TAB004 + Toripalimab for Solid Cancers

Recruiting in Palo Alto (17 mi)

+20 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: TopAlliance Biosciences

Must not be taking: Immunosuppressants, Anticancer therapies

Disqualifiers: Autoimmune diseases, Active infections, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The primary objective is to assess the safety and tolerability of TAB004 as monotherapy and in combination with toripalimab in subjects with selected advanced solid malignancies, including lymphoma, and to evaluate the recommended Phase 2 dose. The secondary objectives are to: 1) describe the pharmacokinetic (PK) profile of TAB004 monotherapy and in combination with toripalimab and to describe the PK profile of toripalimab when administered with TAB004, 2) evaluate antitumor activity of TAB004 monotherapy and in combination with toripalimab; and 3) determine the immunogenicity of TAB004 monotherapy and in combination with toripalimab and to determine the immunogenicity of toripalimab when administered with TAB004. The exploratory objectives are to: 1) evaluate pharmacodynamic effects of TAB004 on its target receptor BTLA, as well as effects on the immune system; 2) evaluate biomarkers that may correlate with activity of TAB004 as monotherapy and in combination with toripalimab; 3) evaluate the utility of BTLA ligand, herpesvirus-entry mediator (HVEM), and additional exploratory biomarkers that could aid in selection of appropriate subjects for TAB004 monotherapy and in combination with toripalimab.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot be on any concurrent anti-cancer therapy, and you should not have used immunosuppressive medication within 2 weeks before starting the trial, except for certain low-dose corticosteroids.

What data supports the effectiveness of the drug toripalimab for treating solid cancers?

Research shows that toripalimab, when combined with other treatments, has shown promising results in treating various cancers, including non-small cell lung cancer and esophageal squamous cell carcinoma. These studies suggest that toripalimab can be effective in enhancing the body's immune response to fight cancer. ^{1 2 3 4 5}

Is the combination of TAB004 and Toripalimab safe for humans?

Toripalimab, a part of the treatment, has been studied in various trials and is generally considered safe, though it can have side effects like fatigue, rash, and changes in liver function. These studies have been conducted in patients with different types of cancer, and while the specific combination with TAB004 hasn't been detailed, the existing data on Toripalimab suggests it is generally safe for human use. ^{1 2 3 4 5}

What makes the drug TAB004 + Toripalimab unique for treating solid cancers?

TAB004 + Toripalimab is unique because it combines two components: TAB004, which targets a specific protein on cancer cells, and Toripalimab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination aims to enhance the body's immune response against solid tumors, offering a novel approach compared to traditional treatments. ^{6 7 8 9 10}

Research Team

Sheng Yao, PhD

Principal Investigator

TopAlliance Biosciences, Inc.

Eligibility Criteria

Adults over 18 with advanced solid tumors or lymphoma that worsened after treatment can join. They must have measurable disease, be in fairly good health (ECOG status of 0 or 1), and expect to live at least three more months. Participants need proper organ function, not be pregnant, use effective birth control, and agree to provide biopsy samples. Those who've had certain treatments or conditions recently can't participate.

Inclusion Criteria

My organs and bone marrow are working well.

My platelet count is at least 75,000 and I haven't needed a platelet transfusion in the last 5 days.

Subjects must use effective contraception

Exclusion Criteria

I have a history of tuberculosis.

I do not have any uncontrolled illnesses.

I have or had inflammatory bowel disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation (Part A and C)

Participants receive escalating doses of TAB004 alone or in combination with toripalimab to determine safety and tolerability

21 days per cycle, up to 2 years

Every 21 days

Cohort Expansion (Part B and D)

Participants receive the recommended dose of TAB004 alone or in combination with toripalimab to further evaluate safety and efficacy

21 days per cycle, up to 2 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TAB004 (Monoclonal Antibodies)
• Toripalimab (Monoclonal Antibodies)

Trial Overview The trial is testing TAB004 alone and with toripalimab for safety and the best dose against advanced cancers. It will also look at how the body processes these drugs, their effects on tumors, immune response they trigger, and explore biomarkers related to BTLA receptors involved in immune system regulation.

Participant Groups

Group I: TAB004 70mg and Torpalimab 240mg repeat dose every 21 days up to 2 years Experimental Treatment 2 Interventions

Group II: TAB004 500mg and Torpalimab 240mg repeat dose every 21 days up to 2 years Experimental Treatment 2 Interventions

Group III: TAB004 3 mg/kg repeat dose every 21 days up to 2 years Experimental Treatment 1 Intervention

Group IV: TAB004 20mg and Torpalimab 240mg repeat dose every 21 days up to 2 years Experimental Treatment 2 Interventions

Group V: TAB004 200mg repeat dose every 21 days up to 2 years Experimental Treatment 1 Intervention

Group VI: TAB004 200mg and Torpalimab 240mg repeat dose every 21 days up to 2 years Experimental Treatment 2 Interventions

Group VII: TAB004 10 mg/kg repeat dose every 21 days up to 2 years Experimental Treatment 1 Intervention

Group VIII: TAB004 1 mg/kg repeat dose every 21days up to 2 years Experimental Treatment 1 Intervention

Group IX: TAB004 0.3 mg/kg repeat dose every 21 days up to 2 years Experimental Treatment 1 Intervention

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Maryland Medical Center Baltimore, MD

University of Texas Southwestern Medical Center Harold C. Simmons Comprehensive Cancer Center Dallas, TX

Northwell Health New Hyde Park, NY

Washington University Saint Louis, MO

More Trial Locations

Who Is Running the Clinical Trial?

TopAlliance Biosciences

Lead Sponsor

Trials

2

Patients Recruited

680+

Shanghai Junshi Bioscience Co., Ltd.

Collaborator

Trials

121

Patients Recruited

28,800+

TopAlliance Biosciences, Inc.

Collaborator

Trials

3

Patients Recruited

680+

CTI Clinical Trial and Consulting Services

Collaborator

Trials

36

Patients Recruited

3,700+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical efficacy of toripalimab, a PD-1 mAb, in patients with advanced or recurrent malignancies in a phase I study. Yang, J., Dong, L., Yang, S., et al.[2020]

In a phase 2 trial involving 42 patients with unresectable locally advanced oesophageal squamous cell carcinoma, the combination of toripalimab with chemoradiotherapy resulted in a 62% complete response rate after 3 months, indicating promising efficacy for this treatment approach.

The treatment was generally well-tolerated, with a 1-year overall survival rate of 78.4% and a median duration of response of 12.1 months, although lymphopenia was a common adverse effect, affecting 86% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Zhu, Y., Wen, J., Li, Q., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II clinical trial of toripalimab combined with neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma (NEOCRTEC1901). Chen, R., Liu, Q., Li, Q., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes and immunological evaluation of toripalimab combination for cancer treatment: A systematic review and meta-analysis of randomized controlled trials. Li, J., Zhang, H., Zhu, H., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant toripalimab plus platinum-paclitaxel chemotherapy in stage II-III non-small cell lung cancer: a single-center, single-arm, phase I study in China. Hou, H., Wang, Y., Sun, D., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Vonderheide, RH., LoRusso, PM., Khalil, M., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of tremelimumab in patients with metastatic melanoma. Camacho, LH., Antonia, S., Sosman, J., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer. Chung, KY., Gore, I., Fong, L., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood mRNA expression profiling predicts survival in patients treated with tremelimumab. Saenger, Y., Magidson, J., Liaw, B., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab. [2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and clinical efficacy of toripalimab, a PD-1 mAb, in patients with advanced or recurrent malignancies in a phase I study. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

A phase II clinical trial of toripalimab combined with neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma (NEOCRTEC1901). [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical outcomes and immunological evaluation of toripalimab combination for cancer treatment: A systematic review and meta-analysis of randomized controlled trials. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant toripalimab plus platinum-paclitaxel chemotherapy in stage II-III non-small cell lung cancer: a single-center, single-arm, phase I study in China. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Phase I/II trial of tremelimumab in patients with metastatic melanoma. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Blood mRNA expression profiling predicts survival in patients treated with tremelimumab. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Tremelimumab. [2023]