SRF114 for Solid Tumors

Recruiting at 16 trial locations

Overseen By Clinical Operations Team

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Coherus Oncology, Inc.

Must not be taking: Anti-CCR8, Anticoagulants

Disqualifiers: Uncontrolled diabetes, Nasopharyngeal carcinoma, others

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

Compensation: Varies

Number of Visits: Unknown

87 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, SRF114 (also known as CHS-114), to evaluate its safety and effectiveness for individuals with advanced solid tumors. It examines how this treatment works alone and in combination with another drug, toripalimab, for specific head and neck cancers. Suitable candidates for this trial have advanced solid tumors unresponsive to standard treatments or head and neck cancer that cannot be treated with surgery or radiation. 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 it.

Do I need to stop taking my current medications to join the trial?

The trial requires a washout period from your last dose of previous anticancer therapy, which must be more than 5 times the half-life of the agent or more than 21 days, whichever is shorter. The protocol does not specify about other medications, so you should discuss with the trial team.

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

Research has shown that SRF114 has been tested alone in patients with advanced solid tumors. These studies indicate that SRF114 is generally safe, even for patients who have undergone multiple treatments. Tested in doses up to 700 mg, the results were promising, with no major safety concerns at these levels.

When combined with toripalimab, studies have also examined safety in people with solid tumors. Toripalimab is a drug that helps the immune system fight cancer. Early studies have administered this combination to patients, and the safety data collected so far suggest it is generally well-tolerated.

Since these studies are in the early stages, they primarily focus on understanding safety and determining the best dose. The information gathered so far is encouraging, but more research is needed to fully understand the safety of these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for solid tumors, which typically include chemotherapy, radiation, and surgery, SRF114 offers a different approach by acting on specific molecular targets. Researchers are excited about SRF114 because it targets unique pathways associated with tumor growth, potentially offering more precise treatment with fewer side effects. Additionally, when combined with toripalimab, an immune checkpoint inhibitor, SRF114 might enhance the body's immune response against the cancer, offering a promising new strategy for tackling tumors that are resistant to conventional therapies.

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

Research has shown that CHS-114, one of the treatments in this trial, has promising early results when used alone for advanced solid tumors. Some patients have reported tumor shrinkage, suggesting potential effectiveness. CHS-114 targets a protein called CCR8, which plays a role in tumor growth, and may help slow or stop tumor progression.

In this trial, some participants will receive CHS-114 combined with toripalimab, a treatment that aids the immune system in fighting cancer. Early studies have demonstrated additional benefits with this combination, as some patients experienced further tumor shrinkage. These findings suggest that CHS-114, both alone and with toripalimab, could effectively treat solid tumors. ^{1 2 4 6 7}

Who Is on the Research Team?

Koho Izuka, MD

Principal Investigator

Coherus BioSciences

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, including head and neck squamous cell carcinoma, who have measurable lesions and whose major organs are functioning well. They must not have had more than four prior systemic treatments for advanced disease, no recent major surgery, and cannot be on certain blood thinners if providing biopsies.

Inclusion Criteria

I am fully active or can carry out light work.

My advanced cancer has worsened despite treatment, and no other treatments are suitable for me.

Serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula

Exclusion Criteria

I have previously been treated with anti-CCR8 therapy.

I have had a severe allergic reaction to monoclonal antibody therapy or its ingredients.

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

CHS-114 monotherapy dose-escalation portion to determine the recommended dose for expansion

21 days

Multiple visits for dose escalation and monitoring

Dose Expansion

Evaluation of safety, efficacy, tolerability, pharmacokinetics, and pharmacodynamics of CHS-114 in specific cohorts

Up to 24 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SRF114

Trial Overview SRF114 is being tested in this study. It's a new monoclonal antibody targeting CCR8 given as monotherapy to see how safe it is and how well it works against different types of solid tumors in adults.

How Is the Trial Designed?

Group I: Arm 3: CHS-114 + toripalimab Dose Expansion Experimental Treatment 2 Interventions

Arm 3 dose expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 in combination with toripalimab at 2 RDE levels in up to 20 participants in each dose level with HNSCC.

Group II: Arm 2: CHS-114 + toripalimab Dose Escalation Experimental Treatment 2 Interventions

Arm 2 dose escalation will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 in combination with toripalimab at 2 RDE levels in up to 6 participants in each dose level with HNSCC.

Group III: Arm 1b: CHS-114 Dose Expansion Experimental Treatment 1 Intervention

Arm 1b monotherapy expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 monotherapy at 2 dose levels (potential recommended dose for expansion RDE in up to 5 participants in each dose level with Head and Neck Squamous Cell Carcinoma (HNSCC).

Group IV: Arm 1a: CHS-114 Dose Escalation Experimental Treatment 1 Intervention

Arm 1 monotherapy dose escalation portion of the study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of CHS-114 as monotherapy in up to 25 participants with advanced solid tumors, to determine the recommended dose for expansion (RDE).

Who Is Running the Clinical Trial?

Coherus Oncology, Inc.

Lead Sponsor

Coherus Biosciences, Inc.

Lead Sponsor

Trials

19

Recruited

3,700+

Surface Oncology

Lead Sponsor

Trials

6

Recruited

730+

Published Research Related to This Trial

The phase I study established a maximum tolerated dose (MTD) of 1000 mg for LY3164530 on Schedule 1 and 500 mg on Schedule 2, with treatment-related adverse events primarily linked to epidermal growth factor receptor (EGFR) inhibition, including skin rashes and electrolyte imbalances.

Despite significant toxicities, the study showed a partial response in 10.3% of patients and a disease control rate of 51.7%, indicating some anti-tumor activity, particularly with Schedule 2, which provided more consistent inhibition of the MET/EGFR pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of LY3164530, a bispecific antibody targeting MET and EGFR, in patients with advanced or metastatic cancer. Patnaik, A., Gordon, M., Tsai, F., et al.[2019]

In a study involving 32 healthy volunteers, S-3304 was generally well tolerated at doses up to 2400 mg taken twice daily for 28 days, indicating its safety at these levels.

However, at the highest dose of 3200 mg twice daily, there were significant elevations in alanine aminotransferase (ALT) levels, leading to the withdrawal of five participants, highlighting ALT elevation as a key safety concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety assessments of high-dose and 4-week treatment with S-3304, a novel matrix metalloproteinase inhibitor, in healthy volunteers. Mant, TG., Bradford, D., Amin, DM., et al.[2018]

Serine/arginine-rich splicing factors (SRs) are crucial in the RNA splicing process, and their abnormal expression in tumors can lead to changes in RNA splicing that promote tumor cell growth, migration, and resistance to cell death.

Analyzing mRNA alternative splicing events related to SRs presents a promising avenue for identifying new targets for cancer therapy, although there are challenges that need to be addressed in this research area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serine/arginine-rich splicing factors: the bridge linking alternative splicing and cancer. Zheng, X., Peng, Q., Wang, L., et al.[2023]

SRSF3, a small member of the Ser/Arg-rich protein family, plays a crucial role in regulating gene expression and its overexpression is linked to various human cancers, highlighting its potential as an oncogene.

Research suggests that targeting and downregulating SRSF3 could be a promising strategy for developing new anticancer therapies, as it may help to reverse the negative effects of its overexpression in cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Roles of SRSF3 as a Therapeutic Target for Cancer. Zhou, Z., Gong, Q., Lin, Z., et al.[2020]

In a study of 23 patients with advanced gastric cancer, the combination therapy of irinotecan (CPT-11) and S-1 resulted in a promising overall response rate of 47.8% and a median time to progression of 210 days.

The treatment was associated with low rates of severe toxicity, with only 17.4% experiencing grade 3 or 4 hematological issues and 8.7% facing non-hematological toxicity, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of a combination of irinotecan and S-1 in patients with advanced gastric cancer (OGSG0002). Uedo, N., Narahara, H., Ishihara, R., et al.[2018]

The maximum-tolerated dose (MTD) for oral irinotecan (CPT-11) was determined to be 66 mg/m2/day for patients under 65 and 50 mg/m2/day for those 65 and older, with grade 4 delayed diarrhea identified as a dose-limiting toxicity.

Oral administration of CPT-11 showed promising pharmacokinetic properties, with effective conversion to its active form, SN-38, and demonstrated antitumor activity in one patient with colorectal cancer, suggesting potential for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of oral irinotecan administered daily for 5 days every 3 weeks in patients with solid tumors. Drengler, RL., Kuhn, JG., Schaaf, LJ., et al.[2018]

In a Phase I study involving 99 patients with advanced solid tumors, irofulven was found to have a maximum tolerated dose with significant dose-limiting toxicities, particularly thrombocytopenia and unexpected visual toxicity, which was mostly reversible and linked to higher doses.

The study recommended specific dosing schedules for irofulven, suggesting 18 mg/m² for a 30-minute infusion every 3 weeks and 24 mg/m² for a 30-minute infusion every 4 weeks, based on the observed safety and pharmacokinetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic study of irofulven administered weekly or biweekly in advanced solid tumor patients. Alexandre, J., Raymond, E., Kaci, MO., et al.[2014]

In a phase I trial involving 23 patients with metastatic or recurrent colorectal cancer, the recommended doses for S-1 and irinotecan (CPT-11) were established at 80 mg/m² and 225 mg/m², respectively, with manageable dose-limiting toxicities including grade 3 ileus and diarrhea.

The combination treatment showed promising efficacy, with an objective response rate of 41% in patients with measurable disease, indicating that further phase II trials are justified to explore this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of combination therapy with S-1 and irinotecan in patients with previously untreated metastatic or recurrent colorectal cancer. Choi, YH., Kim, TW., Lee, SS., et al.[2018]

In a dose-escalation study involving 81 patients with advanced solid tumors, the oral Src inhibitor saracatinib was found to be well tolerated, with a maximum tolerated dose established at 175 mg per day.

Treatment with saracatinib resulted in a significant reduction in tumor Src activity, indicating its potential efficacy in targeting this pathway in cancer, and it showed suitable pharmacokinetics for once-daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I safety, pharmacokinetics, and inhibition of SRC activity study of saracatinib in patients with solid tumors. Baselga, J., Cervantes, A., Martinelli, E., et al.[2021]

A comprehensive analysis of over 10,000 tumor samples from 33 cancer types revealed that serine/arginine-rich splicing factors (SRSFs) are frequently altered and play a significant role in cancer development and immunity.

SRSFs not only predict responses to immunotherapy and survival rates across various cancers but also indicate sensitivity to targeted therapies and chemotherapy, suggesting their potential as biomarkers for personalized cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular characteristics and clinical implications of serine/arginine-rich splicing factors in human cancer. Zhang, J., Fang, Z., Song, C.[2023]

Saracatinib, a selective Src inhibitor, was found to be tolerable in Japanese patients with advanced solid tumors, with the maximum tolerated dose identified as 125 mg, while the most common side effects included diarrhea and nausea.

The study showed that the best response to saracatinib was stable disease in some patients, indicating potential efficacy, although the overall results suggest further investigation is needed to fully assess its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First report of the safety, tolerability, and pharmacokinetics of the Src kinase inhibitor saracatinib (AZD0530) in Japanese patients with advanced solid tumours. Fujisaka, Y., Onozawa, Y., Kurata, T., et al.[2022]

In a phase II study involving 45 patients with advanced colorectal cancer, the combination of oral S-1 and weekly irinotecan showed an overall response rate of 48.9%, indicating significant efficacy as a first-line treatment.

The treatment was well-tolerated, with manageable grade 3 or 4 toxicities, including neutropenia (8.9%) and diarrhea (6.7%), suggesting it may be a safer alternative compared to conventional chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Phase II Study of a New Effective S-1 and Irinotecan Combination Schedule in Patients with Unresectable Metastatic or Recurrent Colorectal Cancer. Ogata, Y., Tanaka, T., Akagi, Y., et al.[2021]

The combination of the Chk1 inhibitor SRA737 with low-dose gemcitabine was found to be well tolerated in patients with advanced solid tumors, with common side effects being mild to moderate and leading to few treatment discontinuations.

The treatment showed an objective response rate of 10.8% overall, with a notable 25% response rate in patients with anogenital cancer, indicating potential efficacy in specific tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer. Jones, R., Plummer, R., Moreno, V., et al.[2023]

SAR125844, a selective c-Met kinase inhibitor, was found to have acceptable tolerability in a phase I trial with 38 Asian patients, including those with gastric cancer and MET amplification, with the maximum tolerated dose established at 570 mg/m2.

While no objective responses were observed in the initial dose-escalation cohort, modest antitumor activity was noted in the dose-expansion cohort, particularly in patients with MET-amplified gastric cancer, where two patients achieved partial responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer. Shitara, K., Kim, TM., Yokota, T., et al.[2023]

The study evaluated the safety and pharmacokinetics of SR271425 in 38 patients, identifying dose-limiting toxicities (DLTs) primarily related to cardiac issues, specifically QTc prolongation, at doses up to 1,320 mg/m².

Despite observing some grade 1 and 2 toxicities, no confirmed tumor responses were noted, leading to the decision to discontinue further development of SR271425 due to the associated cardiac risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of the thioxanthone SR271425 administered intravenously once every 3 weeks in patients with advanced malignancies. Goncalves, PH., High, F., Juniewicz, P., et al.[2021]

Citations

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

Release Details This open-label Phase 1b clinical trial evaluated CHS-114 as a single-agent and in combination with toripalimab in 21 patients with advanced solid tumors ...

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

Abstract CT038: Phase 1 study of anti-CCR8 antibody CHS ... Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors [abstract].

4. cancer.gov cancer.gov/clinicaltrials/NCI-2025-04098

A Study of CHS-114 in Combination With Toripalimab and/ ... 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 ...

5. clinicaltrial.be clinicaltrial.be/en/details/178379?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Study of CHS-114 in Participants With Advanced Solid ... Arm 3 dose expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 in combination with toripalimab at 2 ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT05635643

Study of CHS-114 in Participants With Advanced Solid ... "Coherus plans to: Report Phase 1 monotherapy biopsy data as well as CHS-114/toripalimab combination safety data in head and neck squamous cell carcinoma (HNSCC) ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06657144?spons=COVERAGE%5BFullMatch%5DEXPANSION%5BNone%5D(%22Coherus%20Biosciences,%20Inc.%22)&viewType=Table&rank=5

A Study of CHS-114 in Combination With Toripalimab and/ ... 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 ...