TAB004 + Toripalimab for Solid Cancers

Recruiting at 21 trial locations

Overseen By Richard Curry, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TopAlliance Biosciences

Must not be taking: Immunosuppressants, Anticancer therapies

Disqualifiers: Autoimmune diseases, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 42

499 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of a new treatment combination for advanced solid cancers, including lymphoma. Researchers are examining how the drug TAB004 (also known as tifcemalimab or JS004) works alone and in combination with toripalimab, a cancer-fighting medication. The trial aims to determine the best dose for future studies and evaluate the effectiveness of these treatments against tumors. Individuals with advanced solid tumors, such as lymphoma or melanoma, who have undergone prior treatments but still experience progression, may be eligible to participate. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In previous studies, TAB004 has proven safe when used alone or with toripalimab. Research indicates that patients tolerated the treatments well, with few serious side effects. One study specifically noted that this combination was safe and showed promising results in fighting tumors for certain cancers.

For toripalimab, more information is available since the FDA has already approved it for another condition. This approval confirms its thorough safety evaluation in various situations. Reports have shown that while some patients may experience side effects like tiredness or skin reactions, these are generally manageable.

Overall, existing data suggests that both TAB004 and toripalimab are safe for use in people, though monitoring for any side effects remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TAB004 and Toripalimab because they represent a novel approach to treating solid cancers. Unlike traditional chemotherapy, which targets rapidly dividing cells non-selectively, TAB004 is an antibody designed to specifically target and inhibit the growth of cancer cells. Toripalimab, on the other hand, is an immunotherapy that blocks a protein called PD-1, helping the immune system recognize and attack cancer cells more effectively. This combination not only offers the potential for increased specificity in targeting cancer cells but also leverages the body's own immune system to fight the disease, potentially leading to fewer side effects and improved outcomes compared to standard treatments.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that toripalimab, one of the treatments in this trial, yields promising results in treating various cancers, such as non-small cell lung cancer, when combined with other therapies. For instance, combining toripalimab with chemotherapy extends the time patients live without cancer progression and increases overall survival compared to chemotherapy alone. This makes toripalimab a strong option for cancer treatment. Tifcemalimab, also known as TAB004, is another treatment under study in this trial. It has demonstrated early effectiveness when used with toripalimab, particularly in patients who did not respond to other immune-based treatments. These findings suggest that both treatments could work well together to combat certain advanced cancers. ^{2 6 7 8 9}

Who Is on the Research Team?

Sheng Yao, PhD

Principal Investigator

TopAlliance Biosciences, Inc.

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• TAB004
• Toripalimab

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

TopAlliance Biosciences

Lead Sponsor

Trials

2

Recruited

680+

Shanghai Junshi Bioscience Co., Ltd.

Collaborator

Trials

121

Recruited

28,800+

TopAlliance Biosciences, Inc.

Collaborator

Trials

3

Recruited

680+

CTI Clinical Trial and Consulting Services

Collaborator

Trials

36

Recruited

3,700+

Published Research Related to This Trial

A four-gene model (CTSD, PLA2G7, TXNRD1, IRAK3) was identified as a strong predictor of survival in melanoma patients treated with the monoclonal antibody tremelimumab, based on a study of 218 patients.

This gene expression model was validated in a separate group of 260 treatment-naïve melanoma patients, demonstrating its potential to enhance the predictive value of existing clinical indicators for patient outcomes in immunotherapy.

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]

Toripalimab, a monoclonal antibody targeting the PD-1 receptor, was well tolerated in a phase I study with 33 heavily pretreated patients, showing no dose-limiting toxicity up to 10 mg/kg every two weeks.

The treatment demonstrated promising efficacy, with an objective response rate of 22.7% in solid tumors and a remarkable 90.9% in lymphoma patients, along with a median duration of response of 21.5 months.

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]

In a phase II trial involving 44 patients with locally advanced esophageal squamous cell carcinoma, 50% achieved a pathological complete response (pCR) after treatment with toripalimab combined with neoadjuvant chemoradiotherapy, indicating a promising efficacy.

The treatment was generally safe, with a high R0 resection rate of 98%, although 20% of patients experienced severe adverse events, suggesting that while the regimen is effective, careful monitoring for complications is necessary.

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]

In a phase II trial involving 47 patients with treatment-refractory colorectal cancer, tremelimumab showed limited efficacy as a single agent, with only one patient (2%) achieving a partial response and 21 patients (45%) surviving for at least 180 days after treatment.

The treatment was associated with some grade 3/4 adverse events, including diarrhea and ulcerative colitis, but these were generally manageable, suggesting that while tremelimumab may not be effective alone, it could be safe for further exploration in combination therapies.

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]

In a phase I/II trial involving 28 patients with metastatic melanoma, tremelimumab was well-tolerated with no dose-limiting toxicities observed, and it demonstrated antitumor activity with 10% of patients achieving objective responses.

The 15 mg/kg dosing regimen every 3 months showed a more favorable safety profile compared to the 10 mg/kg monthly regimen, leading to its selection for further clinical testing due to lower rates of serious adverse events.

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]

Tremelimumab is a fully human IgG2 antibody targeting CTLA4, currently in phase III trials for malignant melanoma and phase II trials for several other cancers, indicating its broad potential in cancer treatment.

The drug is being investigated for multiple cancer types, including colorectal, gastrointestinal, gynecological, non-small cell lung, prostate, breast, and pancreatic cancers, showcasing its versatility in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab. [2023]

Toripalimab combined with chemotherapy or targeted therapy significantly improved clinical outcomes in cancer patients, showing better complete response rates, overall survival, and progression-free survival compared to monotherapy, based on a meta-analysis of 11 randomized controlled trials involving 1856 patients.

While toripalimab combination therapy enhanced immune function by increasing T cell populations, it also resulted in a higher incidence of immune-related adverse effects, indicating a trade-off between efficacy and manageable toxicity.

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]

In a phase 1 study involving 26 patients with advanced hormone-responsive breast cancer, tremelimumab combined with exemestane was found to be tolerable, with the maximum tolerated dose established at 6 mg/kg every 90 days.

The treatment led to immune activation, indicated by an increase in ICOS+ T cells, and resulted in stable disease for at least 12 weeks in 42% of patients, suggesting potential efficacy in this patient population.

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]

In a phase I study involving 11 treatment-naive patients with resectable non-small cell lung cancer (NSCLC), the combination of neoadjuvant toripalimab and chemotherapy was found to be tolerable, with 45% of patients experiencing treatment-related adverse events.

The treatment resulted in a high efficacy, with a 91% objective response rate and a 55% rate of pathological complete response, indicating significant potential for this combination therapy in NSCLC.

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12018478/

Perioperative the BTLA inhibitor (tifcemalimab) combined ... However, preliminary results show that the tumor response rate of PD-1 or CTLA-4 blocking antibodies was no more than 20-30%, and about 30-40% ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05664971

NCT05664971 | JS004 Combined With Toripalimab and ... This is an open-label phase Ib/II clinical study to evaluate the safety, tolerability, pharmacokinetics and initial efficacy of JS004 injection combined ...

3. withpower.com withpower.com/trial/phase-1-neoplasms-9-2019-0d283

TAB004 + Toripalimab for Solid Cancers Research shows that toripalimab, when combined with other treatments, has shown promising results in treating various cancers, including non-small cell lung ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2596

Phase I dose-escalation and cohort expansion study of the ... Tifcemalimab in combination with toripalimab showed preliminary efficacy in immunotherapy-refractory pts with a manageable safety profile.

5. nature.com nature.com/articles/s41467-025-59461-3

Tifcemalimab as monotherapy or in combination with ... We present the outcomes of tifcemalimab with or without toripalimab in lymphoma patients. This is a 2-part, phase I study (NCT04477772).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04137900

Study Details | NCT04137900 | Safety, Tolerability and ... Doses of TAB004 and toripalimab will be determined based upon safety and efficacy data from Part C. Tumor response will be evaluated using the Response ...

7. georgiacancerinfo.org georgiacancerinfo.org/clinical-trials/detail/4883

Safety, Tolerability and Pharmacokinetics of a Monoclonal ... Summary. The primary objective is to assess the safety and tolerability of TAB004 as monotherapy and in combination with toripalimab in subjects with selected ...

8. aacrjournals.org aacrjournals.org/clincancerres/article/31/14/2926/763505/Phase-I-II-Study-of-Tifcemalimab-an-Anti-B-and-T

Phase I/II Study of Tifcemalimab, an Anti–B- and T-lymphocyte ... This phase I/II trial investigated the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of tifcemalimab plus toripalimab in advanced ...

9. sigma.larvol.com sigma.larvol.com/product.php?e1=585756&tab=ott&sourcepg=TZP

tifcemalimab (TAB004) Trials Trial + Data / Events, Status ... NCT04773951: A Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of JS004 in Advanced Solid Tumors ...