APX005M With Concurrent Chemoradiation for Resectable Esophageal and Gastroesophageal Junction Cancers

NCT03165994 | Completed Phase 2 Results FDA Drug

• 1 other identifier: APX005M-006
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 10

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.

Conditions

Esophageal Cancer; GastroEsophageal Cancer

Keywords

esophagus; gastroesophageal junction; T1-3N0-1; GE junction

Outcome Measures

Primary Outcomes (5)

• 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%.

  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%.

  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%.

  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%.

  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%.

  At time of surgery, up to a maximum of 261 days

Secondary Outcomes (7)

• Rate (%) of R0 Resection Overall

  At time of surgery, up to a maximum of 261 days

• Rate (%) of R0 Resection by Baseline Histologic Subgroup

  At time of surgery, up to a maximum of 261 days

• Pathologic Stage at Time of Surgery

  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

  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

  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)

Study Arms (1)

APX005M With Standard of Care Chemoradiation

EXPERIMENTAL

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: APX005M; Radiation: Radiation Therapy; Drug: Paclitaxel; Drug: Carboplatin; Procedure: Surgical resection of tumor

Interventions

APX005M DRUG

APX005M IV infusion

Also known as: CD40 Agonistic Monoclonal Antibody, PYX-107, Sotigalimab

APX005M With Standard of Care Chemoradiation

Radiation Therapy RADIATION

Radiation therapy, total dose 5040cGy in 180cGy fractions

Also known as: Radiotherapy

APX005M With Standard of Care Chemoradiation

Paclitaxel DRUG

Paclitaxel IV infusion

Also known as: Taxol

APX005M With Standard of Care Chemoradiation

Carboplatin DRUG

Carboplatin IV infusion

Also known as: Paraplatin

APX005M With Standard of Care Chemoradiation

Surgical resection of tumor PROCEDURE

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

Also known as: Surgery, Operation

APX005M With Standard of Care Chemoradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Apexigen America, Inc.: lead

Study Sites (10)

University of Arizona

Tucson, Arizona, 85719, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MedStar Georgetown University Hospital (MGUH)

Washington D.C., District of Columbia, 20007-2113, United States

Location

New York University

New York, New York, 10016, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7305, United States

Location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Renovatio Clinical

The Woodlands, Texas, 77380, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 39907035 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

sotigalimab; Radiotherapy; Paclitaxel; Carboplatin; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Pyxis Oncology Clinical Operations
• Organization: Pyxis Oncology, Inc.

clinicaltrials@pyxisoncology.com

(339) 545 8252

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Non-comparative, open-label pilot study

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: May 24, 2017
• Study Start: October 6, 2017
• Primary Completion: November 10, 2022
• Study Completion: February 21, 2023
• Last Updated: May 2, 2024
• Results First Posted: May 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)