A Study of EMB-09 in Participants With Advanced or Metastatic Solid Tumors.

A First-in-human, Phase I Trial of EMB-09, a Bispecific Antibody Targeting PD-L1 and OX-40 in Patients With Advanced or Metastatic Solid Tumors

This study is to evaluate the safety and tolerability of EMB-09 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Pharmacokinetics (PK), immunogenicity, and the anti-multiple myeloma activity of EMB-09 will also be assessed.

This is a phase I, multi-center, open label, multiple dose, first in human study, designed to assess safety and tolerability, and to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose for EMB-09 in patient with advanced or metastatic solid tumors. Pharmacokinetics,pharmacodynamics, immunogenicity and response will also be assessed.

Inclusion Criteria:

• Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures.

• Phase I subjects:

  1. Patients with histologically or cytologically confirmed locally advanced/metastatic solid tumors including but not limited to melanoma, non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), head and neck squamous cell carcinoma (HNSCC), nasopharyngeal cancer (NPC), hepatocellular carcinoma (HCC), gastric cancer (GC), endometrium cancer (EC), ovarian cancer (OC), renal cell carcinoma (RCC) and small cell lung cancer (SCLC), colorectal cancer (CRC).
  2. Patients who have failed (progressed on, or are intolerant of) standard therapies or no available standard treatment
  3. Measurable or evaluable disease per RECIST v1.1.

• Patients must provide archival tumor, or a fresh tumor biopsy will be required if archival tumor sample is not available. Archival tumor sample must be taken <2 years prior to screening, otherwise a fresh tumor biopsy at screening is required.

• ECOG performance status 0 or 1; life expectancy > 3 months.

• Adequate organ function to participate in the trial.

• Recovery from adverse events (AEs) related to prior anticancer therapy.

• Highly effective contraception

Exclusion Criteria:

• Patients who have active autoimmune disease or history of autoimmune disease
• History of severe irAE.
• History of severe allergic reactions
• Use of systemic corticosteroids.
• Symptomatic central nervous system metastases.
• Patients with cardiac dysfunction
• Uncontrolled diabetes mellitus with hemoglobin A1c > 8% (via medical history)
• Prior treatment with TNFRSF agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR), CD40.
• Anticancer therapy or radiation < 5 half-lives or 4 weeks (whichever is shorter) prior to study treatment;
• Current or history of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia.
• Concurrent malignancy < 5 years prior to entry.
• Patients with active infections.
• Major surgery < 4 weeks or minor surgery < 2 weeks prior to study treatment.
• Live virus vaccines < 30 days prior to screening
• Pregnant or breast-feeding females
• Any investigational agents or study drugs from a previous clinical study within 30 days of the first dose of study treatment.
• Any other serious underlying medical conditions
• Abuse of alcohol, cannabis-derived products, or other drugs.