Non-small Cell Lung CancerPhase 3NCT04951635
A Phase III Study to Assess the Effects of Almonertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer
A Phase 3 study testing Almonertinib in people with Non-small Cell Lung Cancer, run by Jiangsu Hansoh Pharmaceutical Co., Ltd. at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Almonertinib
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteChina
- Study dates
- 18 Mar 2021to 15 Jan 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
Who cannot join
- 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.
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- 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.
- Left ventricular ejection fraction (LVEF) ≤ 40%.
- History of other malignancies, excluding fully treated non-melanoma skin cancer, in-situ cancer, or other solid tumors that hadn't recurrent for > 5 years following the end of treatment.
- Any evidence of severe or uncontrolled systemic diseases (including uncontrolled hypertension and active bleeding diatheses) or active infection (including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV)).
- Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow the study drug that would preclude adequate absorption of Almonertinib.
- History of hypersensitivity to any active or inactive ingredient of Almonertinib or to drugs with a similar chemical structure or class to Almonertinib.
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
- Any severe and uncontrolled ocular disease that may, in the ophthalmologist's opinion, present a specific risk to the patient's safety.
- Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shandong Cancer Hospital
Ji'nan, Shandong, 250117
Jinming Yu, +86-0531-67626929, sdzlllh803@126.com
About this study
Official title: A Phase III, Randomised, Double-blind, Placebo-controlled, Multi-centre Study of Almonertinib as Maintenance Therapy in Patients With Locally Advanced, Unresectable EGFR Mutation-positive Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based Chemoradiation Therapy
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).
Read the detailed description
This is a randomized, double-blind, placebo-controlled, multicenter, phase III study to assess the efficacy and safety of Almonertinib following chemoradiation in patients with stage III unresectable EGFRm+ NSCLC, including the most common EGFR sensitizing mutations (Ex19Del and L858R), either alone or in combination with other EGFR mutations (e.g., T790M). Chemoradiation may have been given either concurrently or sequentially. Patients whose disease has not progressed following chemoradiation will be randomised within 6 weeks of completion of chemoradiation to receive Almonertinib or placebo in a 2:1 ratio, and treatment will be continued until disease progression, unacceptable toxicity or other discontinuation criteria are met. After progression, patients can be unblinded and may receive open-label Almonertinib for as long as their treating physician considers they are deriving clinical benefit.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Almonertinib, Placebo Almonertinib
- Keywords
- Phase III, stage III NSCLC, unresectable NSCLC, Almonertinib, Maintenance Therapy, EGFR, chemoradiation therapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlmonertinibDrug
Also called HS-10296
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).
Placebo AlmonertinibDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Almonertinib | Experimental | Not described Receives: Drug: Almonertinib |
| Placebo Almonertinib | Placebo comparator | Not described Receives: Drug: Placebo Almonertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
PFS is defined as the time from randomization to progression of tumor as assessed by INVs or death from any cause on study.
Measured: 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
Defined as earlier event of CNS progression or death based on blinded independent central review assessment according to RECIST 1.1.
Measured: 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)
OS is defined as the time from the date of randomization until death due to any cause.
Measured: From baseline until death due to any cause; up to a maximum of approximately 4 years.
Objective response rate (ORR)
Defined as the number (%) of patients with measurable disease with at least 1 visit response of CR (Complete response) or PR (Partial response) based on blinded independent central review assessment according to RECIST 1.1.
Measured: 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)
Defined as the time from the date of first documented response (i.e., subsequently confirmed) until the date of documented progression or death in the absence of disease progression based on blinded independent central review assessment according to RECIST 1.1.
Measured: 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.
Disease control rate (DCR)
Defined as Disease control rate is defined as the percentage of subjects who have a best overall response of CR or PR or SD based on blinded independent central review assessment according to RECIST 1.1.
Measured: 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.
Time to death or distant metastases (TTDM)
Defined as the time from the date of randomization until the first date of distant metastasis or date of death in the absence of distant metastasis based on blinded independent central review assessment according to RECIST 1.1
Measured: 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.
Incidence of Adverse Events (AEs)
AEs are graded according to CTCAE v5.0 and recorded in the case report form.
Measured: From the screening period to 28 days after treatment completion, approximately 4 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2021
- Study start18 Mar 2021
- Primary completion15 Jul 2024 (estimated)
- Study completion15 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Jiangsu Hansoh Pharmaceutical Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04951635
- Sponsor's protocol ID
- HS-10296-304
- Status last verified
- Jun 2022
- First submitted
- 30 Jun 2021
- Last updated
- 16 Jun 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomised, Double-blind, Placebo-controlled, Multi-centre Study of Almonertinib as Maintenance Therapy in Patients With Locally Advanced, Unresectable EGFR Mutation-positive Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based Chemoradiation Therapy
- ClinicalTrials.gov ID
- NCT04951635
- Acronym / sponsor ID
- HS-10296-304
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- Phase III, stage III NSCLC, unresectable NSCLC, Almonertinib, Maintenance Therapy, EGFR, chemoradiation therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 18 Mar 2021 (actual)
- Primary completion
- 15 Jul 2024 (estimated)
- Study completion
- 15 Jan 2027 (estimated)
- First posted
- 7 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This is a randomized, double-blind, placebo-controlled, multicenter, phase III study to assess the efficacy and safety of Almonertinib following chemoradiation in patients with stage III unresectable EGFRm+ NSCLC, including the most common EGFR sensitizing mutations (Ex19Del and L858R), either alone or in combination with other EGFR mutations (e.g., T790M). Chemoradiation may have been given either concurrently or sequentially. Patients whose disease has not progressed following chemoradiation will be randomised within 6 weeks of completion of chemoradiation to receive Almonertinib or placebo in a 2:1 ratio, and treatment will be continued until disease progression, unacceptable toxicity or other discontinuation criteria are met. After progression, patients can be unblinded and may receive open-label Almonertinib for as long as their treating physician considers they are deriving clinical benefit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Almonertinib | Experimental | Drug: Almonertinib |
| Placebo Almonertinib | Placebo comparator | Drug: Placebo Almonertinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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).
Key exclusion criteria (23 listed)
- Treatment with any of the following:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlmonertinibAlso: HS-10296The 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). | Drug | Almonertinib |
| Placebo AlmonertinibThe 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). | Drug | Placebo Almonertinib |
Primary outcome
Progression-free survival (PFS) assessed by IRC (Independent Review Committee)
Time frame: 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.
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.
8 secondary outcomes
PFS assessed by INVs (Investigators)
Time frame: 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
Time frame: 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)
Time frame: From baseline until death due to any cause; up to a maximum of approximately 4 years.
Objective response rate (ORR)
Time frame: 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)
Time frame: 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.
Disease control rate (DCR)
Time frame: 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.
Time to death or distant metastases (TTDM)
Time frame: 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.
Incidence of Adverse Events (AEs)
Time frame: From the screening period to 28 days after treatment completion, approximately 4 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Almonertinib in people with Non-small Cell Lung Cancer, run by Jiangsu Hansoh Pharmaceutical Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) assessed by IRC (Independent Review Committee) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2022.