Osimertinib plus savolitinib in patients with EGFRm+/MET+ non small cell lung cancer following prior osimertinib

Phase 1

• Conditions: EGFRm+ and MET+, Locally Advanced or Metastatic 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: EUCTR2018-003012-51-IT
• Lead Sponsor: ASTRAZENECA AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-15
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 259

Inclusion Criteria

-Pts must be=18 years of age(=20 years of age in Japan).All genders are permitted.
-Histologically or cytologically confirmed locally advanced or metastatic EGFRm+ NSCLC harbouring an EGFR mutation known to be associated with EGFR TKI sensitivity and permitted in the osimertinib national label(such as either exon 19 deletion and/or L858R)which is not amenable to curative therapy.
-Documented radiologic disease progression:
a)For savolitinib 300mgOD(or 600mgOD if enrolled prior to CSPv5.0)incombination with osimertinib 80mgOD:documented radiologic disease progression following trt with osimertinib(osimertinib doesn't need to bethe mostrecent therapy).
b)For savolitinib 300mgBID or 600mgOD in combination withosimertinib 80mgOD:Documented radiologic disease progression following trt with1L or2L osimertinib(osimertinib must bethe most recent anti-cancer therapy).
-METamplification/highexpression asdetermined by FISH(central),IHC(central) or NGS(pre-existing)testing on tumour tissue collected following progression on prior osimertinib trt.
-Available tumour sample for centralMET FISH and IHC analysis or willingness to collect additional tissue for centrl testing which fulfils the following requirements:Obtained following progression on previous osimertinib therapy;obtained within 2years of submission for METanalysis;sufficient tissue to meet the min tissue requirement defined in the current LabManual.
-At least 1lesion,not prvsly irradiated,not biopsied during the screening,that can be accurately measured at baseline as>10mm in the longest diameter(except lymphnodes which must have short axis>15 mm)with CT orMRI which is suitable for accurate repeated measurements.If only 1measurable lesion exists,it's acceptable to be used as long as baseline tumour assessment scans are done at least 14dys after the screening tumor smple collection is performed.
-Prior lines of therapy in locally advanced/metastatic setting:
a)Forsavolitinib300mgOD(and600mgOD if enrolled prior to CSP v5.0) in combination with osimertinib 80mgOD: Pts must have received at least 1but no more than3 prior lines of therapy(including investigational one).No more than 1prior line of chemoth regimen is acceptable.A chemoth regimen including a (PD1) or a PD1 ligand 1(PD L1) agent is acceptable,provided it was not the most recent line of therapy. No more than 2 prior lines oftherapy containing EGFR-TKI are acceptable.
b)Forsavolitinib 300mgBID or600mgOD incombination with osimertinib 80mgOD:Patients will receive1or2 prior lines of therapy(see inclusioncriterion5).Nochemotherapy/immunotherapy is allowed.
-Adequate haematological function defined as: Absolute neutrophil count =1500/µL; Haemoglobin =9 g/dL (no transfusion in the past 2weeks);Platelets=100,000/µL(no transfusion in the past 10 days)
-Adequate liver function(ALT,AST=2.5 x ULN with total bilirubin=ULN OR Total bilirubin >ULN to=1.5x ULN withALT and AST=ULN)
-Adequate renal function -creatinine<1.5 times the institutional ULN OR a glomerular filtration rate=50 mL/min.Confirmation of creatinineclearance is only required when creatinine is>1.5 times ULN.
-Adequate coagulation parameters- INR <1.5 x ULN and activated partial thromboplastin time <1.5 x ULN unless patients are receiving therapeutic anti coagulation whichaffects these parameters.
-Patients with known tumour thrombus ordeep vein thrombosis are eligible if clinically stable on low molecular weight heparin for =2 weeks.
- ECOG/WHO erformance status of 0or1 with node

Exclusion Criteria

-Unres toxicit from prior therapy CTCAE >1 at time of starting study treatment with exception of alopecia and Gr2 prior platinum ther related neuropat judged by invest, active gastroint dis or other condit that will interfere signif with ADME of oral ther. (eg, ulcer disease, uncontr nausea, vomiting, diarrhoea Gr>=2, malabsorpt syndr or prev signifi bowel resection)
- Any of the follow cardiac dis current or within last6moths: Unstab angina pectoris; Congest heart failure ([NYHA>=Gr2); Acute myocard infarction;Stroke or transient ischemic attack; Uncontr hypert (BP=150/95mmHg despite medical therapy);Mean resting correct QT int (QTcF)>470msec for women and>450msec for men at Screening, obtained from 3 ECGs using the screening clinic ECG machine derived QTcF value. (Any factors that may increase the risk of QTcF prolongation or risk of arrhythmic events such as heart fail, chronic hypokalaemia not correctable with suppl, congenital or famil long QT syndr, family history of unexpl sudden death under 40 years of age in first-degree relatives or any concomit medic known to prolongQT interval and cause Torsade de Pointes. Any clinically imp abnormal in rhythm, conduction or morphol of resting ECGs, eg, complete left bundle branch block, third degree heart block, second degree; Acute coromnary Syndrome)
- Wide field radiother (incl therap radioisotopes such as strontium89) admin=<28days or limited field radiation for palliation<=7days prior to starting study drug or has not recovered from side effects of such therapy
- Major surgic proced<=28days of beginning study drug or minor surg proced<=7days
- Evid. Of severe or uncontr syst diseases, incl renal transpl, active bleeding diatheses or uncontr hypert which in invest's opinion makes it undesirable for the pt to particip
- Active hepatitis BorC or known serious active infection e.g. tubercul or HIV. Viral testing not required for assessment of elegibility for study
- Presence of other active cancers,or history of treatment for invas cancer, within last 5 years.Pts with Stage I cancer who have received definitive local treatment at least 3years previously, and are considered unlikely to recur are eligible. All pts with previously treated in situ carcinoma (ie,non-invasive)are eligible, as are pts with history of non-melanoma skin cancer
- Spinal cord compression or brain metast unless asymptom,stable and not requiring steroids for at least 2 weeks prior to start of study treatm
- Past medical history of interstitial lung disease(ILD),drug-induced ILD,radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
- Prior or current treatment with a 3rd generation EGFR-TKI other than osimertinib.
- Prior or current treatm with savolitinib or another MET inhib (eg, foretinib, crizotinib, cabozantinib, onartuzumab, capmatinib)
- Pts who received>=4lines of systemic therapy for NSCLC
- Any cytotoxic chemoth., investig agents or other anticancer drugs for treatment of adv NSCLC from a prev treat regimen or clinical study within14days prior to first dose of study treatment with exception of monoth osimertinib which may continue uninterrupt during screening
-Pts currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4, strong inhibitors of CYP1A2 within 2 weeks of the first dose of study treatment (3 weeks for St John's Wort).
- Particip in another clin s

Study & Design

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