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JOURNAL ONKOLOGIE – STUDIE

A Phase 1/2 Study Evaluating MCLA-129, a Human Anti-EGFR and Anti-c-MET Bispecific Antibody, in Patients With Advanced NSCLC and Other Solid Tumors

Rekrutierend

NCT-Nummer:
NCT04868877

Studienbeginn:
April 2021

Letztes Update:
09.05.2023

Wirkstoff:
MCLA-129, Osimertinib

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Squamous Cell, Squamous Cell Carcinoma of Head and Neck, Esophageal Squamous Cell Carcinoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Merus N.V.

Collaborator:
-

Kontakt

Studienlocations
(3 von 53)

The Catholic University of Korea, St. Vincent's Hospital
16247 Suwon, Gyeonggi-do
Korea, Republic ofNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Byoung-Yong Shim, MD, PhD.
Phone: +82-31-249-8016» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Brief Summary:

A phase 1/2 open-label multicenter study will be performed with an initial dose escalation

part to determine the MTD and/or the RP2D of MCLA-129 as monotherapy in patients with NSCLC,

HNSCC, GC/GEJ, ESCC, or other solid tumors and who have progressed after receiving prior

therapy for advanced/metastatic disease.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Histologically or cytologically confirmed solid tumors with evidence of metastatic or

locally advanced unresected disease that is incurable.

- Patients with NSCLC, GC/GEJ, HNSCC, or ESCC 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.

- Part Two: Patients with NSCLC, HNSCC, other solid tumors and applicable mutations as

determined by the investigator

- Availability of archival or a fresh tumor tissue sample.

- Measurable disease as defined by RECIST version 1.1 by radiologic methods.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Life expectancy ≥ 12 weeks, as per Investigator.

- Adequate organ function:

- Absolute neutrophil count (ANC) ≥1.5 X 10^9/L

- Hemoglobin ≥9 g/dL

- Platelets ≥100 x 10^9/L

- Corrected total serum calcium within normal ranges

- Serum magnesium within normal ranges (or corrected with supplements)

- Serum potassium within normal ranges

- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3 x upper limit

of normal (ULN) and total bilirubin ≤1.5 x ULN (patients with Gilbert's syndrome

are eligible if conjugated bilirubin value is within normal limits); in cases of

liver involvement, ALT/AST ≤5 x ULN and total bilirubin ≤2 x ULN will be allowed

- Serum creatinine ≤1.5 x ULN or creatinine clearance ≥50 mL/min calculated

according to the Cockcroft and Gault formula or MDRD formula for patients aged

>65 years

- Serum albumin >3.3 g/dL

Exclusion Criteria:

- 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.

- Known leptomeningeal involvement.

- Participation in another clinical study or treatment with any investigational drug

within 4 weeks prior to study entry.

- 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.

- 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.

- 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.

- History of hypersensitivity reaction or any toxicity attributed to human proteins or

any of the excipients that warranted permanent cessation of these agents.

- History of clinically significant cardiovascular disease including, but not limited

to:

- Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to

first dose of study drug, or any of the following within 6 months prior to the

first dose of study drug: myocardial infarction, unstable angina, stroke,

transient ischemic attack, coronary/peripheral artery bypass graft, or any acute

coronary syndrome.

- Prolonged QT interval > 480 msec or clinically significant cardiac arrythmia 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 of age in first-degree relatives or

any concomitant medication known to prolong the 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 (CHF) defined as New York Heart Association (NYHA) class

III-IV or hospitalization for CHF within 6 months of the first dose of study

drug.

- Clinically significant pericardial effusion.

- Myocarditis.

- 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.

- 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.

- Current serious illness or medical conditions including, but not limited to

uncontrolled active infection, clinically significant pulmonary, metabolic or

psychiatric disorders

- Active Hepatitis B infection (HBsAg positive) without receiving antiviral treatment.

- Positive test for Hepatitis C ribonucleic acid (HCV RNA);

- Known history of HIV (HIV 1/2 antibodies).

Studien-Rationale

Primary outcome:

1. To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of single agent MCLA-129 in patients with NSCLC, GC/GEJ adenocarcinoma, HNSCC or ESCC, with disease progression after prior therapy for advanced/metastatic disease. (Time Frame - First 28 days of treatment)

2. To evaluate the ORR of MCLA-129 alone or in combination with Osimertinib in molecularly defined populations of advanced/metastatic solid tumors. (Time Frame - From first dose until 1 year after end of treatment or initiation of an alternative treatment, whichever occurs first.)

Secondary outcome:

1. To evaluate preliminary antitumor activity in terms of best overall response (BOR) (Time Frame - Every 8 weeks until study ends, approximately 2 years)

2. To evaluate preliminary antitumor activity in terms of overall response rate (ORR) (Time Frame - Every 8 weeks until study ends, approximately 2 years)

3. To evaluate preliminary antitumor activity in terms of disease control rate (DCR) (Time Frame - Every 8 weeks until study ends, approximately 2 years)

4. To evaluate preliminary antitumor activity in terms of duration of response (DoR). (Time Frame - Every 8 weeks until study ends, approximately 2 years)

5. To evaluate progression-free survival (PFS) (Time Frame - Every 8 weeks until study ends, approximately 2 years)

6. To evaluate overall survival (OS). (Time Frame - Every 8 weeks until study ends, approximately 2 years)

7. Maximum plasma concentration [Cmax] (Time Frame - 12 months)

8. Plasma concentration at 0 hours [C0h] (Time Frame - 12 months)

9. Area under the concentration versus time curve from time zero to time t [AUC0-t] (Time Frame - 12 months)

10. Area under the concentration versus time curve [AUC0-∞] (Time Frame - 12 months)

11. Time to reach maximum concentration [tmax] (Time Frame - 12 months)

12. Half-life [t1/2] (Time Frame - 12 months)

13. To assess changes in cytokines (TNFα) in serum blood following administration of MCLA-129 (Time Frame - 12 months)

14. To assess changes in cytokines (IFNγ) in serum blood following administration of MCLA-129 (Time Frame - 12 months)

15. To assess changes in cytokines (IL-1β) in serum blood following administration of MCLA-129 (Time Frame - 12 months)

16. To assess changes in cytokines (IL-2) in serum blood following administration of MCLA-129 (Time Frame - 12 months)

17. To assess changes in cytokines (IL-6) in serum blood following administration of MCLA-129 (Time Frame - 12 months)

18. Incidence of anti-drug antibodies in serum blood against MCLA-129 (Time Frame - 12 months)

19. Serum titers of anti-drug (MCLA-129) antibodies in serum blood (Time Frame - 12 months)

20. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 (Time Frame - 12 months)

21. Proportion of patient with treatment discontinuations (Time Frame - 12 months)

Studien-Arme

  • Experimental: Part 2 NSCLC harboring EGFR exon 20 Insertion
    Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
  • Experimental: Part 2 NSCLC harboring cMet exon 14 skipping mutation
    Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
  • Experimental: Part 2 Select solid tumors harboring an EGFR or cMet driving mutation
    Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
  • Experimental: Part 2 NSCLC First-line
    Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and Osimertinib orally once daily starting at a dose of 80mg.
  • Experimental: Part 2 NSCLC Second-line or more
    Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and Osimertinib orally once daily starting at a dose of 80mg.

Geprüfte Regime

  • MCLA-129 (bispecific):
    full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET
  • Osimertinib (Tagrisso):
    Approved, 3rd-generation EGFR-TKI

Quelle: ClinicalTrials.gov


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