This pilot phase II trial studies the therapeutic effects and side effects of CD40 agonistic monoclonal antibody APX005M when combined with chemotherapy and radiation therapy, and to see how well they work to reduce or remove esophageal or gastroesophageal (GE) cancers when given before surgery in treating patients with esophageal cancer or GE cancer than can be removed by surgery. APX005M is intended to stimulate the body's own immune system so that the immune cells can more effectively invade and destroy the tumor, adding to the benefits of the chemotherapy and radiation therapy. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving APX005M, chemotherapy, and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Primary Objective: To assess the efficacy of this novel combination, as measured by the pathologic complete response (pCR) rate. Secondary Objectives: 1. To further characterize the safety and feasibility of combining APX005M with SOC chemoradiation (external beam radiation in daily fractions, with concurrent weekly low-dose carboplatin/paclitaxel) in the neoadjuvant setting for patients with resectable esophageal and GE junction cancers. 2. To assess the efficacy of combining APX005M with SOC chemoradiation as measured by rates of R0 resection (microscopically negative margins, i.e., no tumor remains following surgery); and radiographic/metabolic response to neoadjuvant treatment on CT-PET. Exploratory Objectives: 1. To identify possible predictive molecular or immune-based efficacy biomarkers for this novel combination. 2. To characterize and assess overall survival.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
APX005M IV infusion
Radiation therapy, total dose 5040cGy in 180cGy fractions
Paclitaxel IV infusion
Carboplatin IV infusion
Surgical removal of the tumor will occur between weeks 10-17
University of Arizona
Tucson, Arizona, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
University of California, San Francisco
San Francisco, California, United States
MedStar Georgetown University Hospital (MGUH)
Washington D.C., District of Columbia, United States
New York University
New York, New York, United States
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Wake Forest School of Medicine
Winston-Salem, North Carolina, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, United States
Renovatio Clinical
The Woodlands, Texas, United States
University of Washington
Seattle, Washington, United States
Pathologic Complete Response (pCR) Rate (%) Overall
The pCR was defined as post-neoadjuvant pathologic tumour, node, metastasis (ypTNM) (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. * T0: No evidence of primary tumor. * N0: Cancer has not spread to nearby lymph nodes. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
Time frame: At time of surgery, up to a maximum of 261 days
pCR Rate (%) by Baseline Histologic Subgroup
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
Time frame: At time of surgery, up to a maximum of 261 days
pCR Rate (%) by Baseline Tumor Location Subgroup
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
Time frame: At time of surgery, up to a maximum of 261 days
pCR Rate (%) by Steroid Use Subgroup
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. Steroids use: Yes was defined as participants with any steroid (ATC2 class corticosteroids for systemic use) from within 30 days of the first dose of sotigalimab to up to 7 days after the first dose and participants not fulfilling previous requirements are defined as Steroids use: No. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
Time frame: At time of surgery, up to a maximum of 261 days
pCR Rate (%) by Surgery Subgroup
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. The subgroup of participants who had surgery before or at 16/17 weeks were defined as start of study treatment to surgery date from the surgical resection form, less than or equal to 17 weeks (119 days = 17 weeks \* 7 days) or participants who were scheduled to have surgery but had their procedure aborted due to progressive disease at the time of the procedure or immediately before and did not have surgery because of metastasis. The subgroup of participants who had surgery after Week 17 were defined as start of study treatment to surgery date from the surgical resection form, greater than 17 weeks. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
Time frame: At time of surgery, up to a maximum of 261 days
Rate (%) of R0 Resection Overall
R0 was defined as the absence of gross and microscopic tumor involvement in the surgical margins i.e., no tumor remains following surgery. Rate of R0 resection was defined as the percentage of participants who achieved R0 following surgical resection.
Time frame: At time of surgery, up to a maximum of 261 days
Rate (%) of R0 Resection by Baseline Histologic Subgroup
R0 was defined as the absence of gross and microscopic tumor involvement in the surgical margins i.e., no tumor remains following surgery. Rate of R0 resection was defined as the percentage of participants who achieved R0 following surgical resection.
Time frame: At time of surgery, up to a maximum of 261 days
Pathologic Stage at Time of Surgery
Pathologic staging was assessed via ypTNM (after chemoRT and surgery): * Tumor Stage (TX, T0, T1, T1a, T1b, T2, T3, T4, T4a, T4b) refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it had grown into the wall of the esophagus. * Node Stage (NX, N0, N1, N2, N3) refers to the number and location of lymph nodes that cancer has spread to. The higher the number after the N, the more lymph nodes that contained cancer cells. * Metastasis Stage (M0, M1) refers to whether the cancer had not spread (M0) or spread (M1) to other parts of the body. * Stage group (0, I, IA, IB, II, IIA, IIB, III, IIIA, IIIB, IV, IVA, IVB) are based on the TNM stages detailed above. The higher the number, the more advanced the cancer was. For each category, a lower stage/group represents a better outcome.
Time frame: At time of surgery, up to a maximum of 261 days
Radiographic/Metabolic Response to Neoadjuvant Treatment on Computed Tomography (CT)/CT-Positron Emission Tomography (PET) (CT-PET) Overall
Response was adjudicated by the investigator; based on combination of change in wall thickening; size of regional lymph nodes; and metabolic activity of involved areas. As the population does not typically have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST), radiographic/metabolic response was described in qualitative terms (responding/ stable, unchanged/ progressing/ not evaluable).
Time frame: At time of surgery, up to a maximum of 261 days, 3 and 6 months post-operatively, and End of Study Visit (maximum of 6 months post-operatively)
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Radiographic/Metabolic Response to Neoadjuvant Treatment on CT-PET by Baseline Histologic Subgroup
Response was adjudicated by the investigator; based on combination of change in wall thickening; size of regional lymph nodes; and metabolic activity of involved areas. As the population does not typically have measurable disease by RECIST, radiographic/metabolic response was described in qualitative terms (responding/ stable, unchanged/ progressing/ not evaluable).
Time frame: At time of surgery, up to a maximum of 261 days, 3 and 6 months post-operatively, and End of Study Visit (maximum of 6 months post-operatively)
Radiographic/Metabolic Response to Neoadjuvant Treatment on CT-PET by Baseline Tumor Location Subgroup
Response was adjudicated by the investigator; based on combination of change in wall thickening; size of regional lymph nodes; and metabolic activity of involved areas. As the population does not typically have measurable disease by RECIST, radiographic/metabolic response was described in qualitative terms (responding/ stable, unchanged/ progressing/ not evaluable).
Time frame: At time of surgery, up to a maximum of 261 days, 3 and 6 months post-operatively, and End of Study Visit (maximum of 6 months post-operatively)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as adverse events which started on or after the first infusion of study treatment (Carboplatin/Paclitaxel/Sotigalimab/Radiotherapy) until 100 days after receiving the last dose of study treatment, death, or initiation of new anticancer therapy, whichever occurs first. Laboratory values that were considered clinically significant were reported as adverse events.
Time frame: Up to approximately 20 weeks