Non Small Cell Lung CancerPhase 3ACROSS1NCT04500704

Almonertinib Plus Chemotherapy as First-line Treatment in Patients With EGFR Concomitant Non-EGFR Driver Gene Mutant, Locally Advanced or Metastatic NSCLC

A Phase 3 study testing Almonertinib and Almonertinib plus carboplatin and pemetrexed in people with Non Small Cell Lung Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 6 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

This is a multicenter, randomized, controlled, phase III study. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Non Small Cell Lung Cancer
What is being tested?: Almonertinib and Almonertinib plus carboplatin and pemetrexed
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 166 participants
Where: 6 sitesChina
Study dates: Oct 2020to Oct 2023
Phase: Phase 3
Are there results?: None posted in the registry

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 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Provision of informed consent prior to any study specific procedures, sampling and analyses.
Male or female, age at least 18 years.
Pathologically confirmed locally advanced or metastatic NSCLC (e.g. this may occur systemic recurrence after prior surgery for early stage disease or patients may be newly diagnosed with stage IIIB/IV disease according to AJCC v8.0). Patients must be treatment-naïve for locally advanced or metastatic NSCLC. provided all other entry criteria are satisfied.
Prior adjuvant, neo-adjuvant therapy and concurrent radiochemotherapy is permitted (chemotherapy, radiotherapy, investigational agents) if 6 months or more have passed since completion of therapy.
The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), in combination with non-EGFR driver genes mutations assessed by central testing using tumour tissue sample.
A WHO performance status equal to 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.

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At least 1 lesion that has not previously been irradiated, that has not been chosen for biopsy during the study screening period, and that can be accurately measured at Baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), whichever is suitable for accurately repeated measurements. If only one measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and baseline tumour assessment scans are done at least 14days afar the screening biopsy is performed.
Females should be using adequate contraceptive measures throughout the study; should not be breastfeeding at the time of screening, during the study and until 3 months after completion of the study; and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential by fulfilling 1 of the following criteria at Screening:
Postmenopausal defined as age more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more, following cessation of exogenous hormonal treatments, and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the laboratory.
Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not by tubal ligation.
Male patients should be willing to use barrier contraception (i.e., condoms).
For inclusion in study, patient must provide a written informed consent.

Who cannot join

Treatment with any of the following:
Prior treatment with systemic anti-cancer therapy for locally advancer or metastatic NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug.
Prior treatment with an EGFR TKI.
Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug.
Radiotherapy with a limited field of radiation for palliation within 4 week of the first dose of study drug, with the exception of patients receiving radiation to > 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
Medications that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of the first dose of study drug.

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Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.
Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 2 weeks prior to start of study treatment.
Patients who received yellow-fever vaccine or other attenuated live vaccine during pemetrexed treatment.
Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension or active bleeding diatheses, which, in the Investigator's opinion, makes it undesirable for the patient to participate in the trial OR which would jeopardize compliance with the protocol such as active infection. Screening for chronic conditions is not required.
Refractory nausea, vomiting, or chronic gastrointestinal diseases, inability to swallow the study drug, or previous significant bowel resection that would preclude adequate absorption of Almonertinib.
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., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval > 250 ms).
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval.
Left ventricular ejection fraction (LVEF) ≤ 40%.
Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis that required steroid treatment, or any evidence of clinically active interstitial lung disease.
Inadequate bone marrow reserve or organ function, as demonstrated by any of the following laboratory values:
Absolute neutrophil count (ANC) <1.5×109 / L
Platelet count <100×109 / L
Hemoglobin <90 g/L（<9 g/dL）
Alanine aminotransferase > 2.5 × upper limit of normal (ULN) if no demonstrable liver metastases or > 5 × ULN in the presence of liver metastases.
Aspartate aminotransferase (AST) > 2.5 × ULN if no demonstrable liver metastases or > 5 × ULN in the presence of liver metastases.
Total bilirubin (TBL) > 1.5 × ULN if no liver metastases or > 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases.
Creatinine > 1.5 × ULN concurrent with creatinine clearance < 50 mL/min (measured or calculated by the Cockcroft-Gault equation); confirmation of creatinine clearance is only required when creatinine is > 1.5 × ULN.
Women who are breastfeeding or have a positive urine or serum pregnancy test at the Screening Visit.
History of hypersensitivity to any active or inactive ingredient of Almonertinib, or to drugs with a similar chemical structure or class to Almonertinib.
Patients who are allergic to pemetrexed or any other component of the preparation, carboplatin or other platinum containing compounds.
Patients with contraindications of pemetrexed and carboplatin.
Any severe and uncontrolled ocular disease that may, in the ophthalmologist's opinion, present a specific risk to the patient's safety.
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 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

6 sites in 1 country.

Jie Wang contact

13910704669

jiewang_hr@sina.com

City, postcode or hospital

6 sites in 1 country

China6 sites

Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021
Beijing Cancer Hospital
Beijing
Jun Zhao
Beijing Chest Hospital, Capital Medical University
Beijing
Zhe Liu
Peking University International Hospital
Beijing
Chuanhao Tang
Tianjin Medical University Cancer Institute & Hospital
Tianjin
Ping Wang
Tianjin Medical University Cancer Institute & Hospital
Tianjin
Dingzhi Huang

Other trials in China

About this study

Official title: Almonertinib Alone Versus Almonertinib Plus Chemotherapy as First-line Treatment in Patients With Epidermal Growth Factor Receptor (EGFR) Mutation Positive With Concomitant Non-EGFR Driver Gene Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer: A Multicenter, Open-label, Randomized, Control Phase III Study (ACROSS 1)

This is a multicenter, randomized, controlled, phase III study.

Read the detailed description

Almonertinib Alone Versus Almonertinib Plus Chemotherapy as First-line Treatment in Patients With Epidermal Growth Factor Receptor (EGFR) Mutation Positive With Concomitant Non-EGFR Driver Gene Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer: A Multicenter, Open-label, Randomized, Control Phase III Study (ACROSS 1).

Conditions: Non Small Cell Lung Cancer
Being tested: Almonertinib, Almonertinib plus carboplatin and pemetrexed
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 Ameile
Almonertinib 110mg PO once daily. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Almonertinib plus carboplatin and pemetrexedDrug
Also called Ameile
Almonertinib 110mg PO once daily in combination with pemetrexed (500 mg/m2) plus carboplatin (AUC=5) on Day 1 of 21day cycles (every 3 weeks) for 4-6 cycles, followed by Almonertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.

Study groups in NCT04500704
Study group	Role	What they receive
Almonertinib 110mg PO once daily	Active comparator	Almonertinib 110mg PO once daily. Receives: Drug: Almonertinib
Almonertinib plus carboplatin and pemetrexed	Experimental	Almonertinib 110mg PO once daily in combination with pemetrexed (500 mg/m2) plus carboplatin (AUC=5) on Day 1 of 21day cycles (every 3 weeks) for 4-6 cycles, followed by Almonertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks. Receives: Drug: Almonertinib plus carboplatin and pemetrexed

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression Free Survival (PFS)
To assess the efficacy of Almonertinib compared with Almonertinib Plus carboplatin and pemetrexed as first line therapy to EGFRm+, locally advanced or metastatic NSCLC patients by assessment of progression free survival (PFS) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Measured: From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.

Secondary outcomes (6)

Assess the anti-tumor activity: OS
Overall survival (OS)
Measured: Start of study drug to Survival Endpoint through study completion, an average of 3 years.
Assess the anti-tumor activity: ORR
ORR is defined as the percentage of patients who have at least 1 response of CR or PR prior to any evidence of progression assessed up to 24 months
Measured: From baseline, then every 6 weeks, until disease progression or discontinuation from study. ORR is defined as the percentage of patients who have at least 1 response of CR or PR prior to any evidence of progression assessed up to 24 months.
Assess the anti-tumor activity: DCR
Disease control rate (DCR)
Measured: From baseline, then every 6 weeks, until disease progression or discontinuation from study. The DCR is defined as the proportion of patients with a best overall response of CR, PR, or SD assessed up to 24 months.
Assess the anti-tumor activity: DoR
Duration of response (DoR)
Measured: DoR is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression assessed up to 24 months.
Assess the anti-tumor activity: DepOR
Depth of response (DepOR)
Measured: From baseline, then every 6 weeks, until disease progression or discontinuation from study. DepOR is defined as the sum of the lengths of the longest diameters of the RECIST 1.1 target lesions up to 24 months.
Assess the safety of Almonertinib and Almonertinib plus pemetrexed and carboplatin: Number of AEs/SAEs
Number of adverse events (AEs)/serious adverse events (SAEs)
Measured: Continuously throughout the study until 28 days after Termination of the treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2020Oct 2023

First posted5 Aug 2020
Study startOct 2020 (estimated)
Primary completionDec 2021 (estimated)
Study completionOct 2023 (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 Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe 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: None (open label)
Enrolment: 166 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04500704
Sponsor's protocol ID: HS-LK-2020-001
Acronym: ACROSS1
Status last verified: Jul 2020
First submitted: 2 Aug 2020
Last updated: 5 Aug 2020
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 5 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Almonertinib Alone Versus Almonertinib Plus Chemotherapy as First-line Treatment in Patients With Epidermal Growth Factor Receptor (EGFR) Mutation Positive With Concomitant Non-EGFR Driver Gene Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer: A Multicenter, Open-label, Randomized, Control Phase III Study (ACROSS 1)
ClinicalTrials.gov ID: NCT04500704
Acronym / sponsor ID: ACROSS1 / HS-LK-2020-001
Conditions: Non Small Cell Lung Cancer
Phase: Phase 3
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 166 participants (estimated)
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
Collaborators: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study start: Oct 2020 (estimated)
Primary completion: Dec 2021 (estimated)
Study completion: Oct 2023 (estimated)
First posted: 5 Aug 2020 (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.

This is a multicenter, randomized, controlled, phase III study.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Almonertinib 110mg PO once daily	Active comparator	Drug: AlmonertinibAlmonertinib 110mg PO once daily.
Almonertinib plus carboplatin and pemetrexed	Experimental	Drug: Almonertinib plus carboplatin and pemetrexedAlmonertinib 110mg PO once daily in combination with pemetrexed (500 mg/m2) plus carboplatin (AUC=5) on Day 1 of 21day cycles (every 3 weeks) for 4-6 cycles, followed by Almonertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Provision of informed consent prior to any study specific procedures, sampling and analyses.
Male or female, age at least 18 years.
Pathologically confirmed locally advanced or metastatic NSCLC (e.g. this may occur systemic recurrence after prior surgery for early stage disease or patients may be newly diagnosed with stage IIIB/IV disease according to AJCC v8.0). Patients must be treatment-naïve for locally advanced or metastatic NSCLC. provided all other entry criteria are satisfied.
Prior adjuvant, neo-adjuvant therapy and concurrent radiochemotherapy is permitted (chemotherapy, radiotherapy, investigational agents) if 6 months or more have passed since completion of therapy.
The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), in combination with non-EGFR driver genes mutations assessed by central testing using tumour tissue sample.

Key exclusion criteria (33 listed)

Treatment with any of the following:
Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.
Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 2 weeks prior to start of study treatment.
Patients who received yellow-fever vaccine or other attenuated live vaccine during pemetrexed treatment.

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: AmeileAlmonertinib 110mg PO once daily. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Drug	Almonertinib 110mg PO once daily
Almonertinib plus carboplatin and pemetrexedAlso: AmeileAlmonertinib 110mg PO once daily in combination with pemetrexed (500 mg/m2) plus carboplatin (AUC=5) on Day 1 of 21day cycles (every 3 weeks) for 4-6 cycles, followed by Almonertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.	Drug	Almonertinib plus carboplatin and pemetrexed

Primary outcome

Progression Free Survival (PFS)
Time frame: From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
To assess the efficacy of Almonertinib compared with Almonertinib Plus carboplatin and pemetrexed as first line therapy to EGFRm+, locally advanced or metastatic NSCLC patients by assessment of progression free survival (PFS) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

6 secondary outcomes

Assess the anti-tumor activity: OS
Time frame: Start of study drug to Survival Endpoint through study completion, an average of 3 years.
Assess the anti-tumor activity: ORR
Time frame: From baseline, then every 6 weeks, until disease progression or discontinuation from study. ORR is defined as the percentage of patients who have at least 1 response of CR or PR prior to any evidence of progression assessed up to 24 months.
Assess the anti-tumor activity: DCR
Time frame: From baseline, then every 6 weeks, until disease progression or discontinuation from study. The DCR is defined as the proportion of patients with a best overall response of CR, PR, or SD assessed up to 24 months.
Assess the anti-tumor activity: DoR
Time frame: DoR is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression assessed up to 24 months.
Assess the anti-tumor activity: DepOR
Time frame: From baseline, then every 6 weeks, until disease progression or discontinuation from study. DepOR is defined as the sum of the lengths of the longest diameters of the RECIST 1.1 target lesions up to 24 months.
Assess the safety of Almonertinib and Almonertinib plus pemetrexed and carboplatin: Number of AEs/SAEs
Time frame: Continuously throughout the study until 28 days after Termination of the treatment

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2020.
Individual participant dataSharing planned: No

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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. This study is not recruiting at the moment.

Jie Wang contact

13910704669

jiewang_hr@sina.com

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 13 inclusion and 33 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: status not confirmed, as of the sponsor's last update on 5 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites 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. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jie Wang (13910704669, jiewang_hr@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04500704.

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 5 Aug 2020.