Phase 1/2 dose escalation and expansion study evaluating MCLA-129, a human anti-EGFR and anti-c-MET bispecific antibody, in patients with advanced NSCLC and other solid tumors
- Conditions
- Lung CancerSolid tumors10027655
- Registration Number
- NL-OMON52004
- Lead Sponsor
- Merus N.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 30
1. Signed informed consent before initiation of any study procedures.
2. Age >= 18 years at signature of informed consent.
3. Histologically or cytologically confirmed solid tumors with evidence of
metastatic or locally advanced unresected disease that is incurable.
4. Availability of archival or a fresh tumor tissue sample.
5. Measurable disease as defined by RECIST version 1.1 by radiologic methods.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Life expectancy >= 12 weeks, as per Investigator.
8. Adequate organ function.
1. Central nervous system metastases that are untreated or symptomatic, or
require radiation, surgery, or continued steroid therapy (> 10 mg prednisone or
equivalent) to control symptoms within 14 days of study entry.
2. Known leptomeningeal involvement.
3. Participation in another clinical study or treatment with any
investigational drug within 4 weeks prior to study entry.
4. Prior treatment with a bispecific EGFR-c-MET antibody.
5. Systemic anticancer therapy or immunotherapy within 4 weeks or 5 half-lives,
whichever is shorter, of the first dose of study drug. For cytotoxic agents
that have major delayed toxicity (e.g., mitomycin C, nitrosoureas), a washout
period of 6 weeks is required. Note: For agents with long half-lives,
enrollment before the fifth half-life requires Sponsor approval.
6. Major surgery or radiotherapy within 3 weeks of the first dose of study
drug. Patients who received prior radiotherapy to >=25% of bone marrow at any
time are not eligible.
7. Persistent grade >1 clinically significant toxicities related to prior
antineoplastic therapies (except for alopecia); stable sensory neuropathy <=
grade 2 NCI-CTCAE v5.0 and hypothyroidism <= grade 2 which is stable on hormone
replacement are allowed.
8. History of hypersensitivity reaction or any toxicity attributed to human
proteins or any of the excipients that warranted permanent cessation of these
agents.
9. History of clinically significant cardiovascular disease.
10. History of interstitial lung disease including drug-induced interstitial
lung disease, radiation pneumonitis that requires treatment with prolonged
steroids or other immune suppressive agents within 1 year.
11. Previous or concurrent malignancy, excluding non-basal cell carcinomas of
skin or carcinoma in situ of the uterine cervix, unless the tumor was treated
with curative or palliative intent and in the opinion of the Investigator, with
Sponsor agreement, the previous or concurrent malignancy condition does not
affect the assessment of safety and efficacy of the study drug.
12. Current dyspnea at rest of any origin, or other diseases requiring
continuous oxygen therapy.
13. Current serious illness or medical conditions including, but not limited to
uncontrolled active infection, clinically significant pulmonary, metabolic or
psychiatric disorders.
14. Active Hepatitis B infection (HBsAg positive) without receiving antiviral
treatment. Note: Patients with active hepatitis B (HbsAg positive) must receive
antiviral treatment with lamivudine, tenofovir, entecavir, or other antiviral
agents, starting at least >= 7 days before the initiation of the study
treatment. Patients with antecedents of Hepatitis B (anti-HBc positive, HbsAg
and HBV-DNA negative) are eligible.
15. Positive test for Hepatitis C ribonucleic acid (HCV RNA); Note: Patients in
whom HCV infection resolved spontaneously (positive HCV antibodies without
detectable HCV-RNA) or those who achieved a sustained virological response
after antiviral treatment and show absence of detectable HCV RNA >= 6 months
(with the use of IFN-free regimens) or >= 12 months (with the use of IFN-based
regimens) after cessation of antiviral treatment are eligible.
16. Known history of HIV (HIV 1/2 antibodies). HIV testing is not required
unless mandated by local health authority or
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase 1: Incidence and severity of DLTs during Cycle 1.<br /><br><br /><br>Phase 2: ORR per RECIST v.1.1 based on Investigator assessment</p><br>
- Secondary Outcome Measures
Name Time Method