Overview
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.
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.