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Completed

NCT Number: NCT03165994

APX005M With Concurrent Chemoradiation for Resectable Esophageal and Gastroesophageal Junction Cancers

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.

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Key information

Conditions

Esophageal Cancer Digestive System Diseases Digestive System Neoplasms Esophageal Diseases Esophageal Neoplasms GastroEsophageal Cancer Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms Neoplasms Neoplasms by Site

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Arizona, Tucson, Arizona, United States

Loading trial locations.

About this study

Primary Objective:

To assess the efficacy of this novel combination, as measured by the pathologic complete response (pCR) rate.

Secondary Objectives:

  • 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.
  • 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:

  • To identify possible predictive molecular or immune-based efficacy biomarkers for this novel combination.
  • To characterize and assess overall survival.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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 preferably by endoscopic ultrasound [EUS]). (Excluded: T1N0 tumors, cervical esophageal location, tumors invading the tracheobronchial tree or with fistula, distant disease that cannot be included in the radiation field or be resected at the time of esophagectomy).
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Adequate hematological, renal, and hepatic parameters.

Exclusion criteria

  • 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.
  • 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.
  • 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.
  • Known human immunodeficiency virus (HIV) infection.

Treatment and study plan

APX005M

Drug

APX005M IV infusion

Other names: CD40 Agonistic Monoclonal Antibody, PYX-107, Sotigalimab

radiation therapy

Radiation

Radiation therapy, total dose 5040cGy in 180cGy fractions

Other names: Radiotherapy

paclitaxel

Drug

Paclitaxel IV infusion

Other names: Taxol

carboplatin

Drug

Carboplatin IV infusion

Other names: Paraplatin

Surgical resection of tumor

Procedure

Surgical removal of the tumor will occur between weeks 10-17

Other names: Surgery, Operation

Primary outcomes

  1. Pathologic Complete Response (pCR) Rate (%) Overall

    Time frame: At time of surgery, up to a maximum of 261 days

    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%.

  2. pCR Rate (%) by Baseline Histologic Subgroup

    Time frame: At time of surgery, up to a maximum of 261 days

    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%.

  3. pCR Rate (%) by Baseline Tumor Location Subgroup

    Time frame: At time of surgery, up to a maximum of 261 days

    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%.

  4. pCR Rate (%) by Steroid Use Subgroup

    Time frame: At time of surgery, up to a maximum of 261 days

    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%.

  5. pCR Rate (%) by Surgery Subgroup

    Time frame: At time of surgery, up to a maximum of 261 days

    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%.

Secondary outcomes

  1. Rate (%) of R0 Resection Overall

    Time frame: At time of surgery, up to a maximum of 261 days

    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.

  2. Rate (%) of R0 Resection by Baseline Histologic Subgroup

    Time frame: At time of surgery, up to a maximum of 261 days

    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.

  3. Pathologic Stage at Time of Surgery

    Time frame: At time of surgery, up to a maximum of 261 days

    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.

  4. Radiographic/Metabolic Response to Neoadjuvant Treatment on Computed Tomography (CT)/CT-Positron Emission Tomography (PET) (CT-PET) Overall

    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)

    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).

  5. Radiographic/Metabolic Response to Neoadjuvant Treatment on CT-PET by Baseline Histologic Subgroup

    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)

    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).

  6. Radiographic/Metabolic Response to Neoadjuvant Treatment on CT-PET by Baseline Tumor Location Subgroup

    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)

    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).

  7. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Time frame: Up to approximately 20 weeks

    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.

Sponsors and collaborators

Lead sponsor

Apexigen America, Inc.

Industry

Registry information

Official study title

A Phase 2 Study of APX005M in Combination With Concurrent Chemoradiation as Neoadjuvant Therapy for Resectable Esophageal and Gastroesophageal Junction Cancers

Important dates

Study start
2017
Primary completion
2022
Study completion
2023
First posted
May 24, 2017
Registry last updated
May 2, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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