Study in patients with Non-Small Cell Lung Cancer whose disease has got worse on Osimertinib treatment.

Phase 1

• Conditions: Advanced Non-Small Cell Lung Cancer; MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003974-29-NL
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-24
• Last Update Posted: 4 March 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 280

Inclusion Criteria

Core (Group A & B)
1. NSCLC with the following features:
(a) Locally advanced or metastatic disease (ie, advanced NSCLC) not
amenable to curative surgery or radiotherapy at study entry.
(b) Histologically or cytologically confirmed adenocarcinoma of the lung
(patients with mixed histology are eligible if adenocarcinoma is the
predominant histology) harboring EGFR mutation(s) known to be
associated with EGFR TKI sensitivity at diagnosis.
(c) Received only one line of therapy, with single-agent osimertinib, for
advanced NSCLC, with clinical benefit as judged by investigator
discretion.
(Note: a 'line' of therapy is defined as a daily anti-cancer treatment
administered for >14 days, or a single infusion of an intravenous anticancer
treatment. For instance, patients who have had <14 days of a first- or second- generation TKI prior to osimertinib, and stopped due to
adverse events, would be eligible to enter this study, see also exclusion
criteria 5).
Patients previously treated adjuvantly or neo-adjuvantly are eligible per
exclusion criterion 5.
(d) Evidence of radiological disease progression on first-line
monotherapy with osimertinib 80 mg po QD.
2. Suitable for a mandatory biopsy defined as having an accessible
tumor; by whichever modality the site uses and, ideally, confirmed by
the person who will perform the procedure; and a stable clinical
condition that will allow the patient to tolerate the procedure. The
biopsy should be performed within 60 days of the planned first dose of
study treatment.
3. Patients must have measurable disease per RECIST 1.1, as defined
by at least 1 lesion that can be accurately measured at baseline as = 10
mm at the longest diameter (except lymph nodes which must have a
short axis = 15 mm) with computed tomography (CT) or magnetic
resonance imaging (MRI), which is suitable for accurate repeated
measurements. Previously irradiated lesions or a lesion in the field of
radiation should not be used as measurable disease unless the lesion(s)
has/have demonstrated unequivocal disease progression by RECIST 1.1.
Target lesions should not be used for the baseline tumour biopsy, unless
there are no other lesions suitable for biopsy and they fulfil
requirements.
4. Adequate coagulation parameters, defined as:
International Normalisation Ratio (INR) < 1.5 × upper limit of normal
(ULN) and activated partial thromboplastin time < 1.5 × ULN unless
patients are receiving therapeutic anti-coagulation which affects these
parameters.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

Core (All modules):
1. Patients whose disease has progressed within the first 3 months of
osimertinib treatment (refractory to osimertinib treatment).
2. Patients must not have experienced a toxicity(-ies) that led to
permanent discontinuation or dose reduction of prior osimertinib.
(a) Patients who had dose reductions in the past, but were receiving a
full dose of osimertinib at the time of pre-screening should be discussed
with the Study Physician.
3. Any unresolved toxicities from prior osimertinib treatment greater
than CTCAE Grade 1 at the time of starting study treatment.
4. Patients should not have discontinued osimertinib >60 days prior to
the first dose of study treatment.
5. Inadequate bone marrow reserve or organ function as demonstrated
by any of the following laboratory values:
a) Absolute neutrophil count < 1.5 × 109/L.
b) Platelet count < 100 × 109/L.
c) Haemoglobin < 9 g/dL.
d) Alanine transaminase (ALT) > 2.5 × ULN.
e) Aspartate aminotransferase (AST) > 2.5 × ULN.
f) Total bilirubin (TBL) > 1.5 × ULN, or > 3 × ULN in the presence of
documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia).
6. Creatinine clearance (CrCl) < 50 mL/min, calculated using Cockcroft-
Gault equation (Cockcroft and Gault 1976) or 24-hour urine collection.

Study & Design

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