What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) involving EGFR inhibition, such as erlotinib and gefitinib, often result in side effects like rash, diarrhea, and liver enzyme abnormalities. Chemotherapy agents, including carboplatin and paclitaxel, are associated with nausea, vomiting, hair loss, and myelosuppression. Immunotherapy treatments, such as pembrolizumab, can lead to immune-related adverse events like pneumonitis, colitis, and thyroid dysfunction. These side effects are important considerations when evaluating treatment options for NSCLC.

What prior FDA approvals exist?

Several FDA-approved treatments for Non-Small Cell Lung Cancer (NSCLC) involve EGFR inhibition, similar to the MCLA-158 trial. These include drugs like erlotinib, gefitinib, afatinib, and osimertinib, which target the EGFR mutation commonly found in NSCLC patients. These treatments have shown efficacy in improving progression-free survival in patients with EGFR-mutant NSCLC. Additionally, other FDA-approved treatments for NSCLC include immune checkpoint inhibitors such as pembrolizumab and atezolizumab, which have been approved for use in combination with chemotherapy for advanced stages of the disease.

What other types of research exist?

Promising alternatives to MCLA-158 for NSCLC patients include next-generation ALK inhibitors, which have shown improved potency against ALK rearrangements and resistance. Additionally, immune checkpoint inhibitors like pembrolizumab and nivolumab, which target PD-1/PD-L1 pathways, have demonstrated significant efficacy in advanced NSCLC. Novel irreversible EGFR inhibitors, such as 324674, which effectively block EGFR activation and downstream signaling pathways, also present a promising option.

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Monoclonal Antibodies

MCLA-158 for Solid Cancers

Phase 1 & 2

Recruiting

Research Sponsored by Merus N.V.

Eligibility Criteria Checklist

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

Must have

Histologically or cytologically confirmed solid tumors with evidence of metastatic or locally advanced disease not amenable to standard therapy with curative intent

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Must not have

Any systemic anticancer therapy within 4 weeks or 5 half-lives whichever is longer of the first dose of study treatment

Major surgery or radiotherapy within 3 weeks of the first dose of study treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6-12 months

Awards & highlights

Summary

This trial is testing a new drug called MCLA-158 to see if it can help treat certain cancers by blocking a protein that helps cancer cells grow. It focuses on patients with cancers that rely on this protein, like colorectal and head and neck cancers.

Who is the study for?

This trial is for adults with advanced solid tumors like lung, stomach, colorectal cancers that can't be cured by standard treatments. They must have a fresh tumor sample available and measurable disease. Good physical condition (ECOG 0 or 1) and proper organ function are required. Exclusions include recent major surgery, heart issues, other malignancies within 3 years, active infections, or uncontrolled medical conditions.

What is being tested?

The study tests MCLA-158 in patients with metastatic colorectal cancer (mCRC) and other solid tumors dependent on EGFR inhibition. It's an open-label trial to determine the safest dose of MCLA-158 that also works best (RP2D). The study will evaluate safety, how the body processes the drug (PK/PD), immune response to it (immunogenicity), and its effectiveness against tumors.

What are the potential side effects?

While specific side effects for MCLA-158 aren't listed here as it's early in testing, similar drugs often cause reactions at injection sites, flu-like symptoms such as fever and chills, fatigue, nausea or diarrhea. There may also be risks of allergic reactions or effects on liver function which will be closely monitored.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has spread and cannot be cured with standard treatments.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I can provide a recent tumor sample from the primary or metastatic site.

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My cancer in the head, neck, stomach, or gastroesophageal junction is EGFR positive.

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I can undergo a biopsy.

Exclusion Criteria

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

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I haven't had cancer treatment in the last 4 weeks or longer.

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I haven't had major surgery or radiotherapy in the last 3 weeks.

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I have serious heart issues, but not atrial fibrillation or sudden fast heartbeats.

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I am currently taking medication to suppress my immune system.

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I have active hepatitis B and am not on antiviral treatment.

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I have a history of lung disease or signs of it on a chest scan.

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My liver disease is severe, and my cancer type is specific and aggressive.

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I have had a heart attack in the last 6 months.

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My brain metastases are either untreated, causing symptoms, or need treatment to manage symptoms.

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My cancer has spread to the lining of my brain and spinal cord.

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My blood pressure is high (>150/100 mmHg) despite treatment, or I have unstable chest pain.

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I need oxygen therapy all the time due to difficulty breathing.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6-12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6-12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6-12 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

Escalation: Number of patients with Dose Limiting Toxicities (DLTs) during Cycle 1

Expansion (Single agent, randomized expansion in 2/3L Head and Neck cancer and combination cohorts): Safety and tolerability: AEs and SAEs

Expansion (Single agent, randomized expansion in 2/3L Head and Neck cancer): Treatment discontinuations and dose modifications due to AEs

+3 more

Secondary study objectives

Escalation & Expansion (single agent - non-randomized and Combination cohorts): Treatment discontinuations and dose modifications due to AEs

Escalation & Expansion (single agent - non-randomized): Safety and tolerability: AEs and SAEs

Escalation & Expansion (single agent, non-randomized cohort): Cytokine Panel Expression Profile

+26 more

Other study objectives

Escalation & Expansion: Biomarkers for Wnt signaling proteins

Escalation & Expansion: Biomarkers for differential expression of mRNA

Escalation & Expansion: Biomarkers for differential expression of miRNA

+1 more

Trial Design

3Treatment groups

Experimental Treatment

Group I: MCLA-158 + PembrolizumabExperimental Treatment1 Intervention

MCLA-158 in combination with pembrolizumab will be explored first in head and neck squamous cell carcinoma patients eligible to receive pembrolizumab as first-line monotherapy.

Group II: MCLA-158 + FOLFIRI combination chemotherapyExperimental Treatment1 Intervention

MCLA-158 in combination with FOLFIRI combination will be explored first in metastatic colorectal cancer patients (mCRC) in the 2L setting.

Group III: MCLA-158Experimental Treatment1 Intervention

In Part 1, the dose escalation phase, patients with metastatic CRC will receive escalating doses of MCLA-158 (every 2 weeks) until MTD or RP2D is reached. Each Cycle is 28 days. Single agent treatment. In Part 2, the expansion phase, participants with metastatic CRC and certain other solid tumors will receive intravenous infusion of MCLA-158 at the recommended Phase II dose (RP2D) every 2 weeks, at Day 1 and Day 15. The duration of each treatment cycle is 28 days. In the expansion phase, 2 doses (1100 mg and 1500 mg) of MCLA-158 will be evaluated in a cohort of head and neck squamous cell carcinoma patients

0 / 17Eligibility 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 Non-Small Cell Lung Cancer (NSCLC) include targeted therapies, immunotherapies, and chemotherapy. Targeted therapies, such as EGFR inhibitors, work by blocking the epidermal growth factor receptor (EGFR) pathway, which is often overactive in NSCLC cells, leading to uncontrolled growth and proliferation. This is particularly relevant for patients with EGFR mutations, as these inhibitors can significantly slow disease progression. Immunotherapies, like PD-1/PD-L1 inhibitors, enhance the body's immune response against cancer cells. Chemotherapy, using drugs like pemetrexed and carboplatin, kills rapidly dividing cells, including cancer cells. Understanding these mechanisms helps tailor treatments to individual patients, improving outcomes and minimizing side effects.

New targeted treatments in lung cancer--overview of clinical trials.