CHS-114 + Toripalimab for Cancer

Recruiting at 3 trial locations

Overseen By Clinical Operations Team

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Coherus Biosciences, Inc.

Must not be taking: Corticosteroids, CCR8 antibodies

Disqualifiers: Prior malignancy, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 2.25 years

72 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug combination CHS-114 and Toripalimab for cancer?

Research shows that Toripalimab, when combined with other treatments, has improved survival rates in patients with advanced esophageal cancer, suggesting it may be effective in combination therapies for other cancers as well. ^{1 2 3 4 5}

Is toripalimab safe for use in humans?

Toripalimab has been studied in several trials for different types of cancer, and these studies have looked at its safety in humans. In general, it has been used safely in combination with other treatments like chemotherapy and radiotherapy for conditions such as esophageal and lung cancer. ^{2 3 4 5 6}

How is the drug CHS-114 + Toripalimab unique for cancer treatment?

The combination of CHS-114 and Toripalimab is unique because Toripalimab is an immune checkpoint inhibitor that targets PD-1, helping the immune system attack cancer cells more effectively. This combination may offer a novel approach compared to standard treatments, especially for cancers where immune checkpoint inhibitors have shown promise. ^{1 2 3 4 7}

What is the purpose of this trial?

The main purpose of this study is to evaluate the safety and preliminary efficacy of CHS-114 in combination with toripalimab and/or other standard of care (SOC) compound(s) in participants with advanced or metastatic solid tumors.

Eligibility Criteria

This trial is for adults with advanced solid tumors, including uterine and metastatic tumors, who have already tried a platinum and fluoropyrimidine treatment without success. Participants must have at least one measurable tumor and should be mostly recovered from previous treatments' side effects. They cannot join if they've had certain types of gastric cancer or if their cancer is not stable genetically.

Inclusion Criteria

I have at least one tumor that can be measured.

I meet the specific requirements for Cohort A.

My cancer is advanced stomach or GEJ cancer, not HER2 positive, and is microsatellite stable.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CHS-114 in combination with toripalimab every 3 weeks

Up to approximately 2.25 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• CHS-114
• Toripalimab

Trial Overview The study tests CHS-114 in combination with Toripalimab, an immune therapy drug, along with other standard treatments. It aims to find out how safe this combo is and how well it works against different advanced solid tumors.

Participant Groups

Group I: Cohort C - Arm C: CHS-114 Dose B + Toripalimab + 5 fluorouracil (5 FU) + Cisplatin Experimental Treatment 4 Interventions

Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab, 5 FU, and cisplatin Q3W.

Group II: Cohort B - Arm B2: CHS-114 Dose B + Toripalimab Experimental Treatment 2 Interventions

Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.

Group III: Cohort B - Arm B1: CHS-114 Dose A + Toripalimab Experimental Treatment 2 Interventions

Participants will be treated with dose A of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.

Group IV: Cohort A - Arm A2: CHS-114 Dose B + Toripalimab Experimental Treatment 2 Interventions

Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.

Group V: Cohort A - Arm A1: CHS-114 Dose A + Toripalimab Experimental Treatment 2 Interventions

Participants will be treated with dose A of CHS-114 administered as an intravenous (IV) infusion in combination with toripalimab every 3 weeks (Q3W).

Who Is Running the Clinical Trial?

Coherus Biosciences, Inc.

Lead Sponsor

Trials

19

Recruited

3,700+

Findings from Research

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]

Toripalimab, an immune checkpoint inhibitor, significantly improves progression-free survival and overall survival in advanced esophageal squamous cell carcinoma when combined with chemotherapy, as shown in the JUPITER-06 trial.

However, from a cost-effectiveness perspective in China, adding toripalimab to chemotherapy is not considered cost-effective unless its price is reduced by over 40%, as the incremental cost-effectiveness ratio exceeds the country's willingness-to-pay threshold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma. Xu, K., Wu, H., Zhou, C., 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]

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 trial involving 50 patients with stage II-III non-small-cell lung cancer (NSCLC), neoadjuvant treatment with toripalimab and chemotherapy demonstrated a high objective response rate of 76%, with 100% of patients with resectable disease able to undergo surgery and 55.6% achieving major pathological response (MPR).

The treatment was found to be safe, with manageable adverse events; importantly, baseline expression of CHI3L1 in tumor samples was identified as a potential predictor of therapeutic response and overall survival, highlighting the role of transcriptomic characteristics in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in stage II-III NSCLC (LungMate 002): an open-label, single-arm, phase 2 trial. Zhu, X., Sun, L., Song, N., et al.[2023]

In a phase II trial involving 25 patients with recurrent nasopharyngeal carcinoma, toripalimab combined with intensity-modulated radiotherapy (IMRT) resulted in a high overall response rate of 79.2% and disease control in 95.8% of patients at 3 months post-treatment.

The treatment was found to be tolerable, with low incidences of severe acute side effects, although some patients experienced late severe complications such as nasopharyngeal wall necrosis (28.0%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial. Hua, Y., You, R., Wang, Z., et al.[2022]

References

1. 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]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma. [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. 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]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in stage II-III NSCLC (LungMate 002): an open-label, single-arm, phase 2 trial. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial. [2022]