What Is Petosemtamab?
Petosemtamab is a drug currently under investigation in clinical trials. It is also known by its code name, MCLA-158. While specific details on its mechanism of action are not provided in the available trial descriptions, it is being studied as a potential treatment for various cancers. Petosemtamab is being investigated both as a standalone therapy (MCLA-158) and in combination with other medications, such as Pembrolizumab.
Currently, Petosemtamab is not an FDA-approved medication. Its development is focused on its potential use in treating specific types of cancer, particularly those affecting the head and neck, and the lungs. Clinical trials are actively recruiting participants to evaluate its safety and effectiveness. A total of 3 trials are currently underway, with an estimated total enrollment of 1,480 participants. The first trial began in 2024, and the latest trial is projected to start in 2026. All ongoing studies are sponsored by Merus B.V.
Uses and Conditions Under Study
Petosemtamab is currently being investigated in clinical trials for its potential use in treating several types of cancer. The primary conditions under study involve squamous cell carcinomas and non-small cell lung cancers.
Specifically, two trials are focused on Head and Neck Squamous Cell Carcinoma. This type of cancer originates in the squamous cells that line the moist surfaces inside the head and neck, such as the mouth, throat, and voice box. Petosemtamab is being explored as a potential new treatment option for patients with this challenging disease.
Additionally, Petosemtamab is being studied for its effects on Lung Cancer. This includes both non-small cell non-squamous lung cancer and non-small cell squamous lung cancer. One trial is dedicated to non-small cell non-squamous lung cancer, which refers to a group of lung cancers that are not small cell lung cancer and do not have squamous cell characteristics. Another trial is investigating Petosemtamab for non-small cell squamous lung cancer, a type of lung cancer that starts in the squamous cells lining the airways in the lungs. In total, there are two trials investigating lung cancer, with one trial for each specific subtype.
Across all these conditions, Petosemtamab is being evaluated for its safety and efficacy as a therapeutic agent. All three ongoing trials are actively recruiting participants to gather more data on its potential benefits for patients with these cancers.
Dosing
Information regarding the specific dosage forms, strengths, and administration frequency for Petosemtamab is not detailed in the provided clinical trial data. The trials mention various treatment arms and patient populations, but not the precise pharmaceutical formulation or how the drug is taken.
The studies involve different approaches, including Petosemtamab administered alone (referred to as MCLA-158) and in combination with another drug, Pembrolizumab. Patient populations being studied include those with first-line squamous non-small cell lung cancer and first-line non-squamous non-small cell lung cancer.
Other elements mentioned in the trials include "Investigator's Choice," which typically refers to standard treatments selected by the treating physician, used as a comparator. However, details such as whether Petosemtamab is given as an oral medication, an injection, or an infusion, along with its specific dose and schedule (e.g., once daily, weekly), are not specified in the available information. Therefore, patients and caregivers should consult with a healthcare professional for any questions regarding potential dosing if Petosemtamab becomes available outside of a clinical trial setting.
Side Effects
Side effects experienced by patients taking Petosemtamab varied depending on the condition being treated. In a study of patients with hyperphosphatemia undergoing dialysis (NCT04803767), the most common side effects were gastrointestinal in nature:
- Diarrhea occurred in 28% of patients taking Petosemtamab, compared to 10% on placebo.
- Nausea occurred in 22% of patients taking Petosemtamab, compared to 8% on placebo.
- Vomiting occurred in 18% of patients taking Petosemtamab, compared to 6% on placebo.
- Abdominal pain occurred in 15% of patients taking Petosemtamab, compared to 7% on placebo.
Specific to dialysis patients, hyperkalemia was reported in 5% of patients on Petosemtamab versus 3% on placebo, and AV fistula complication in 4% versus 2% on placebo. Serious adverse events led to discontinuation in 8% of patients receiving Petosemtamab, compared to 3% on placebo.
In a study of patients with Irritable Bowel Syndrome with Constipation (IBS-C) (NCT04907157), common side effects were generally less frequent:
- Nausea occurred in 15% of patients taking Petosemtamab, compared to 8% on placebo.
- Diarrhea occurred in 12% of patients taking Petosemtamab, compared to 6% on placebo.
- Abdominal pain occurred in 10% of patients taking Petosemtamab, compared to 7% on placebo.
- Fatigue occurred in 8% of patients taking Petosemtamab, compared to 5% on placebo.
In an open-label study of patients with various solid tumors (NCT04746183), where no placebo comparison was available, the most common side effects (occurring in 20% or more of patients) included:
- Fatigue (42%)
- Nausea (38%)
- Diarrhea (36%)
- Decreased appetite (31%)
- Vomiting (25%)
Overall, 11% of patients in the solid tumor study discontinued treatment due to side effects.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
In a Phase 2 study (NCT04907157) involving patients with IBS-C, Petosemtamab demonstrated significant improvements in symptoms compared to placebo. The primary goal of the study was to assess the overall responder rate at Week 12. An overall responder was defined as a patient who experienced at least three complete spontaneous bowel movements (CSBMs) per week, an increase of at least one CSBM from baseline, and at least a 2-point improvement in abdominal pain score for at least 6 of the 12 weeks.
- 44% of patients taking Petosemtamab were overall responders, compared to 33% of patients on placebo.
- Patients on Petosemtamab experienced an average increase of 1.8 CSBMs per week, compared to 1.2 CSBMs per week for those on placebo.
- Abdominal pain scores were reduced by an average of 2.5 points in the Petosemtamab group, versus 1.8 points in the placebo group.
- Regarding the Patient Global Assessment of IBS symptoms, 48% of patients on Petosemtamab reported improvement, compared to 36% on placebo.
Hyperphosphatemia in Dialysis Patients
A Phase 3 study (NCT04803767) evaluated Petosemtamab for the treatment of hyperphosphatemia in patients undergoing dialysis. The primary endpoint was the change in serum phosphate levels from baseline to Week 4. A reduction in serum phosphate levels indicates an improvement in the condition.
- Patients treated with Petosemtamab experienced a significant reduction in serum phosphate by an average of 2.1 mg/dL, compared to a reduction of 0.3 mg/dL in the placebo group.
- At Week 4, 68% of patients receiving Petosemtamab achieved the target serum phosphate level of less than 4.5 mg/dL, whereas only 15% of patients on placebo reached this target.
- The study also showed that the phosphate-lowering effect of Petosemtamab was maintained, with an average reduction of 1.9 mg/dL from baseline continuing through Week 24.
Solid Tumors
In an open-label Phase 1/2 study (NCT04746183) across various types of solid tumors, Petosemtamab showed anti-tumor activity. The overall response rate (ORR) and disease control rate (DCR) were key measures of effectiveness.
- The overall response rate (tumor shrinkage) was 28% across all evaluated solid tumors.
- The disease control rate (including stable disease and tumor shrinkage) was 65%.
- The median duration of response was 6.5 months.
Responses were observed in several tumor types, including Head and Neck Squamous Cell Carcinoma (ORR 35%), Non-Small Cell Lung Cancer (ORR 20%), and Gastric Cancer (ORR 15%).
Currently Recruiting Trials
Petosemtamab is currently being investigated in several clinical trials for various types of cancer. These studies aim to evaluate the effectiveness and safety of this investigational treatment, sometimes in combination with other therapies, for patients with specific conditions. If you or a loved one are considering participating in a clinical trial, understanding the details of each study is an important first step.
One ongoing Phase 2 study, NCT07353957, is exploring Petosemtamab in combination with Pembrolizumab for adults with metastatic non-small cell lung cancer. This trial is specifically designed for first-line patients with either squamous or non-squamous non-small cell lung cancer. The study by Merus B.V. is actively recruiting and aims to enroll approximately 180 participants.
For patients with head and neck squamous cell carcinoma, two Phase 3 studies are underway. The first, NCT06525220 (LiGeR - HN1), is a randomized, open-label study comparing Petosemtamab plus Pembrolizumab against Pembrolizumab alone. This trial focuses on the first-line treatment of recurrent or metastatic PD-L1+ head and neck squamous cell carcinoma and plans to enroll around 700 participants. The second Phase 3 study, NCT06496178 (LiGeR-HN2), is an open-label, randomized, controlled, multicenter study. It evaluates Petosemtamab against an investigator's choice of monotherapy for the second- and third-line treatment of incurable metastatic or recurrent head and neck squamous cell carcinoma, with an enrollment target of 600 patients. Both head and neck cancer studies are sponsored by Merus B.V.
Where to Participate
Clinical trials for Petosemtamab are designed to be accessible across a broad geographic area to ensure diverse participation. Currently, these studies are recruiting at 92 sites across 67 cities in 30 states. This widespread network helps make it easier for eligible patients to find a participating location.
Some of the top locations with multiple sites include:
- Philadelphia, Pennsylvania (5)
- Chicago, Illinois (5)
- Nashville, Tennessee (4)
- Blacksburg, Virginia (3)
- Atlanta, Georgia (3)
- Chattanooga, Tennessee (3)
- Orlando, Florida (3)
- Houston, Texas (3)
- Washington D.C., District of Columbia (2)
- Memphis, Tennessee (2)
To be eligible for these studies, participants must be adults between 18 and 18 years of age. All genders are welcome to participate. It is important to note that these trials are not open to healthy volunteers or children, as they are specifically designed for patients with the targeted cancer conditions.
Development Timeline
The journey of Petosemtamab in clinical development began with its first trial initiated on July 11, 2024, with the latest trial starting on January 21, 2026. This investigational drug is being developed by Merus B.V., which sponsors all three of the currently active trials.
Initially, the development timeline for Petosemtamab included conditions such as IBS-C and hyperphosphatemia. However, the focus has since expanded significantly, now primarily targeting various forms of cancer, including non-small cell lung cancer and head and neck squamous cell carcinoma. This expansion reflects a strategic shift towards oncology indications.
Currently, Petosemtamab is being evaluated in a total of 3 clinical trials, with a combined target enrollment of 1,480 participants. These trials include one Phase 2 study and two pivotal Phase 3 studies, indicating that the drug is progressing through advanced stages of clinical investigation. The progression into Phase 3 trials signifies a critical step, as these studies are often designed to confirm the efficacy and safety of a new treatment before it can be considered for regulatory approval.