Phase 1/2 study of MCLA-129 in patients with NSCLC and other solid tumors.

Phase 1

• Conditions: advanced NSCLC and other solid tumors; MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10049280Term: Solid tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-000203-20-NL
• Lead Sponsor: Merus N.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-02-14
• Last Update Posted: 4 March 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 460

Inclusion Criteria

1. Signed informed consent before initiation of any study procedure.s.
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:

Dose Escalation Part - Patients who have failed prior standard first-line treatment. Patients must have progressed on or be intolerant to therapies that are known to provide clinical benefit. There is no limit to the number of prior treatment regimens. Patients must have:
- Non-small cell lung cancer (NSCLC) harboring activating EGFR mutations including tyrosine kinase inhibitor (TKI) sensitizing mutations (e.g., 19del and L858R), and/or approved TKI-resistance mutations (e.g., acquired TKI-resistance mutations, i.e., T790M, C797S, L792, L798I, exon 20 insertion), or any activating c-MET mutation/amplification (e.g., high-level c-MET amplification [MET/CEP7 > 5 or cfDNA = 2 copies], or c-MET exon 14 skipping mutation).
- Gastric/gastroesophageal junction (GC/GEJ) adenocarcinoma harboring an EGFR amplification (EGFR/CEP7 =2 or cfDNA = 8 copies) or c-MET amplification (MET/CEP7 > 5 or cfDNA = 2 copies).
- Head and neck squamous cell cancer (HNSCC) or esophageal squamous cell cancer (ESCC).

Dose Expansion Part - Patients must have:
• Cohort A:
- NSCLC harboring an EGFR exon 20 insertion, that has progressed after platinum doublets (a limited number of first line patients can be included)
• Cohort B:
- NSCLC harboring c-MET exon 14 skipping mutation =2L
- Naive or pretreated to capmatinib and tepotinib
• Cohort C:
- Selected solid tumors (GC/GEJ/pancreas/ESCC, GBM and PRCC) harboring an EGFR or c-MET alteration
- NSCLC patients with other EGFR/c-MET alterations, not otherwise included in the other cohorts
- Patients must have exhausted or be intolerant to all approved therapies with rationale for clinical benefit with MCLA-129
• Cohort C1:
- HNSCC refractory to approved treatment (regardless of driver mutations)
• Cohort D:
- NSCLC 1L harboring EGFR sensitizing mutations (i.e. Del19, L858R)
• Cohort E:
- NSCLC osimertinib resistant (participant must have progressed on or after a previous osimertinib monotherapy)
*NOTE: Patient identification will be based on previous treatment history with TKIs, on local tests performed in CLIA-certified laboratories or on commercial diagnostics (e.g., FoundationOne). Genetic aberrations in EGFR or c-MET will be retrospectively confirmed by central testing using a validated assay in the expansion phase. For non-first line cohorts there is no limit to the number of prior treatment regimens.

4. Availability of tissue sample FFPE embedded after progression at the latest therapy (preferred in escalation, mandatory in expansion). Archival tumor tissue collected in the past may also be taken into consideration, but it is not preferred.
5. Measurable disease as defined by RECIST version 1.1 by radiologic methods (patients with non-measurable but evaluable disease can be included in the dose escalation part).
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Life expectancy = 12 weeks, as per Investigator judgment.
8. Adequate organ function, as per Investigator judgment
• Absolute neutrophil count (ANC) =1.5 X 109/L
• Hemoglobin =9 g/dL
• Platelets =100 x 109/L
• Corrected total serum calcium within normal ranges
• Serum magnesium within normal ranges (or corrected with supplements)
• Serum potassium within no

Exclusion Criteria

1. Central nervous system metastases that:
-are untreated or symptomatic (patients with untreated, asymptomatic lesions can be included if in the investigator judgment considered clinically & radiologically stable)(exp. phase only)
-require radiation or surgery(exp. phase only)
-require continued steroid therapy (> 10 mg prednisone or equivalent) to control symptoms within 14 days of study entry
2. Known leptomeningeal involvement(exp. phase only)
3. Participation in another clinical study or treatment with any investigational drug within 4 weeks prior to study entry.
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 required. Note: For agents with long half-lives, enrollment before the fifth half-life requires Sponsor approval. Cohort E patients can continue to receive osimertinib, as last treatment.
6. Major surgery or radiotherapy within 3 weeks of the first dose. Patients who received prior radiotherapy to =25% of bone marrow at any time are not eligible. Patients who received radiotherapy on lung at any time are not eligible.
7. Persistent Grade >1 clinically significant toxicities, in Investigator judgment, related to prior antineoplastic therapies (except 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 including, but not limited to:
• Prolonged QT interval > 470 msec, obtained from 3 electrocardiograms, or clinically significant cardiac arrythmia, conduction or morphology of resting ECG (ie., complete left bundle branch block, third degree heart block and second degree heart block), or electrophysiologic disease (i.e., placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate) or any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities. Patients with cardiac pacemakers who are clinically stable are eligible.
• Heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years in first-degree relatives or concomitant medication known to prolong QT interval and cause Torsades de Pointes.
• Uncontrolled (persistent) arterial hypertension: systolic blood pressure > 180 mm Hg and/or diastolic blood pressure > 100 mm Hg.
• Congestive heart failure defined as New York Heart Association class III-IV or hospitalization for CHF within 6 months of the first dose.
10. Past medical history of interstitial lung disease (ILD) or pneumonitis, or any evidence of clinically active ILD or pneumonitis.
11. History of interstitial lung disease including drug-induced interstitial lung disease, radiation pneumonitis that requires treatment with prolonged steroids or 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 malign

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified