Advanced non-small cell lung cancer
Conditions
Interventions
Cohort 1:Capivasertib: 320 mg, to be administered twice daily from day 1 to 4 of a 7-day cycle
Osimertinib: 80 mg, to be administered once daily continuously
till disease progression (PD) or unaccepta
Cohort 2:Capivasertib: 400 mg, to be administered twice daily from day 1 to 4 of a 7-day cycle
Osimertinib: 80 mg, to be administered once daily continuously
till disease progression (PD) or unaccepta
Dose Expansion Cohort:Capivasertib: RPD2, to be administered twice daily from day 1 to 4 of a 7-day cycle
Osimertinib: 80 mg, to be administered once daily continuously
till disease progression (PD) o
Sponsors
Cancer Hospital of Shanxi Province
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Informed consent 1. Provision of signed and dated, written informed consent form (ICF) prior to any mandatory and non-mandatory study-specific procedures, sampling and analyses; Age 2. Male or female age >=18 years at the time of signing the ICF; Type of participant and disease characteristics; 3. Histologically or cytologically confirmed non-squamous locally advanced or metastatic NSCLC which is not amenable to curative therapy; 4. Documented EGFR sensitive mutations (exon19 deletion, L858R mutation) prior to the first-line EGFR-TKI therapy; 5. Documented radiologic progression on first-line treatment with Osimertinib monotherapy or Osimertinib plus chemotherapy: • Participants treated with Osimertinib in the adjuvant setting can be included if progression occurred = 10 mm in the longest diameter (except lymph nodes which must have short axis = 15 mm) with CT or MRI, which is suitable for accurate repeated measurements. If only one measurable lesion exists, it is acceptable to be used if baseline tumour assessment scans are done at least 14 days after the screening tumour specimen collection is performed; 8. Adequate bone marrow reserve and organ function as follows: • Absolute neutrophils count (ANC) >=1.5x10^9/L. • Platelets count >=100x10^9/L. • Haemoglobin (Hb) >=90g/L. • Total bilirubin =50mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN. 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 10. Patients with hepatitis B virus (HBV) are only eligible for inclusion if they meet all the following criteria: • Demonstrated absence of hepatitis C virus (HCV) co-infection or history of HCV co-infection; • Demonstrated absence of human immunodeficiency virus (HIV) infection; • Participants with active HBV infection are eligible if they are: • Receiving a
Exclusion criteria
Exclusion criteria: Medical conditions 1. Patients harbouring concurrent actionable driver mutations with locally approved targeted therapies (e.g., MET amplification) will be excluded; 2. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD; 3. Clinically significant abnormalities of glucose metabolism as defined by any of the following: • Fasting glucose >=7.0 mmol/L (126 mg/dL) or 2 hours after glucose solution intake, blood glucose >=11.1 mmol/L (200 mg/dL). • HbA1c >=8.0% (63.9 mmol/mol) at screening; Note: for any patient with evidence of impaired glucose control or insulin resistance refer to the Capivasertib Toxicity Management Guidelines. 4. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection (e.g. patients receiving treatment for infection) including hepatitis C and human immunodeficiency virus (HIV), or active uncontrolled hepatitis B virus (HBV) infection, or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice); • Screening for chronic conditions is not required; 5. Spinal cord compression, leptomeningeal metastasis, or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention; 6. Any of the following cardiac criteria: • Mean resting corrected QTc >470 msec, obtained from triplicate electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value; • History of QT prolongation associated with other medications that required discontinuation of that medication; • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block and second-degree heart block. • Medical history significant for arrhythmia (e.g., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted to enter the study based on the Investigator judgement with cardiologist consultation recommended. • Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including: - Hypokalaemia|* >= CTCAE Grade 2. 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 Torsade de Pointes. * Correction of electrolyte abnormalities should be documented prior to first dose. • Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Associatio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Number of Dose-limiting toxicities (DLTs);Part A: Adverse events (AEs)/serious adverse events (SAEs) (graded by CTCAE Version 5.0);Part A: RCD;Part B: Confirmed ORR assessed by the Investigator per RECIST 1.1 criteria; | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A: Confirmed ORR assessed by the Investigator per RECIST 1.1 criteria;Part B: PFS, DoR, DCR, Percentage change from baseline in tumor size by Investigator assessment;Part B: OS;Part B: AE/SAE, ADR, AESI; | — |
Countries
China
Contacts
Public ContactJie Wang
Cancer Hospital of Shanxi Province
Outcome results
None listed