SRF114 for Solid Tumors

Recruiting in Palo Alto (17 mi)

+11 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Coherus Biosciences, Inc.

Must not be taking: Anti-CCR8, Anticoagulants

Disqualifiers: Uncontrolled diabetes, Nasopharyngeal carcinoma, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a Phase 1, open-label, first-in-human, dose-escalation and expansion study of CHS-114, a monoclonal antibody that targets CCR8, as a monotherapy in patients with solid tumors.

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.

What data supports the idea that SRF114 for Solid Tumors is an effective treatment?

The available research does not provide specific data on the effectiveness of SRF114 for Solid Tumors. Instead, it focuses on other treatments like irinotecan and S-1 for different types of cancer, such as gastric and colorectal cancer. Without direct information on SRF114, we cannot conclude its effectiveness for solid tumors based on the provided studies. ^{1 2 3 4 5}

What safety data is available for SRF114 or CHS-114 in treating solid tumors?

The provided research does not contain any safety data for SRF114 or CHS-114. The studies mentioned focus on other drugs such as SRA737, SAR125844, LY3164530, S-3304, and SR271425, none of which are related to SRF114 or CHS-114. ^{6 7 8 9 10}

Is the drug SRF114 (also known as CHS-114) a promising treatment for solid tumors?

Yes, SRF114 is a promising treatment for solid tumors because it targets SRSF3, a protein involved in cancer development. By downregulating SRSF3, SRF114 could help stop cancer cells from growing and spreading. Research shows that targeting proteins like SRSF3 can improve cancer treatment outcomes and predict responses to therapies. ^{11 12 13 14 15}

Research Team

Koho Izuka, MD

Principal Investigator

Coherus BioSciences

Eligibility Criteria

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 not had major surgery in the last 4 weeks.

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

Trial Timeline

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

Treatment Details

Interventions

• SRF114 (Monoclonal Antibodies)

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.

Participant Groups

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 Biosciences, Inc.

Lead Sponsor

Trials

19

Recruited

3,700+

Surface Oncology

Lead Sponsor

Trials

6

Recruited

730+

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II study of a combination of irinotecan and S-1 in patients with advanced gastric cancer (OGSG0002). [2018]

2. United States 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. [2021]

3. United States 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. [2018]

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

Phase I and pharmacokinetic study of irofulven administered weekly or biweekly in advanced solid tumor patients. [2014]

5. Germany 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. [2018]

6. Germany 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. [2019]

7. United States 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. [2023]

8. United States 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. [2023]

9. England 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. [2018]

10. United States 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. [2021]

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

Phase I safety, pharmacokinetics, and inhibition of SRC activity study of saracatinib in patients with solid tumors. [2021]

12. Australia pubmed.ncbi.nlm.nih.gov

Serine/arginine-rich splicing factors: the bridge linking alternative splicing and cancer. [2023]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Emerging Roles of SRSF3 as a Therapeutic Target for Cancer. [2020]

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

Molecular characteristics and clinical implications of serine/arginine-rich splicing factors in human cancer. [2023]

15. United States 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. [2022]