MCLA-158 for Solid Cancers

Recruiting at 43 trial locations

Overseen By Gianluca Laus, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Merus N.V.

Must not be taking: Immunosuppressants

Disqualifiers: CNS metastases, Uncontrolled hypertension, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

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

The trial requires a washout period (time without taking certain medications) of 4 weeks or 5 half-lives, whichever is shorter, for any systemic anticancer therapy before starting the study treatment. For certain drugs with delayed toxicity, a 6-week washout period is needed. Please consult with the trial team for specific guidance on your current medications.

What makes the drug MCLA-158 unique for treating solid cancers?

MCLA-158 is unique because it is a bispecific antibody that targets both EGFR (a protein involved in cell growth) and LGR5 (a protein associated with cancer stem cells), potentially offering a novel approach by simultaneously attacking cancer cells and cancer stem cells, which may help prevent tumor growth and recurrence. ^{1 2 3 4 5}

Research Team

Gianluca Laus, MD

Principal Investigator

Merus N.V.

Eligibility Criteria

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.

Inclusion Criteria

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

I have squamous cell carcinoma of the lung.

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

Exclusion Criteria

History of hypersensitivity reaction or any toxicity attributed to human proteins or any of the excipients that warranted permanent cessation of these agents

Participation in another clinical trial or treatment with any investigational drug within 4 weeks prior to study entry

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients with metastatic CRC receive escalating doses of MCLA-158 every 2 weeks until MTD or RP2D is reached

4 weeks

Every 2 weeks

Dose Expansion

Evaluation of MCLA-158 at 1500 mg every 2 weeks in selected solid tumor indications

36 months

Every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 30 days post-last dose

Treatment Details

Interventions

• MCLA-158 (Monoclonal Antibodies)

Trial Overview 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.

Participant Groups

Group I: MCLA-158 + Pembrolizumab Experimental Treatment 1 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 + FOLFOX combination chemotherapy Experimental Treatment 1 Intervention

MCLA-158 in combination with FOLFOX will be explored in mCRC patients with up to 1 line of prior regimen.

Group III: MCLA-158 + FOLFIRI combination chemotherapy Experimental Treatment 1 Intervention

MCLA-158 in combination with FOLFIRI will be explored in mCRC patients with up to 1 line of prior regimen.

Group IV: MCLA-158 Experimental Treatment 1 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 addition, in the expansion phase, one randomized cohort will evaluate 2 doses (1100 mg and 1500 mg) of MCLA-158 in head and neck squamous cell carcinoma patients.

Who Is Running the Clinical Trial?

Merus N.V.

Lead Sponsor

Trials

10

Recruited

2,700+

Chiltern International Inc.

Industry Sponsor

Trials

16

Recruited

7,900+

Q2 Solutions

Industry Sponsor

Trials

15

Recruited

1,600+

Oncology Therapeutic Development (OTD)

Collaborator

Trials

1

Recruited

520+

4Clinics

Collaborator

Trials

1

Recruited

520+

Findings from Research

In a phase II study involving 148 patients with advanced non-small cell lung cancer, the combination of pemetrexed and the EGFR-targeting antibody matuzumab showed a higher objective response rate (11%) compared to pemetrexed alone (5%), although this difference was not statistically significant.

Patients receiving weekly matuzumab had a notably better overall survival (12.4 months) compared to those receiving it every 3 weeks (5.9 months) and those on pemetrexed alone (7.9 months), suggesting that the timing of matuzumab administration may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed with or without matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer. Schiller, JH., von Pawel, J., Schütt, P., et al.[2019]

In a phase Ib study involving 42 patients with c-Met-positive non-small-cell lung cancer (NSCLC), the combination of Telisotuzumab vedotin (Teliso-V) and erlotinib demonstrated promising antitumor activity, with a median progression-free survival (PFS) of 5.9 months and an objective response rate (ORR) of 32.1% in patients with EGFR mutations.

The treatment was generally well-tolerated, with neuropathies being the most common adverse event, affecting 57% of patients, indicating that the combination therapy has an acceptable safety profile for patients previously treated with EGFR tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein-Expressing Non-Small-Cell Lung Cancer. Camidge, DR., Barlesi, F., Goldman, JW., et al.[2023]

In a phase 3 trial involving 308 patients with advanced non-small-cell lung cancer (NSCLC) and EGFR exon 20 insertions, the combination of amivantamab and chemotherapy significantly improved progression-free survival compared to chemotherapy alone, with a median of 11.4 months versus 6.7 months.

The combination therapy also showed a higher response rate, with 73% of patients achieving a complete or partial response compared to 47% in the chemotherapy-only group, indicating that amivantamab enhances the effectiveness of standard chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. Zhou, C., Tang, KJ., Cho, BC., et al.[2023]

MEHD7945A (duligotuzumab) is an innovative immunotherapy that targets both EGFR and HER3, which are key players in tumor resistance, particularly in pancreatic cancer.

The study successfully established the pharmacokinetics and tumor accretion of a PET diagnostic agent (89Zr-MEHD7945A), confirming its specificity for the targeted receptors, which could enhance treatment monitoring and efficacy assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging EGFR and HER3 through 89Zr-labeled MEHD7945A (Duligotuzumab). McKnight, BN., Kuda-Wedagedara, ANW., Sevak, KK., et al.[2023]

188Re-MAG3-depreotide significantly inhibits the proliferation and invasion of non-small cell lung cancer (NSCLC) cells, with a notable increase in apoptosis rates (23.1% for A549 cells and 22.6% for SPC-A1 cells) observed 48 hours after treatment.

In vivo studies showed that treatment with 188Re-MAG3-depreotide markedly suppressed cancer growth compared to control groups, indicating its potential as an effective radiotherapy option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effect of 188Re-MAG3-depreotide on non-small cell lung cancer in vivo and in vitro. Yu, F., Lv, M., Cai, H., et al.[2021]

References

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

Pemetrexed with or without matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer. [2019]

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

Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein-Expressing Non-Small-Cell Lung Cancer. [2023]

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

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Imaging EGFR and HER3 through 89Zr-labeled MEHD7945A (Duligotuzumab). [2023]

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

Therapeutic effect of 188Re-MAG3-depreotide on non-small cell lung cancer in vivo and in vitro. [2021]