Summary

Eligibility
for people ages 18-130 (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

Summary

Phase 2 Platform Study in Patients with Advanced Non-Small Lung Cancer who progressed on First-Line Osimertinib Therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.

Official Title

A Biomarker-directed Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Whose Disease Has Progressed on First-Line Osimertinib Therapy.

Details

This is an open-label, multicentre, multi-drug, biomarker-directed Phase 2 platform study in patients with advanced non-small cell lung cancer (NSCLC) harbouring an epidermal growth factor receptor (EGFR)-sensitizing mutation whose disease has progressed on first-line monotherapy with osimertinib.Treatment options for these patients are limited. Novel treatments for these patients are urgently required. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.

Keywords

Non-Small Cell Lung Cancer, NSCLC, tSCLC, NEC, Phase II, Platform study, Biomarker-directed, Durvalumab, Osimertinib, Savolitinib, Selumetinib, Etoposide, Gefitinib, Necitumumab, Platinum-containing doublet, Pemetrexed, EGFR positive, Carboplatin, Alectinib, Selpercatinib, Cisplatin, TKI-resistant, MET amplification, MET exon 14 skipping, EGFR, EGFR C797X, EGFR G724X, EGFR L718X, EGFR exon 20 insertion, EGFR amplification, BRAF V600E, ALK rearrangement, RET rearrangement, ROS1 rearrangement, NTRK fusion, KRAS G12C, Datopotamab deruxtecan, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Module 1: Osimertinib + Savolitinib, Module 2: Osimertinib + Gefitinib, Module 3: Osimertinib + Necitumumab, Module 4: Carboplatin + Pemetrexed + Durvalumab), Module 5: Osimertinib + Alectinib, Module 6: Osimertinib + Selpercatinib, Module 9: Osimertinib + Selumetinib, Module 10: Osimertinib + datopotamab deruxtecan

Eligibility

You can join if…

Open to people ages 18-130

applicable to all study treatment modules (Group A & B)

  1. NSCLC with the following features:
  2. Locally advanced or metastatic disease (ie, advanced NSCLC) not amenable to curative surgery or radiotherapy at study entry.
  3. 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. Any histologically identifiable component of neuroendocrine transformation to SCLC or large cell NEC is required for treatment under Module
  4. 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 anti-cancer 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

You CAN'T join if...

5).

Patients previously treated adjuvantly or neo-adjuvantly are eligible per exclusion criterion 5.

  1. 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.


Exclusion Criteria applicable to all study treatment modules (Groups A/B):

  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.

  1. Any unresolved toxicities from prior osimertinib treatment greater than CTCAE Grade 1 at the time of starting study treatment.
  2. Patients should not have discontinued osimertinib >60 days prior to the first dose of study treatment.
  3. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
  4. Absolute neutrophil count < 1.5 × 109/L.
  5. Platelet count < 100 × 109/L.
  6. Haemoglobin < 9 g/dL.
  7. Alanine transaminase (ALT) > 2.5 × ULN.
  8. Aspartate aminotransferase (AST) > 2.5 × ULN.
  9. Total bilirubin (TBL) > 1.5 × ULN, or > 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia).
  10. Creatinine clearance (CrCl) < 50 mL/min, calculated using Cockcroft-Gault equation (Cockcroft and Gault 1976) or 24-hour urine collection. For medical conditions where the Cockcroft-Gault equation is inappropriate or 24-hour urine collection is unfeasible, CrCl may be calculated differently following written approval from the Study Physician.

Locations

  • Research Site accepting new patients
    Santa Monica California 90404 United States
  • Research Site not yet accepting patients
    La Jolla California 92093 United States
  • Research Site accepting new patients
    Los Angeles California 90048 United States
  • Research Site accepting new patients
    Sacramento California 95817 United States
  • Research Site accepting new patients
    Duarte California 91010 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
AstraZeneca
Links
ORCHARD study design article. The article includes Module 5 and Module 6 but was written prior to the subsequent modules being added.
ID
NCT03944772
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 250 study participants
Last Updated