What side effects are associated with this type of intervention?

Common treatments for Renal Cell Carcinoma (RCC) include monoclonal antibodies, VEGFR inhibitors, and checkpoint inhibitors. Monoclonal antibodies, such as those targeting IL-27, can cause side effects like infusion reactions, cytokine release syndrome, and potential renal toxicity. VEGFR inhibitors often lead to hypertension, hand-foot syndrome, and gastrointestinal issues. Checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 therapies, can result in immune-related adverse events including colitis, pneumonitis, and endocrinopathies. These treatments require careful monitoring to manage and mitigate side effects.

What prior FDA approvals exist?

Several FDA-approved treatments for Renal Cell Carcinoma (RCC) include monoclonal antibodies and immunotherapies. Pembrolizumab, an anti-PD-1 monoclonal antibody, has shown efficacy in metastatic sarcomatoid RCC. Nivolumab, another anti-PD-1 antibody, is approved for advanced RCC and is often used in combination with ipilimumab, an anti-CTLA-4 antibody. Additionally, bevacizumab, an anti-VEGF monoclonal antibody, is used in combination with atezolizumab, an anti-PD-L1 antibody, for advanced RCC. These treatments are similar to CHS-388 in that they involve monoclonal antibodies targeting specific pathways in the immune system.

What other types of research exist?

A promising alternative to CHS-388 for Renal Cell Carcinoma patients is CDX-014, an antibody-drug conjugate directed against TIM-1, which has shown safety and preliminary activity in a phase I trial for advanced refractory RCC.

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Monoclonal Antibodies

SRF388 + Pembrolizumab for Cancer

Phase 1

Recruiting

Research Sponsored by Coherus Biosciences, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with NSCLC must have histologically confirmed locally advanced and/or metastatic Stage IV NSCLC

For patients with HCC, Child-Pugh Class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)

Must not have

Previously received an anti-IL-27 antibody or anti-IL-27 targeted therapy

Major surgery within 4 weeks prior to Screening

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions at the infusion site, fatigue, changes in liver enzymes or blood counts that could indicate liver or bone marrow issues, and potential immune system-related adverse events.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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My liver cancer has a measurable tumor according to specific criteria.

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I have a measurable tumor in my kidney, liver, or lung cancer.

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I have advanced kidney or liver cancer treated before, or my lung cancer can't be removed by surgery.

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My cancer has worsened despite treatment with SRF388.

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My NSCLC has worsened despite recent treatment.

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My blood counts meet the required levels for treatment.

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

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I've had 3 or fewer treatments for my cancer that can't be removed by surgery, including chemotherapy and immunotherapy.

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I am fully active or can carry out light work.

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I have not had severe side effects from SRF388 treatment.

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My kidney function, measured by creatinine or GFR, is within the required range.

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My liver cancer cannot be surgically removed and is at an advanced stage.

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I am 18 years old or older.

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I am fully active or can carry out light work.

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My kidney function, measured by creatinine clearance, is within the required range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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I can't have certain scans for my liver cancer due to an allergy or other issue.

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I haven't had drug treatments for cancer that can't be surgically removed or has spread.

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My liver cancer is not purely hepatocellular.

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

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I have received an organ or tissue transplant from another person.

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My liver cancer is either fibrolamellar or mixed hepatocellular-cholangiocarcinoma type.

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Over half of my liver is affected by cancer.

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I had a bone marrow transplant less than 6 months ago or have graft-versus-host disease.

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I have liver cancer with noticeable swelling in my abdomen.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

[Part A] Dose Limiting Toxicity (DLT)

[Part B] Confirmed objective response rate (ORR)

[Part C -NSCLC Cohort] Objective response rate (ORR)

+3 more

Secondary study objectives

[Part A, Part B, Part C, Part D] Disease control rate (DCR)

[Part A, Part B, Part C, Part D] Duration of response (DoR)

[Part A, Part B, Part C, Part D] Progression-free survival (PFS)

+10 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Part D CHS-388 in Combination with ToripalimabExperimental Treatment2 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 PembrolizumabExperimental Treatment2 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 ExpansionExperimental Treatment1 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 EscalationExperimental Treatment1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Toripalimab

2017

Completed Phase 3

~1260

Pembrolizumab

2017

Completed Phase 3

~3130

0 / 28Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Renal Cell Carcinoma (RCC) include tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and monoclonal antibodies. TKIs, such as sunitinib, inhibit pathways that promote tumor growth and angiogenesis. Immune checkpoint inhibitors, like nivolumab and pembrolizumab, block proteins (PD-1/PD-L1) that prevent the immune system from attacking cancer cells. Monoclonal antibodies, such as the one targeting IL-27 in the CHS-388 trial, aim to modulate the immune response against cancer cells. These treatments are crucial for RCC patients as they offer targeted approaches to slow disease progression and potentially improve survival rates.

Non-clear cell renal cell carcinomas: biological insights and therapeutic challenges and opportunities.Intrinsic immune alterations in renal cell carcinoma and emerging immunotherapeutic approaches.Can vaccination or tyrosine kinase inhibitor therapy play a role in the adjuvant treatment of renal cell carcinoma?