Phase 1/2 dose escalation and cohort expansion study evaluating MCLA-158 (Petosemtamab) as single agent or in combination in advanced solid tumors

Phase 2

Recruiting

• Conditions: advanced solid tumors; 10027655

• Registration Number: NL-OMON56321
• Lead Sponsor: Merus N.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 34

Inclusion Criteria

1. Signed ICF before initiation of any study procedures
2. Age >=18 years at signing of ICF
3. Histologically or cytologically confirmed solid tumors with evidence of
metastatic or locally advanced disease not amenable to standard therapy with
curative intent:
• Expansion cohorts: patients with locally advanced unresectable or metastatic
disease for the following indications:
SINGLE AGENT
o 2L/3L HNSCC PATIENTS: patients who have progressed on or after, or are
intolerant to, anti-PD-(L)1 and platinum therapy as monotherapy or in
combination with other agents and no previous exposure to EGFR inhibitors.
Patients treated with platinum-containing therapy only in the adjuvant setting,
or in the context of multimodal therapy for locally advanced disease, should
have disease progression within 6 months of the last dose of platinum
containing therapy. Patients should not have received more than 2 prior lines
of treatment in recurrent or metastatic disease.
* Human papillomavirus (HPV) status determined by p16 IHC or molecular HPV test
for all oropharyngeal tumors should be reported when available.
* The eligible HNSCC primary tumor locations are oropharynx, oral cavity,
hypopharynx, and larynx.
o Cancers of the anogenital tract with squamous cell histology (ie, cervical,
vaginal, vulvar, penile, anal)
o Skin SCC
o NSCLC non-SCC and NSCLC SCC
o GEA with histologically confirmed EGFR amplification (fluorescence in situ
hybridization [FISH] score EGFR/ chromosome 7 (CEP7) ratio >=2.0, or tumor NGS
EGFR copy >=8, or ctDNA >=4, or EGFR IHC H-score >=200)
o PA
o mCRC in 3L+: Patients should be free of mutations in RAS family genes (i.e.
KRAS, NRAS, Harvey Rat Sarcoma virus [HRAS], or RAF family genes (i.e. BRAF,
A-Rapidly Accelerated Fibrosarcoma [ARAF}, Rapidly Accelerated Fibrosarcoma-1
[RAF1]), determined by central ctDNA NGS prescreening]). Note: If the patient
was treated with an EGFR inhibitor in 1L or 2L, then the patient should have
shown CR/PR. In addition, the patient at study entry should have at least 6
months of interval since the last administration of EGFR inhibitor.
Other indications may be considered, such as malignant salivary gland tumors.
• Note 1: Patients with NSCLC must receive all recommended standard therapies
driven by the histological subtype and tumor molecular profile.
• Note 2: Patients with other indications must have been previously treated
with 1 or 2 lines of the standard approved therapy (when applicable) in the
locally advanced/unresectable or metastatic setting.
COMBINATION
o 1L HNSCC: patients eligible to receive pembrolizumab as 1L monotherapy with
tumors expressing PD-L1, CPS >=1, as determined by an FDA-approved test in the
US, or by an approved equivalent test in other countries; patients should not
have previous systemic therapy administered in the recurrent or metastatic
setting, although previous systemic therapy as part of multimodal treatment for
locally advance disease is allowed if ended >=6 months prior to signing the ICF.
The eligible HNSCC primary tumor locations are oropharynx, oral cavity,
hypopharynx, and larynx. Previous treatments with anti-PD-(L)1 or anti-EGFR
therapies are not allowed.
o 2L mCRC: Patients should have been previously diagnosed with histologically
or cytologically confirmed unresectable o

Exclusion Criteria

1. Central nervous system metastases that are untreated or symptomatic, or
require radiation, surgery, or continued steroid therapy to control symptoms
within 14 days of study entry
2. Known leptomeningeal involvement
3. Participation in another clinical trial or treatment with any
investigational drug within 4 weeks prior to study entry
4. Any systemic anticancer therapy within 4 weeks or 5 half-lives, whichever is
shorter, of the first dose of study treatment. For cytotoxic agents that have
major delayed toxicity (eg, mitomycin C, nitrosoureas), or anticancer
immunotherapies, a washout period of 6 weeks is required.
5. Requirement for immunosuppressive medication (eg, methotrexate,
cyclophosphamide)
6. Major surgery or radiotherapy within 3 weeks of the first dose of study
treatment. Patients who received prior radiotherapy to >=25% of bone marrow are
not eligible, irrespective of when it was received.
7. Persistent Grade >1 clinically significant toxicities related to prior
antineoplastic therapies (except for alopecia); stable sensory neuropathy Grade
<=2 National Cancer Institute-Common Terminology Criteria for Adverse Events
(NCI-CTCAE) v4.03 is allowed.
8. History of hypersensitivity reaction to any of the excipients of
petosemtamab, human proteins, or any non-IMP treatment required for this study
9. Uncontrolled hypertension (systolic BP >150 mmHg and/or diastolic BP >100
mmHg) with appropriate treatment; unstable angina; history of congestive heart
failure of Class II-IV New York Heart Association (NYHA) criteria, or serious
cardiac arrhythmia requiring treatment (except atrial fibrillation, paroxysmal
supraventricular tachycardia); or history of myocardial infarction within 6
months of study entry
10. History of prior malignancies with the exception of excised cervical
intraepithelial neoplasia or nonmelanoma skin cancer, or curatively treated
cancer deemed at low risk for recurrence with no evidence of disease for >=3
years.
11. Current dyspnea at rest of any origin, or other diseases requiring
continuous oxygen therapy, including patients with a history of ILD (eg,
pneumonitis or pulmonary fibrosis), or evidence of ILD on baseline chest
computerized tomography (CT) scan
12. Current serious illness or medical conditions including, but not limited
to, uncontrolled active infection, clinically significant pulmonary, metabolic,
or psychiatric disorders
13. Patients with known infectious diseases:
• Active hepatitis B infection (hepatitis B surface antigen [HbsAg] positive)
without receiving antiviral treatment. Note:
o Patients who are HbsAg positive must receive antiviral treatment with
lamivudine, tenofovir, entecavir, or other antiviral agents, starting at least
>=7 days before the initiation of study treatment.
o Patients with antecedents of hepatitis B (eg, anti-hepatitis B core
(anti-HBc) positive, HbsAg, and hepatitis B virus [HBV]-DNA negative) are
eligible.
• Positive test for hepatitis C virus (HCV) RNA. Note: Patients in whom HCV
infection resolved spontaneously (ie, positive HCV antibodies without
detectable HCV RNA), or who achieved a sustained response after antiviral
treatment and show absence of detectable HCV RNA >=6 months (with the use of
interferon [IFN]-free regimens) or >=12 months (with the use of IFN-based
regimen

Study & Design

• Study Type: Interventional
• Study Design: Not specified