Savolitinib Plus Docetaxel as 2L in EGFR/ALK/ROS1/MET ex14m-wildtype NSCLC With MET Overexpression

NCT05777278 | Recruiting Phase 1

• 1 other identifier: FirstMET (ESR-22-21748)
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, pilot, single-arm, single-center study exploring the efficacy and safety of savolitinib plus docetaxel as second-line therapy in patients with MET overexpressed, EGFR/ALK/ROS1/MET ex14m-wildtype advanced NSCLC. Participants will receive treatment of docetaxel (60 mg/m2, ivgtt, q3w) in combination with savolitinib (300mg or 200mg according to safety run-in recommendation, p.o., BID) after informed consent signed. Treatment will continue until either objective disease progression, unacceptable toxicity occurs, consent is withdrawn, other discontinuation criterion is met, or study completion.

Conditions

Non-small Cell Lung Cancer

Keywords

Savolitinib; Docetaxel; MET Overexpression; Advanced NSCLC

Outcome Measures

Primary Outcomes (1)

• ORR (Objective Response Rate)

  ORR (Objective Response Rate) is defined as the proportion of participants who confirmed CR (Complete Response) or PR (Partial response) as their best overall response based on Response Evaluation Criteria in Solid Tumors (RECIST)1.1 as assessed by the investigator.

  The analysis will occur at 12 weeks after last patient in.

Secondary Outcomes (4)

• PFS (Progression-Free Survival)

  The analysis will occur when 70% data maturity of PFS events (14 PFS events) is observed in each cohort, at approximately 9 months after last patient in.

• DoR (Duration of Response)

  The analysis will occur when 70% data maturity of PFS events (14 PFS events) is observed in each cohort, at approximately 9 months after last patient in.

• DCR (Disease Control Rate)

  The analysis will occur at 12 weeks after last patient in.

• OS (Overall Survival)

  The analysis will occur when 70% data maturity of PFS events (14 PFS events) is observed in each cohort, at approximately 9 months after last subject in, up to a maximum of approximately 3 years after first subject in.

Study Arms (1)

Savolitinib Plus Docetaxel

EXPERIMENTAL

Single Arm

Drug: Savolitinib; Drug: Docetaxel

Interventions

Savolitinib DRUG

Savolitinib (300mg or 200mg according to safety run-in recommendation, p.o., BID)

Savolitinib Plus Docetaxel

Docetaxel DRUG

Docetaxel (60 mg/m2, ivgtt, q3w)

Savolitinib Plus Docetaxel

Eligibility Criteria

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

You may qualify if:

• 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.
• Female or males age ≥18 years at the time of signing the ICF.
• Histologically or cytologically confirmed locally advanced or metastatic EGFR/ALK/ROS1/MET ex14m-wildtype NSCLC.
• Has only received first line systemic treatment of non-targeted advanced NSCLC.
• Prior MET inhibitor therapy is not allowed.
• At least 28 days since last treatment.
• MET overexpression as determined IHC on tumor tissue.
• MET overexpression by IHC, 3+ in ≥50% of tumor cells
• Local IHC results are acceptable.
• 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.
• At least 1 lesion that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for accurate repeated measurements.
• Adequate haematological function defined as:
• Haemoglobin ≥9 g/dL (no transfusion in the past 2 weeks).
• Absolute neutrophil count ≥1.5×10\^9/L.

You may not qualify if:

• 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, and malabsorption syndrome).
• 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 on screening obtained from 3 electrocardiograms (ECGs) or factors that may increase the risk of QTcF prolongation such as chronic hypokalaemia not correctable with supplements, congenital or familial long QT syndrome, or 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 electrocardiograms (ECGs), e.g. complete left bundle branch block, third degree heart block, second degree heart block, PR interval \>250 msec.
• Serious underlying medical condition at the time of treatment that would impair the ability of the patient to receive protocol treatment.
• 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.
• As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including renal transplant, active bleeding diatheses or uncontrolled hypertension, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol.
• Active hepatitis B (HBV) (positive HBV surface antigen \[HBsAg\] result) or hepatitis C (HCV). Patients with a past or resolved HBV or HCV infection are eligible if:
• Negative for HBsAg and positive for hepatitis B core antibody \[anti-HBc\] or

Sponsors & Collaborators

• The First Affiliated Hospital of Guangzhou Medical University: lead

Study Sites (1)

Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

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; Docetaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Jianxing He, M.D

  The First Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianxing He, M.D

CONTACT

+86-20-83337792; drjianxing.he@gmail.com

Wenhua Liang, M.D

CONTACT

+86-13710249454; liangwh1987@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Clinical trials with a single arm

Study Record Dates

• First Submitted: February 21, 2023
• First Posted: March 21, 2023
• Study Start: July 26, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

CN (1)