APX005M With Concurrent Chemoradiation for Resectable Esophageal and Gastroesophageal Junction Cancers

NCT ID: NCT03165994

Last Updated: 2024-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-06
• Study Completion Date: 2023-02-21

Brief Summary

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.

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.

Conditions

Esophageal Cancer; GastroEsophageal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

APX005M

Intervention Type: DRUG

APX005M IV infusion

Radiation Therapy

Intervention Type: RADIATION

Radiation therapy, total dose 5040cGy in 180cGy fractions

Paclitaxel

Intervention Type: DRUG

Paclitaxel IV infusion

Carboplatin

Intervention Type: DRUG

Carboplatin IV infusion

Surgical resection of tumor

Intervention Type: PROCEDURE

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

Interventions

APX005M

APX005M IV infusion

Intervention Type: DRUG

Radiation Therapy

Radiation therapy, total dose 5040cGy in 180cGy fractions

Intervention Type: RADIATION

Paclitaxel

Paclitaxel IV infusion

Intervention Type: DRUG

Carboplatin

Carboplatin IV infusion

Intervention Type: DRUG

Surgical resection of tumor

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

Intervention Type: PROCEDURE

Other Intervention Names

CD40 Agonistic Monoclonal Antibody; PYX-107; Sotigalimab; Radiotherapy; Taxol; Paraplatin; Surgery; Operation

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Apexigen America, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Countries

United States

References

Ko AH, Chao J, Noel MS, Shankaran V, Sohal D, Crow M, Oberstein PE, Scott AJ, McRee AJ, Rocha Lima CMSP, Fong L, Keenan BP, Soto M, Filbert EL, Hsu FJ, Yang X. A Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers. Cancer Res Commun. 2025 Feb 1;5(2):349-357. doi: 10.1158/2767-9764.CRC-24-0513.

Reference Type: DERIVED

PMID: 39907035 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

APX005M-006

Identifier Type: -

Identifier Source: org_study_id