Safety, Tolerability and Pharmacokinetics of an Anti-PD-1 Monoclonal Antibody in Subjects With Advanced Malignancies

NCT03474640 | Completed Phase 1 Results FDA Drug

• 1 other identifier: TAB001-01
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 14

Brief Summary

The primary objective is to assess the safety and tolerability of Toripalimab in subjects with various advanced malignancies and to evaluate the recommended Phase 2 dose. The secondary objectives are to: 1) describe the pharmacokinetic (PK) profile of Toripalimab, 2) evaluate antitumor activity of Toripalimab; 3) determine the immunogenicity of Toripalimab; 4) evaluate overall survival. The exploratory objectives are to: 1) evaluate biomarkers that may correlate with activity of Toripalimab, 2) evaluate pharmacodynamic effects of Toripalimab on its target receptor, programmed cell death 1 (PD-1), as well as effects on the immune system. 3) evaluate the utility of PD-L1 \& additional exploratory markers as biomarkers that could aid in selection of appropriate subjects for TAB001 therapy, and 4) identification of additional biomarkers correlating with response to treatment with TAB001.

Conditions

Advanced Malignancies

Keywords

immunotherapy; check point inhibitor; PD-1 antibody; solid tumor; esophageal carcinoma; gastric carcinoma; nasopharyngeal carcinoma; hepatocellular carcinoma; soft tissue sarcoma; chondrosarcoma; orphan tumors; phase 1 trial

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

  To assess the number of treatment-related adverse events in the toripalimab arm as assessed by CTCAE v4.0

  Through study completion, an estimated period of approximately 2 years.

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Every 8 weeks (Part A) or every 9 weeks (Part B) through study completion, an estimated duration of 2 years.

• Disease Control Rate (DCR)

  Every 8 weeks (Part A) or every 9 weeks (Part B) through study completion, an estimated duration of 2 years.

• Progression-Free Survival (PFS)

  Every 8 weeks (Part A) or every 9 weeks (Part B) through study completion, an estimated duration of 2 years.

• Overall Survival (OS)

  Through study completion, an estimated duration of 2 years.

Study Arms (2)

Part A

EXPERIMENTAL

Sequential dose escalation (3+3)

Biological: Part A

Part B

EXPERIMENTAL

Indication specific dose cohorts: Esophageal Cancer, Gastric Cancer/GEJ, Biliary Tract Cancer, Soft Tissue Sarcoma (excluding Leiomyosarcoma) or Chondrosarcoma, Neuroendocrine Cancer, and other tumors (including Nasopharyngeal Cancer (NPC), Hepatocellular Carcinoma (HCC), MSI-H/dMMR tumors).

Biological: Part B

Interventions

Part A BIOLOGICAL

Part A: 80, 240, and 480 mg IV every 14 days.

Also known as: Toripalimab, TAB001, JS001

Part A

Part B BIOLOGICAL

Part B: 240 mg IV every 3 weeks

Also known as: Toripalimab, TAB001, JS001

Part B

Eligibility Criteria

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

You may qualify if:

• Willing to sign Informed Consent;
• Part A, must have a histologically or cytologically documented, incurable, or metastatic solid tumor that has progressed on, or been intolerant to, all standard systemic therapy options for the tumor type in the metastatic setting, or must have a tumor type for which no such standard systemic option exists;
• Part B, must have a histologically or cytologically documented diagnosis of esophageal or gastric carcinoma, nasopharyngeal carcinoma (NPC), hepatocellular carcinoma (HCC), both soft tissue sarcoma (excluding leiomyosarcoma), chondrosarcoma, or with agreement of the sponsor, or other tumors who have received at least one line of standard systemic therapy for their respective tumor type in the metastatic setting with progressive locally advanced or metastatic disease that is not amenable to definitive local therapy with curative intent. Patient with MSI-H/dMMR Tumors are eligible to enroll.
• Subjects with NPC must have received, or been intolerant to, a platinum-based combination as part of their prior therapy for advanced/metastatic disease;
• Subjects with soft tissue sarcoma and chondrosarcoma must have radiographic evidence of progression within the previous 6 months and must have received at least 1 line of systemic therapy;
• Subjects with esophageal cancer must have received, or been intolerant to, a platinum-based combination as part of their prior therapy for advanced/metastatic disease;
• Subjects with gastric cancer must have received, or been intolerant to, a fluoropyrimidine-platinum combination as part of their prior therapy for advanced/metastatic disease;
• Subjects with HCC must have received (or been intolerant to) sorafenib as part of their prior therapy for advanced metastatic disease.
• Measurable disease per RECIST v1.1 and irRECIST;
• ECOG performance status of 0 or 1;
• Adequate organ and marrow function;
• Willingness to provide consent for biopsy samples;
• For females of childbearing potential, use effective contraception from time of screening though 90 days post last dose of Toripalimab.

You may not qualify if:

• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study;
• Any concurrent chemotherapy, radiotherapy, immunotherapy, or biologic therapy for cancer treatment. Concurrent use of hormones for non-cancer related conditions is acceptable (e.g., insulin for diabetes \& hormone replacement therapy). Local treatment of isolated lesions for palliative intent is acceptable;
• Receipt of any investigational anti-cancer therapy within 4 weeks prior to first dose of Toripalimab;
• Current use or prior use of immunosuppressive medication within 4 weeks prior to first dose of Toripalimab, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids not to exceed 10mg/day of prednisone or equivalent;
• Prior allogeneic bone marrow transplantation or prior solid organ transplantation;
• Major surgery within 4 weeks prior to first dose of Toripalimab or still recovering from prior surgery;
• Active or prior documented autoimmune disease within the past 2 years. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment within the past 2 years are not excluded;
• Known history of tuberculosis;
• Known to be human immunodeficiency virus (HIV) positive, hepatitis B, or hepatitis C positive;
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis);
• History of primary immunodeficiency;
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure according to NYHA Functional Classification ≥3, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events from Toripalimab, or compromise the ability of the subject to give written informed consent;
• Symptomatic or untreated central nervous system metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no evidence of new or enlarging metastases, and are off steroids;
• Receipt of live attenuated vaccination within 30 days prior to study entry or within 4 weeks of receiving Toripalimab;
• Pregnancy or breastfeeding women.

Sponsors & Collaborators

• TopAlliance Biosciences: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (14)

Sarcoma Oncology Research Center

Santa Monica, California, 90404, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

University of Miami Hospital Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34238, United States

Location

University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic-Rochester

Rochester, Minnesota, 55901, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44101, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02906, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Naing A, Mahipal A, Javle M, Wang J, Bauer TM, Bajor DL, Elias AD, Shields A, Davis E, Chawla S, Safran H, Powderly JD, D'Amato G, Meyer CF, Tang X, Yao S, Keegan P. Safety and Efficacy of Toripalimab in Patients with Cholangiocarcinoma: An Open-Label, Phase 1 Study. J Immunother Precis Oncol. 2025 Jan 15;8(1):71-81. doi: 10.36401/JIPO-24-8. eCollection 2025 Feb.

  PMID: 39816916 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Nasopharyngeal Carcinoma; Carcinoma, Hepatocellular; Sarcoma; Chondrosarcoma

Interventions

toripalimab; Medicare Part B

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Adenocarcinoma; Liver Neoplasms; Liver Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Medicare; Medical Assistance; Public Assistance; Financing, Government; Financing, Organized; Economics; Health Care Economics and Organizations; Insurance, Health; Insurance; Legislation as Topic; Social Control, Formal

Results Point of Contact

• Title: Dr. Kevin Li
• Organization: TopAlliance BioSciences

kevin_li@topalliancebio.com

301-640-5166

Study Officials

• Sheng Yao, PhD

  TopAlliance Biosciences, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: sequential dose escalation followed by activity estimation in disease specific cohorts at the RP2D.

Study Record Dates

• First Submitted: February 5, 2018
• First Posted: March 22, 2018
• Study Start: February 21, 2018
• Primary Completion: June 7, 2022
• Study Completion: July 7, 2022
• Last Updated: November 22, 2024
• Results First Posted: November 22, 2024

Record last verified: 2024-10

Locations

US (14)