A Phase 2 interventional study of Osimertinib and Savolitinib in Non-Small Cell Lung Cancer, sponsored by AstraZeneca. Active, not recruiting at 47 sites in 9 countries. Open to participants aged 18 Years to 130 Years. Per ClinicalTrials.gov, last updated 2025-01-30.
Sponsored by AstraZeneca · Phase 2, Interventional, and Treatment
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.
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.
7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.
This study's enrollment of 247 is above the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.
Browse Lung Neoplasms studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion criteria applicable to all study treatment modules (Group A \& B)
NSCLC with the following features:
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 exclusion criteria 5).
Patients previously treated adjuvantly or neo-adjuvantly are eligible per exclusion criterion 5.
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.
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Exclusion Criteria applicable to all study treatment modules (Groups A/B):
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.
Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
The patients in this group will receive osimertinib taken in combination with savolitinib
Drug: Osimertinib · Drug: Savolitinib
The patients in this group will receive osimertinib taken in combination with gefitinib
Drug: Osimertinib · Drug: Gefitinib
The patients in this group will receive osimertinib taken in combination with necitumumab
Drug: Osimertinib · Drug: Necitumumab
The patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab.
Drug: Durvalumab · Drug: Carboplatin · Drug: Pemetrexed
Patients in this group will not receive study treatment but receive further anticancer care (Standard of Care therapy or other experimental therapies) or supportive care, as clinically indicated, in accordance with local practice. With Group C, the aim is to understand the clinical course and/or outcome for the overall clinical population after progression on first-line monotherapy with osimertinib.
The patients in this group will receive osimertinib taken in combination with alectinib
Drug: Osimertinib · Drug: Alectinib
The patients in this group will receive osimertinib taken in combination with selpercatinib
Drug: Osimertinib · Drug: Selpercatinib
The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab.
Drug: Durvalumab · Drug: Carboplatin · Drug: Etoposide · Drug: Cisplatin
The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin).
Drug: Osimertinib · Drug: Carboplatin · Drug: Pemetrexed · Drug: Cisplatin
The patients in this group will receive osimertinib taken in combination with selumetinib
Drug: Osimertinib · Drug: Selumetinib
The patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan.
Drug: Osimertinib · Drug: Datopotamab deruxtecan
Osimertinib given orally at 80 mg once daily
Also known as: TAGRISSO
Savolitinib will be given orally at 300 mg or 600mg once daily
Gefitinib given orally at 250 mg once daily
Also known as: Iressa
Necitumumab given IV at 800 mg on Day 1 and Day 8 of every 3-week cycle
Also known as: Portrazza
Durvalumab given IV at 1500 mg on Day 1 of every cycle
Also known as: IMFINZI
Carboplatin given IV on Day 1 of every 21-day cycle for up to 6 cycles
Pemetrexed given IV at 500 mg/m2 body BSA on Day 1 of every cycle
Alectinib given orally at 600mg twice daily and for Japanese patients at 300mg twice daily.
Also known as: Alecensa
Selpercatinib given orally at 160mg twice daily
Also known as: Loxo-292, Retevmo, Retsevmo
Selumetinib given orally at 75 mg twice daily for 4 days, followed by 3 days off treatment
Also known as: Koselugo
Etoposide 80-100 mg/m2 given IV on day 1, 2 and 3 of every 21-day cycle for up to 4 cycles.
Cisplatin 75-80 mg/m2 given IV on days 1 of each cycle
Datopotamab deruxtecan given IV at 4 or 6 mg/kg on Day 1 of every 3-week cycle.
Also known as: DS 1062a
Objective response rate (ORR)
The percentage of patients with a confirmed investigator-assessed complete or partial response according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).
Time frame: Measured from first dose until confirmed response or progression. For each patient this is expected to be 3 months on average
Progression-free survival (PFS)
The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression). Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST (Response Evaluation Criteria In Solid Tumours)1.1 defined disease progression or cessation of study treatment (if treating beyond progression).
Time frame: Measured from first dose until progression. For each patient this is expected to be 6 months on average
Duration of response (DoR)
The time from the date of first response until date of disease progression or death in the absence of disease progression. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).
Time frame: Measured from response until progression. For each patient this is expected to be 6 months on average
Overall survival (OS)
The time from the date of the first dose of study treatment until death due to any cause.
Time frame: Measured from first dose until death or final cohort data cut-off. For each patient this is expected to be 20 months on average
Plasma/serum concentrations of therapeutic agents
Blood samples will be collected at various timepoints to evaluate the sparse pharmacokinetics of study therapeutic agents.
Time frame: Pre-dose and 1 hour post-dose blood samples on Day 1 of Cycles 1, 3 (Cycle 2 for durvalumab), 6 for all therapeutic agents and a sample at the 90-day safety follow up for durvalumab only. (One Cycle = 21 or 28 days, depending on treatment).
Plasma/serum concentrations of therapeutic agents
Blood samples will be collected at various timepoints to evaluate the serial pharmacokinetics of study therapeutic agents
Time frame: Pre-dose and serial post-dose blood samples (1 hour, 2 hours, 4 hours, 6 hours, 8 hours) on Day 15 of Cycle 1 for alectinib and selpercatinib only.
Incidence of Treatment-emergent adverse events (AEs) and serious adverse events (SAEs) as characterized and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v5
To evaluate safety and tolerability of each study treatment
Time frame: Continuously from first dose to end of safety follow up after study treatment discontinuation (approximately up to 21 Months)
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting information: Study protocol, Sap
This study is active, not recruiting, as verified in Dec 2024. You cannot join it, but the record below documents what was studied.
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