APX005M With Concurrent Chemoradiation for Resectable Esophageal and Gastroesophageal Junction Cancers
- Age ≥ 18 years of age
- Histologically proven squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma of the esophagus or GE junction.
- Surgically resectable (T1-3 Nx by endoscopic ultrasound). Excluded are:
- Very early stage tumors (T1N0)
- Cervical esophageal tumors
- Tumors invading the tracheobronchial tree or associated with tracheoesophageal fistula
- Any evidence of distant metastases (as determined by endoscopic ultrasound (EUS) or CT/PET)
- Cervical, supraclavicular, or other nodal disease that is either not included in the radiation field or is not able to be resected at the time of esophagectomy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Adequate hematological, renal, and hepatic parameters defined as follows:
- Absolute Neutrophil Count (ANC) ≥1.5 × 109/L in absence of growth factor support
- Platelet count ≥150 × 109/L
- Hemoglobin >9 g/dL
- Serum creatinine ≤1.5 mg/dL, or calculated (using the formula of Cockcroft and Gault) or measured creatinine clearance ≥30 mL/min
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN)
- Total bilirubin ≤1.5x ULN
- Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within the 7 days prior to investigational product administration and a negative urine pregnancy test within the 3 days prior to the first investigational product administration, or a negative serum pregnancy test within the 3 days prior to the first investigational product administration
- WOCBP and male subjects who are sexually active with WOCBP must agree to use 2 highly effective methods of contraception (including a physical barrier) during the study and for 30 days following the last dose of investigational product
- Ability to understand a written informed consent document, and the willingness to sign it
- Any history of or current hematologic malignancy
- History of a second primary cancer is allowed in the event the cancer is curatively resected and there is no evidence of recurrence/metastatic disease x 1 year. Subjects who have a history of cervical or breast carcinoma in situ, localized prostate cancer, adequately treated basal cell or squamous cell carcinoma of the skin, or superficial bladder tumors [Ta, Tis & T1] are also allowed
- Major surgery within 4 weeks of first dose of investigational product
- Prior or concurrent treatment with any anticancer agent for the same cancer diagnosis
- Prior exposure to any immuno-oncology agents, including CD40/PD-1/PD-L1/CTLA-4 inhibitors (if any ambiguity, should be discussed with study principal investigator)
- History of bone marrow transplantation
- Uncontrolled diabetes or hypertension
- History of autoimmune disorders with the exception of vitiligo or autoimmune thyroid disorders
- Chronic steroid dependency (prednisone equivalent > 10 mg/day). Any steroid use should be discontinued at least 2 weeks prior to initiation of study treatment.
- History of sensitivity or allergy to monoclonal antibodies (mAbs) or immunoglobulin G (IgG)
- History of severe hypersensitivity reaction to Cremophor EL.
- Pre-existing > grade 2 peripheral sensory neuropathy.
- Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months before first dose
- History of any arterial thromboembolic event within 3 months prior to first dose of investigational product
- Active coagulopathy
- Active known clinically serious infections (> Grade 2 National Cancer Institute (NCI)- CTCAE version 4.03)
- Known human immunodeficiency virus (HIV) infection
- Subjects of reproductive potential who do not use effective methods of birth control
- Pregnant or actively breastfeeding women
- Any clinically significant psychiatric, social, or medical condition that, in the opinion of the Investigator, could increase subject's risk, interfere with protocol adherence, or affect a subject's ability to give informed consent.
PRIMARY OBJECTIVES: I. To establish the safety and feasibility of combining APX005M with standard-of-care chemoradiation (external beam radiation in daily fractions, with concurrent weekly low-dose carboplatin/paclitaxel) in the neoadjuvant setting for patients with resectable esophageal and gastroesophageal junction (GEJ) cancers. SECONDARY OBJECTIVES: I. To assess the efficacy of this novel combination, as measured by the pathologic complete response (pCR) rate. OUTLINE: Patients receive APX005M intravenously (IV) over 60 minutes during weeks 1, 4, and 7, radiation therapy once daily (QD) for 5 days per week during weeks 3-8, and paclitaxel IV over 60 minutes and carboplatin IV over 60 minutes once weekly (days 1, 8, 15, 22, and 29) during weeks 3-8 in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery 4 - 10 weeks after last dose of APX005M. After completion of study treatment, patients are followed up at 1, 3, and 6 months.
Trial Phase Phase II
Trial Type Treatment
- Primary ID APX005M-006
- Secondary IDs NCI-2020-03898
- Clinicaltrials.gov ID NCT03165994