MCLA-158 for Solid Cancers

Recruiting at 46 trial locations

Overseen By Gianluca Laus, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merus N.V.

Must not be taking: Immunosuppressants

Disqualifiers: CNS metastases, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

523 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test MCLA-158, a new treatment for certain solid cancers, including head and neck cancer and metastatic colorectal cancer (mCRC). The researchers will evaluate the safety and effectiveness of MCLA-158 alone and in combination with other treatments. They seek patients with advanced solid tumors that cannot be treated with standard therapies. Ideal participants have been diagnosed with metastatic colorectal cancer or head and neck cancer and have not previously received certain types of cancer treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that MCLA-158, also known as petosemtamab, appears safe for treating certain cancers. In earlier studies, patients with advanced colorectal cancer and head and neck cancer received MCLA-158, and most tolerated it well without serious side effects.

For those taking MCLA-158 with pembrolizumab, a treatment already used for some cancers, safety results were also positive. Patients responded well, and no unexpected safety problems occurred.

When combined with chemotherapy treatments like FOLFIRI and FOLFOX, MCLA-158 maintained stable safety. Research suggests that MCLA-158 can be safely added to these chemotherapy treatments, which is important because adding a new drug can sometimes increase side effects.

Overall, while any treatment can have risks, studies so far suggest MCLA-158 is generally safe for patients. It's always important to discuss potential side effects and benefits with healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MCLA-158 because it targets cancer stem cells, which are often responsible for cancer growth and resistance to treatment. This is different from most current treatments for solid cancers, like chemotherapy, which generally attack rapidly dividing cells but might not effectively target these stem cells. Additionally, MCLA-158 is being tested in combination with pembrolizumab and certain chemotherapy regimens like FOLFIRI and FOLFOX, potentially enhancing its effectiveness against challenging cancers like metastatic colorectal cancer (mCRC) and head and neck squamous cell carcinoma. These combinations could provide a more comprehensive attack on the cancer, offering hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research shows that MCLA-158, also known as petosemtamab, holds promise for treating metastatic colorectal cancer (mCRC). In this trial, participants may receive MCLA-158 alone or with chemotherapy treatments like FOLFOX and FOLFIRI. Studies have shown that when combined with FOLFOX or FOLFIRI, it achieved a 100% response rate in initial treatments for left-sided mCRC and a 62% response rate in later treatments for both left- and right-sided mCRC. Additionally, for head and neck cancers, MCLA-158 combined with pembrolizumab targets proteins called EGFR and LGR5, which promote cancer growth, suggesting potential effectiveness for these cancers as well. This treatment remains under study, but early results are encouraging for these types of solid tumors. ^{1 2 3 4 5}

Who Is on the Research Team?

Gianluca Laus, MD

Principal Investigator

Merus N.V.

Are You a Good Fit for This Trial?

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• MCLA-158

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. ir.merus.nl ir.merus.nl/news-releases/news-release-details/merus-interim-data-petosemtamab-metastatic-colorectal-cancer

News Release “These data demonstrate petosemtamab's clinical activity beyond head and neck squamous cell carcinoma. ... Petosemtamab (MCLA-158: EGFR x LGR5 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12110399/

Petosemtamab, a Bispecific Antibody Targeting Epidermal ... This review focuses on the role of LGR5 in cancer biology, experiments leading to the selection of the EGFR×LGR5 BsAb petosemtamab as having the ...

3. biospace.com biospace.com/press-releases/merus-interim-data-on-petosemtamab-in-metastatic-colorectal-cancer-demonstrates-monotherapy-activity-and-robust-response-rate-in-combination-with-folfox-folfiri-with-well-tolerated-safety

Merus' Interim Data on Petosemtamab in Metastatic ... “These data demonstrate petosemtamab's clinical activity beyond head and neck squamous cell carcinoma. ... Petosemtamab (MCLA-158: EGFR x LGR5 ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT03526835

A Study of Bispecific Antibody MCLA-158 in Patients With ... An updated analysis of the interim clinical data from the phase 2 trial of petosemtamab with pembrolizumab as 1L treatment of PD-L1+ recurrent/metastatic (r/m) ...

5. globenewswire.com globenewswire.com/news-release/2025/10/24/3172890/0/en/Merus-Interim-Data-on-Petosemtamab-in-Metastatic-Colorectal-Cancer-Demonstrates-Monotherapy-Activity-and-Robust-Response-Rate-in-Combination-with-FOLFOX-FOLFIRI-with-Well-Tolerated.html

Merus' Interim Data on Petosemtamab in Metastatic “These data demonstrate petosemtamab's clinical activity beyond head and neck squamous cell carcinoma. ... Petosemtamab (MCLA-158: EGFR x LGR5 ...