CHS-114 + Toripalimab for Cancer

Recruiting at 22 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

154 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and early effectiveness of a new drug combination for individuals with advanced or spreading solid tumors. It involves different treatment groups using CHS-114 (an experimental treatment) and toripalimab (an immunotherapy drug), sometimes combined with other standard cancer treatments. The trial seeks participants with specific types of cancer, such as advanced gastric, esophageal, or colorectal cancer, who have not responded to other treatments. Those with these cancers that are unresponsive to typical treatments may be eligible to join the study. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research shows that the combination of CHS-114 and toripalimab is generally safe, meaning most people can take it without experiencing severe side effects. In earlier studies, participants did not report many serious issues while using these drugs together. Evidence also suggests that adding 5-fluorouracil (a chemotherapy drug) and cisplatin (another cancer treatment) is usually safe.

CHS-114 and toripalimab have shown promise in fighting cancer while being safe for most patients. This is encouraging, especially for those with advanced or hard-to-treat cancers. However, since this trial is in the early stages, researchers are still learning about all the possible safety concerns and side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CHS-114 combined with Toripalimab because it offers a fresh approach to fighting cancer. Unlike traditional chemotherapy that broadly attacks rapidly dividing cells, this combination leverages the power of immunotherapy. Toripalimab is an immune checkpoint inhibitor, specifically targeting the PD-1 pathway, which can help the immune system recognize and attack cancer cells more effectively. CHS-114 is a novel drug that, when paired with Toripalimab, might enhance this immune response further. This combo has the potential to offer a more targeted and potentially less toxic treatment option compared to standard chemotherapy regimens.

What evidence suggests that this trial's treatments could be effective for advanced or metastatic solid tumors?

Research has shown that CHS-114, when used alone, can significantly reduce certain immune-suppressing cells called Tregs by up to 97% and increase the number of CD8+ T cells, which are crucial for attacking cancer cells. Toripalimab helps the immune system better recognize and fight cancer by "removing the brakes" on immune responses. In this trial, participants will receive CHS-114 combined with toripalimab, and in some arms, with standard chemotherapy drugs like 5-fluorouracil and cisplatin. These combinations are expected to enhance each other's effectiveness, and early findings suggest they can improve cancer treatment outcomes. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Experimental: Cohort D - Arm D2 (Non-Liver Mets): CHS-114 + Toripalimab Experimental Treatment 2 Interventions

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

Group II: Experimental: Cohort D - Arm D1 (Liver Mets): CHS-114 + Toripalimab Experimental Treatment 2 Interventions

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

Group III: 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 IV: 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 V: 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 VI: 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 VII: 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+

Coherus Oncology, Inc.

Lead Sponsor

Published Research Related to This Trial

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 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]

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 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 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]

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]

Citations

1. investors.coherus.com investors.coherus.com/news-releases/news-release-details/coherus-presents-promising-early-clinical-data-phase-1-dose

Release Details CHS-114 monotherapy demonstrated Treg cell depletion (range of decrease: 52-97%), and significant increase in CD8+ T cells in the tumor, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06657144

NCT06657144 | A Study of CHS-114 in Combination With ... 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 ...

3. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT038/761489/Abstract-CT038-Phase-1-study-of-anti-CCR8-antibody

Phase 1 study of anti-CCR8 antibody CHS-114 with and ... Conclusions: CHS-114 with and without tori had an acceptable safety profile, depleted CCR8+ Tregs and increased CD8 T cells in the TME in pts, ...

4. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/coherus-presents-biomarker-data-for-anti-ccr8-antibody-chs-114/

Coherus Presents Biomarker Data for anti-CCR8 Antibody ... CHS-114, a cytolytic anti-CCR8 antibody, reduced intratumoral CCR8+ Tregs by 74% and total FOXP3+ Tregs by 43%, while increasing CD8+ T-cell ...

5. mskcc.org mskcc.org/cancer-care/clinical-trials/25-168

A Phase 1b Study of CHS-114 and Toripalimab in People ... CHS-114 finds and removes these CCR8-positive Tregs, allowing the immune system to recognize and destroy cancer cells. Toripalimab works by removing the brakes ...

6. investors.coherus.com investors.coherus.com/news-releases/news-release-details/coherus-oncology-presents-sitc-clinical-multiomic-biomarker-data

Release Details To date, CHS‑114, as monotherapy or in combination with toripalimab has a manageable safety profile, with promising early antitumor activity in ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT06657144

A Study of CHS-114 in Combination With Toripalimab and ... CHS-114 with toripalimab had promising antitumor activity in HNSCC that warrants continued exploration....A second-line HNSCC dose optimization study of CHS-114 ...