A Phase III Study to Assess the Effects of Almonertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer

NCT04951635 | Recruiting Phase 3

• 1 other identifier: HS-10296-304
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the efficacy and safety of Almonertinib versus placebo following chemoradiation in patients with stage III unresectable epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC).

Conditions

Non-small Cell Lung Cancer

Keywords

Phase III, stage III NSCLC, unresectable NSCLC, Almonertinib, Maintenance Therapy, EGFR, chemoradiation therapy

Outcome Measures

Primary Outcomes (1)

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

  Progression-free survival (PFS) assessed by IRC (Independent Review Committee) Description: PFS is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) 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 ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.

Secondary Outcomes (8)

• PFS assessed by INVs (Investigators)

  Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.

• Time to CNS PFS assessed by IRC

  Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.

• Overall survival (OS)

  From baseline until death due to any cause; up to a maximum of approximately 4 years.

• Objective response rate (ORR)

  Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years.

• Duration of response (DoR)

  Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years.

Study Arms (2)

Almonertinib

EXPERIMENTAL

Drug: Almonertinib

Placebo Almonertinib

PLACEBO COMPARATOR

Drug: Placebo Almonertinib

Interventions

Almonertinib DRUG

The initial dose of Almonertinib 110 mg daily can be reduced to 55 mg daily under specific conditions. Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met. The 2:1 ratio (Almonertinib to placebo).

Also known as: HS-10296

Almonertinib

Placebo Almonertinib DRUG

The initial dose of Placebo Almonertinib 110 mg daily can be reduced to 55 mg daily under specific conditions. Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met. The 2:1 ratio (Almonertinib to placebo).

Placebo Almonertinib

Eligibility Criteria

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

You may qualify if:

• Provision of informed consent before any study-specific procedures, sampling and analyses.
• Male or female, age at least 18 years.
• Histologically or cytologically confirmed diagnosis of primary non-small lung cancer (NSCLC) on predominantly non-squamous pathology who present with locally advanced, unresectable (Stage III) disease (according to AJCC 8th edition lung cancer classification). Recommended by not required: In addition to obvious cT4 disease, lymph node status N2 or N3 should be confirmed by intrabronchial ultrasound, mediastinoscopy or thoracoscopy biopsy, and under the condition of no biopsy or negative biopsy, the whole body screening of 18F-Fluro-deoxyglucose positron emission tomography (PET)or contrast agent-enhanced computed tomography (CT) to confirm.
• The tumor harbours one of the two common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19Del, L858R), either alone or in combination with other EGFR mutations including T790M, assessed by cobas® EGFR Mutation Test (Roche Diagnostics) or Xiamen AmoyDx EGFR (ADx-ARMS, Super-ARMS method) kit in site or central laboratory.
• Patients must have received either concurrent chemoradiation or sequential chemoradiation including at least 2 cycles of platinum based chemotherapy and a total dose of radiation of 60 Gy ±10% (54 to 66 Gy).
• Chemoradiation must be completed ≤6 weeks prior to randomization.
• Patients must not have had disease progression during or following definitive platinum-based, chemoradiation therapy.
• A WHO performance status of 0-1 with no deterioration over the past 2 weeks and a minimum life expectancy of 12 weeks.
• Female patients should be using adequate contraceptive measures and should not be breastfeeding at the screening period, during the study, and six months after the last dosing of study. A pregnancy test should be done before first dosing unless having evidence of non-child-bearing potential.
• Male patients should be willing to use barrier contraception (condoms)

You may not qualify if:

• Treatment with any of the following:
• Prior treatment with any prior chemotherapy, radiation therapy, immunotherapy or investigational agents for NSCLC outside of that received in the definitive setting for Stage III disease (chemotherapy and radiotherapy in SCRT and CCRT regimens is allowed for treatment of Stage III disease). Patients who have previously undergone surgery for stage I or stage II NSCLC can be enrolled. If neoadjuvant or adjuvant therapy (non-EGFR tyrosine kinase inhibitor) is used, neoadjuvant or adjuvant therapy needs to be completed for at least half a year (6 months) before enrollment.
• Prior treatment with EGFR-TKI therapy.
• Major surgery (including primary tumor surgery, excluding placement of vascular access) within 4 weeks of the first dose of study drug.
• Patients currently receiving (unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers and inhibitors of cytochrome CYP3A4 (at least 7 days prior to receiving the first dose of study drug).
• Treatment with an investigational drug within five half-lives of the compound or any of its related material.
• Mixed small cell and non-small cell lung cancer histology.
• History of interstitial lung disease (ILD) prior to chemoradiation.
• Symptomatic pneumonitis following chemoradiation.
• Inadequate bone marrow reserve or organ function.
• Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) ≥ Grade 2 from the prior chemoradiation therapy.
• 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)

Shandong Cancer Hospital

Ji'nan, Shandong, 250117, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

aumolertinib

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• 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: March 18, 2021
• Primary Completion: July 15, 2024
• Study Completion (Estimated): January 15, 2027
• Last Updated: June 16, 2022

Record last verified: 2022-06

Locations

CN (1)