SRF388 + Pembrolizumab for Cancer

Recruiting in Palo Alto (17 mi)

+22 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Coherus Biosciences, Inc.

Must be taking: VEGF-targeted agents

Must not be taking: Anti-IL-27 therapy

Disqualifiers: Uncontrolled diabetes, unstable cardiac, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests CHS-388, a protein that blocks IL-27, in patients with severe cancers like kidney, liver, and lung cancer. The goal is to see if it helps the immune system fight cancer better.

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 your specific situation with the study team or your doctor.

What data supports the effectiveness of the drug SRF388 + Pembrolizumab for cancer?

Research shows that pembrolizumab, a part of this drug combination, has been effective in treating various cancers, including colorectal cancer, renal cell carcinoma, non-small cell lung cancer, and cutaneous squamous cell carcinoma, by improving survival rates and providing durable antitumor activity. ^{1 2 3 4 5}

Is the combination of SRF388 and Pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been studied in various cancers like melanoma, lung, ovarian, and kidney cancer, showing a safety profile that is generally acceptable, though some patients may experience side effects. Common side effects can include fatigue, skin reactions, and changes in liver function, but these vary by individual. ^{2 4 6 7 8}

What makes the drug SRF388 + Pembrolizumab unique for cancer treatment?

SRF388 combined with Pembrolizumab is unique because it pairs a novel agent, SRF388, with Pembrolizumab, an established immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination aims to enhance the immune response against cancer, potentially offering a new option for patients who may not respond to existing treatments. ^{5 9 10 11 12}

Research Team

Koho Iizuka, MD

Principal Investigator

Coherus BioSciences

Eligibility Criteria

Adults with advanced solid tumors, including specific types of lung, liver, and kidney cancer. Participants must have progressed after standard therapy and meet certain health criteria like stable organ function and blood counts. They should not have had major surgery recently or severe allergies to monoclonal antibodies.

Inclusion Criteria

My lung cancer is at an advanced stage and has been confirmed by tests.

My liver cancer is moderately severe, but my liver is still functioning well.

You must have at least one tumor that can be measured using specific guidelines.

Exclusion Criteria

I've had more than 4 treatments for my cancer that can't be removed by surgery, but I didn't stop PD-(L)1 inhibitors due to severe side effects.

I have been treated with anti-IL-27 therapy before.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

CHS-388 monotherapy dose-escalation portion to evaluate safety, tolerability, PK, pharmacodynamics, and preliminary efficacy

Up to 24 months

Monotherapy Expansion

CHS-388 monotherapy expansion to evaluate safety, efficacy, tolerability, PK, and pharmacodynamics in specific cohorts

Up to 24 months

Combination Therapy with Pembrolizumab

Evaluation of safety, preliminary efficacy, tolerability, and PK of CHS-388 in combination with pembrolizumab

Up to 24 months

Combination Therapy with Toripalimab

Evaluation of safety, preliminary efficacy, tolerability, and PK of CHS-388 in combination with toripalimab

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pembrolizumab (Monoclonal Antibodies)
• SRF388 (Monoclonal Antibodies)

Trial Overview The trial is testing SRF388 alone or with Pembrolizumab in patients with various advanced cancers. It's a first-in-human study to see how well these treatments work and what the best doses might be.

Participant Groups

Group I: Part D CHS-388 in Combination with Toripalimab Experimental Treatment 2 Interventions

Part D will evaluate the safety, preliminary efficacy, tolerability, and PK of CHS-388 in combination with toripalimab in patients with anti-PD(L)1 relapsed/refractory advanced NSCLC.

Group II: Part C CHS-388 in Combination with Pembrolizumab Experimental Treatment 2 Interventions

Part C will evaluate the safety, preliminary efficacy, tolerability, and PK of CHS-388 in combination with pembrolizumab in patients with advanced RCC or HCC, or anti-PD(L)1 relapsed/refractory advanced NSCLC.

Group III: Part B CHS-388 Monotherapy Expansion Experimental Treatment 1 Intervention

Part B monotherapy expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-388 monotherapy at the recommended phase 2 dose (RP2D) in up to 40 patients with ccRCC, up to 40 patients with HCC, and up to 40 patients with NSCLC.

Group IV: Part A Monotherapy Dose Escalation Experimental Treatment 1 Intervention

The Part A monotherapy dose escalation portion of the study will evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of CHS-388 as monotherapy in up to 30 patients with advanced solid tumors.

Who Is Running the Clinical Trial?

Coherus Biosciences, Inc.

Lead Sponsor

Trials

19

Recruited

3,700+

Surface Oncology

Lead Sponsor

Trials

6

Recruited

730+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharpe & Dohme Corp.

Collaborator

Trials

1

Recruited

260+

Findings from Research

In a phase II study involving 110 patients with advanced clear cell renal cell carcinoma (ccRCC), pembrolizumab demonstrated a 36.4% objective response rate, indicating significant antitumor activity as a first-line treatment.

The treatment was generally well-tolerated, with 30% of patients experiencing grade 3-5 adverse events, primarily colitis and diarrhea, which aligns with safety profiles observed in other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. McDermott, DF., Lee, JL., Bjarnason, GA., et al.[2022]

In the final analysis of the KEYNOTE-164 study, pembrolizumab demonstrated a 32.8% objective response rate in patients with advanced MSI-H/dMMR colorectal cancer who had received multiple prior treatments, indicating its efficacy in this difficult-to-treat population.

The treatment was associated with a median overall survival of 31.4 months for patients with more prior therapies and 47.0 months for those with fewer, while maintaining a manageable safety profile with no new safety concerns reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for previously treated, microsatellite instability-high/mismatch repair-deficient advanced colorectal cancer: final analysis of KEYNOTE-164. Le, DT., Diaz, LA., Kim, TW., et al.[2023]

In a real-life study of 108 patients with advanced non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score of ≥50%, pembrolizumab showed a median progression-free survival of 10.1 months, similar to results from the KEYNOTE-024 trial.

The treatment was generally well-tolerated, with only 8% of patients experiencing grade 3 adverse events, and no severe (grade 4 or 5) adverse events reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. Amrane, K., Geier, M., Corre, R., et al.[2021]

In a phase II trial involving 159 patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma, pembrolizumab showed significant antitumor activity, with an objective response rate of 50.0% in the locally advanced cohort and 35.2% in the recurrent/metastatic cohort.

The treatment demonstrated a manageable safety profile, with only 11.9% of patients experiencing grade 3-5 treatment-related adverse events, indicating that pembrolizumab is a promising and durable treatment option for cSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial. Hughes, BGM., Munoz-Couselo, E., Mortier, L., et al.[2022]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

References

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

Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164. [2021]

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

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for previously treated, microsatellite instability-high/mismatch repair-deficient advanced colorectal cancer: final analysis of KEYNOTE-164. [2023]

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

First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial. [2022]

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

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]

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

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. [2023]