APX005M With Concurrent Chemoradiation for Resectable Esophageal and Gastroesophageal Junction Cancers

April 4, 2024 updated by: Apexigen America, Inc.

A Phase 2 Study of APX005M in Combination With Concurrent Chemoradiation as Neoadjuvant Therapy 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
34

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • University of Arizona
    • California
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • District of Columbia
      • Washington, District of Columbia, United States, 20007-2113
        • MedStar Georgetown University Hospital (MGUH)
    • New York
      • New York, New York, United States, 10016
        • New York University
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7305
        • The University of North Carolina at Chapel Hill
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest School of Medicine
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Medical Center
    • Texas
      • The Woodlands, Texas, United States, 77380
        • Renovatio Clinical
    • Washington
      • Seattle, Washington, United States, 98109
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years of age.
  2. Histologically proven squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma of the esophagus or GE junction.
  3. 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).
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  5. Adequate hematological, renal, and hepatic parameters.

Exclusion Criteria:

  1. Any history of or current hematologic malignancy.
  2. 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.
  3. Major surgery within 4 weeks of first dose of investigational product.
  4. Prior or concurrent treatment with any anticancer agent for the same cancer diagnosis.
  5. 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).
  6. History of bone marrow transplantation.
  7. History of autoimmune disorders with the exception of vitiligo or autoimmune thyroid disorders.
  8. Chronic steroid dependency (prednisone equivalent > 10 mg/day). Any steroid use should be discontinued at least 2 weeks prior to initiation of study treatment.
  9. 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.
  10. Known human immunodeficiency virus (HIV) infection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: APX005M With Standard of Care Chemoradiation

Participants will receive standard of care chemoradiation, consisting of:

  • External beam radiation in daily fractions (28 fractions) from Weeks 1-6, administered once per day up to 5 days/week.
  • Carboplatin (area under the carboplatin plasma concentration versus time curve = 2) and paclitaxel (50 mg/m^2) chemotherapy intravenously (IV) over 1 hour, once weekly, from Weeks 1-5.

The participants also will receive concurrent 0.3 mg/kg APX005M IV over 1 hour, once weekly, on Weeks 1, 2, 4, and 6 (2-3 days after chemoradiation).

Surgical resection of the tumor will be planned from Week 10 up to approximately Week 17, as indicated in the protocol amendment under which each participant is enrolled.
Drug: Carboplatin
Carboplatin IV infusion
Other Names:
  • Paraplatin
Radiation: Radiation Therapy
Radiation therapy, total dose 5040cGy in 180cGy fractions
Other Names:
  • Radiotherapy
Drug: Paclitaxel
Paclitaxel IV infusion
Other Names:
  • Taxol
Drug: APX005M
APX005M IV infusion
Other Names:
  • CD40 Agonistic Monoclonal Antibody
  • PYX-107
  • Sotigalimab
Procedure: Surgical resection of tumor
Surgical removal of the tumor will occur between weeks 10-17
Other Names:
  • Operation
  • Surgery

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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%.
At time of surgery, up to a maximum of 261 days
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%.
At time of surgery, up to a maximum of 261 days
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%.
At time of surgery, up to a maximum of 261 days
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%.
At time of surgery, up to a maximum of 261 days
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%.
At time of surgery, up to a maximum of 261 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
At time of surgery, up to a maximum of 261 days
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.
At time of surgery, up to a maximum of 261 days
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.
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
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).
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 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).
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
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).
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)
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.
Up to approximately 20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Apexigen America, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 6, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 10, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 21, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 23, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 23, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 24, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 2, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APX005M-006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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