Osimertinib With or Without Savolitinib as 1L in de Novo MET+, EGFR+ NSCLC

NCT05163249 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: CTONG 2008
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, pilot, two-arm, randomized, multicenter study exploring the efficacy and safety of osimertinib with or without savolitinib as first-line therapy in patients with de novo MET positive, EGFR-mutant advanced NSCLC.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

non-small-cell lung cancer; Epidermal growth factor receptor; de novo MET amplification; Targeted Therapy

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective response rate (ORR) of the tumor using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

  12 weeks after the last patient enrolled

Secondary Outcomes (6)

• PFS

  18 months after the last patient enrolled

• DoR

  18 months after the last patient enrolled

• DCR

  18 months after the last patient enrolled

• percentage change from baseline in tumor size

  12 weeks after the last patient enrolled

• OS

  18 months after the last patient enrolled

Study Arms (2)

Cohort 1: osimertinib, 80mg, daily, P.O.

ACTIVE COMPARATOR

Patients will continue to receive study medication in 28 day cycles until objective disease progression, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met. Patients who progress on first-line treatment of osimertinib monotherapy will have the opportunity to receive second-line treatment of osimertinib plus savolitinib after confirmation of MET status at disease progression.

Drug: Osimertinib

Cohort 2: osimertinib 80mg daily, P.O. and savolitinib 300mg BID, P.O.

EXPERIMENTAL

All eligible patients will be randomized to receive treatment with osimertinib (80 mg daily) or osimertinib (80 mg daily) in combination with savolitinib (300 mg BID) in this study. Treatment will continue until either objective disease progression, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met. Patients in Cohort 2 can continue on savolitinib monotherapy (if osimertinib was stopped earlier) or osimertinib monotherapy (if savolitinib was stopped earlier) until objective disease progression or meet any of the discontinuation criteria.

Drug: Osimertinib; Drug: Savolitinib

Interventions

Osimertinib DRUG

osimertinib, 80mg, daily, P.O. Until objective disease progression, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criteria is met

Also known as: AZD9291

Cohort 1: osimertinib, 80mg, daily, P.O.; Cohort 2: osimertinib 80mg daily, P.O. and savolitinib 300mg BID, P.O.

Savolitinib DRUG

savolitinib 300mg BID, P.O. Until objective disease progression, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criteria is met

Also known as: HMPL-504

Cohort 2: osimertinib 80mg daily, P.O. and savolitinib 300mg BID, P.O.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Informed consent
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
• Age
• Participant must be ≥18 years at the time of signing the ICF. All genders are permitted.
• Type of Participant and Disease Characteristics
• Histologically or cytologically confirmed locally advanced or metastatic EGFRm+ NSCLC harbouring an EGFR mutation known to be associated with EGFR TKI sensitivity.
• Has not received any systemic treatment of advanced NSCLC.
• Prior adjuvant/neo-adjuvant therapy completed \> 6 months before screening is allowed.
• MET amplification/high expression as determined by FISH, IHC or NGS testing on tumor tissue collected before any systemic treatment in first line.
• MET high expression by IHC, 3+ in ≥75% of tumor cells
• increased MET gene copy number by FISH, MET gene copy ≥5 or MET / CEP7 ratio ≥2; or by tissue NGS, ≥20% tumour cells, ≥200x sequencing depth of coverage and CN ≥5.
• Local IHC, FISH and pre-existing local NGS results are acceptable, central FISH and central NGS confirmation is highly suggested if tissue sample available.
• WHO or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing and a minimum life expectancy of 12 weeks.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Medical Conditions
• As judged by the investigator, active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhoea Grade ≥2, malabsorption syndrome or previous significant bowel resection).
• Any of the following cardiac diseases currently or within the last 6 months:
• Unstable angina pectoris
• Congestive heart failure (New York Heart Association \[NYHA\] ≥Grade 2)
• Acute myocardial infarction
• Stroke or transient ischemic attack
• Uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy).
• Mean resting correct QT interval (QTcF) \>470 msec for women and \>450 msec 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 failure, electrolyte abnormalities (including: Serum/plasma potassium \< LLN; Serum/plasma magnesium \< LLN; Serum/plasma calcium \< LLN), congenital or familial long QT syndrome, family history of 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.
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECGs, eg, complete left bundle branch block, third degree heart block, second degree heart block, P-R interval \>250 msec.
• Acute coronary syndrome
• Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
• Major surgical procedures ≤28 days of beginning study drug or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead

Study Sites (1)

Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences

Guangzhou, Guangdong, 510080, China

Location

Related Publications (20)

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MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib; 1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jin-Ji Yang, MD

  Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 6, 2021
• First Posted: December 20, 2021
• Study Start: May 31, 2022
• Primary Completion: April 1, 2024
• Study Completion (Estimated): August 1, 2026
• Last Updated: February 9, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)