A Phase III Study to Assess the Efficacy and Safety of Almonertinib Versus Platinum-based Chemotherapy as First-line Therapy in Patients With Locally Advanced or Metastatic NSCLC Harbouring Uncommon EGFR Mutation

NCT04951648 | Unknown Phase 3

• 1 other identifier: HS-10296-305
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the efficacy and safety of Almonertinib versus platinum-based chemotherapy as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutation.

Conditions

Non-small Cell Lung Cancer

Keywords

Phase III, NSCLC, Almonertinib, uncommon EGFR mutation, first-line therapy，platinum-based chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) assessed by IRC (Independent Review Committee)

  PFS is defined as the time from randomization until the date of objective disease progression or death regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on blinded independent central review assessment according to RECIST 1.1.

  Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.

Secondary Outcomes (12)

• PFS assessed by INVs (Investigators)

  Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.

• Objective response rate (ORR) assessed by IRC

  Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.

• Duration of response (DoR) assessed by IRC

  Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.

• Disease control rate (DCR) assessed by IRC

  Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.

• Depth of response (DepOR) assessed by IRC

  Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.

Study Arms (2)

Almonertinib

EXPERIMENTAL

Drug: Almonertinib

Platinum-based doublet chemotherapy

ACTIVE COMPARATOR

Drug: chemotherapy

Interventions

Almonertinib DRUG

Almonertinib 165 mg，orally once a day Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met.

Also known as: HS-10296

Almonertinib

chemotherapy DRUG

Pemetrexed (500mg/m2) plus Carboplatin (AUC5)or Pemetrexed (500mg/m2) plus Cisplatin (75mg/m2) on Day 1 of 21day cycles (every 3 weeks) for 4\~6 cycles, followed by pemetrexed mainten-ance therapy every 3 weeks until disease progress-ssion, unacceptable toxicity or other discontinuation criteria are met.

Platinum-based doublet chemotherapy

Eligibility Criteria

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

You may qualify if:

• Subjects are willing to participate in this clinical study, understand the study procedures and are able to sign the informed consent in person.
• Age at least 18 years.
• Histologically or cytologically confirmed diagnosis of primary non-small lung cancer (NSCLC), histologically confirmed non-squamous pathology.
• Locally advanced or metastatic NSCLC.
• Patients must be treatment-naïve for locally advanced or metastatic NSCLC.
• The tumor harbors uncommon EGFR mutations (one of the following EGFR mutation: L861Q, G719X or S768I), assessed by Xiamen AmoyDx EGFR (ADx-ARMS, Super-ARMS method) kit in central laboratory.
• Measurable disease by RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Female patients should be using adequate contraceptive measures and should not be breastfeeding during the study and six months after the last dosing of study. Male patients should be willing to use barrier contraception (condoms) during the study and six months after the last dosing of study.
• A pregnancy test should be done before randomization unless having an evidence of non-child-bearing potential.

You may not qualify if:

• Treatment with any of the following:
• Prior treatment with EGFR-TKI therapy.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks prior to randomization.
• The presence of pleural effusion/peritoneal effusion/pericardial effusion requiring clinical intervention.
• Major surgery within 4 weeks prior to randomization.
• Spinal cord compression or unstable brain metastasis; Meningeal or brainstem metastases.
• Patients had received medications or herbal supplements known to be strong inducers and inhibitors of cytochrome CYP3A4 within 7 days prior to randomization or required to continue these agents during the study period.
• Patients are receiving medications known to prolong QT interval or may cause tip torsion ventricular tachycardia, or are still in the washout period (relatively random phase), or need to be continued during the study period.
• Patients were subjects in another clinical trial within 4 weeks prior to randomization or patients were within 5 half-lives of any other investigational agent.
• Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) ≥ Grade 2 from the prior anticancer therapy.
• Inadequate bone marrow reserve or organ function.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \> 470 ms obtained from 3 electrocardiograms (ECGs), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF).
• Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., PR interval \> 250 ms).
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure or any concomitant medication known to prolong the QT interval.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Sun yat-sen Univerisity Cancer Center

Guangzhou, Guangdong, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

aumolertinib; Drug Therapy

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)

Therapeutics

Central Study Contacts

Li Zhang

CONTACT

020-87342288; zhangli@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 7, 2021
• Study Start: July 15, 2021
• Primary Completion: October 4, 2023
• Study Completion: September 6, 2024
• Last Updated: July 7, 2021

Record last verified: 2021-06

Locations

CN (1)