HHLA2
Outcome Time Frame
up to 12 weeks from first dose
Secondary Outcomes
Outcome Description
Measurement of plasma concentration over time for exposure to NPX267
Outcome Time Frame
Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
Outcome Measure
Area under the concentration curve (AUC) of NPX267
Outcome Description
Measurement of the clearance of NPX267 from plasma over time
Outcome Time Frame
Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
Outcome Measure
Half-life in circulation (T1/2) of NPX267
Outcome Time Frame
Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
Outcome Measure
Maximum plasma concentration (Cmax) of NPX267
Outcome Description
Average length of survival for treated patients
Outcome Time Frame
From first dose until death from any cause through 30 months
Outcome Measure
Overall survival
Outcome Description
Number of participants with anti-drug antibodies
Outcome Time Frame
From first dose through one year
Outcome Measure
Immunogenicity of NPX267
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404