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For adenocarcinoma, either:

* Aumolertinib + cisplatin with pemetrexed, or
* Aumolertinib + carboplatin with pemetrexed

For squamous cell carcinoma, one of the following:

* Aumolertinib + cisplatin or carboplatin with paclitaxel;
* Aumolertinib + cisplatin or carboplatin with albumin-bound paclitaxel; or
* Aumolertinib + cisplatin or carboplatin with gemcitabine

Administered orally, once daily as two 55-mg tablets for a total dose of 110 mg.

Aumolertinib monotherapy

80 mg tablet administered orally, once daily

Osimertinib monotherapy

Administered by IV Infusion per prescribing information. Maybe be continued as maintenance therapy

Administered by IV Infusion given over 4 fixed cycles (q3wk × 4 cycles) per prescribing information.

Administered by IV Infusion given over 4 -6 fixed cycles per prescribing information.

Administered by IV Infusion given over 4 fixed cycles per prescribing information.

Nab paclitaxel

Administered by IV Infusion over 4 fixed cycles per prescribing information.

Aumolertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets EGFR mutations. The reason for this study is to learn whether adding chemotherapy to a new investigational drug called aumolertinib helps to slow or stop cancer growth in people with EGFR mutation-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC). The study will compare this new combination of drugs to osimertinib, given alone. Aumolertinib given alone will also be used in the study, and it will be looked at in comparison with osimertinib given alone.

This is a randomized, open-label study with 3 different groups that are listed below. "Randomized" means the study treatment participants take will be chosen by chance (decided at random by a computer). "Open-label" means that the participant, the study doctor, and the Sponsor will know which study treatment each participant is receiving.

Participants will be randomly assigned to one of the following 3 treatment groups:

* Group 1: Treatment with aumolertinib alone, taken orally (by mouth) as a pill once a day. Around 100 participants will be randomly assigned to this group.
* Group 2: Treatment with aumolertinib taken orally as a pill once a day, in combination with chemotherapy given intravenously (IV; through a needle placed in a vein) on the schedule provided by the study doctor. Around 200 participants will be randomly assigned to this group.
* Group 3: Treatment with osimertinib alone, taken orally as a pill once a day. Around 200 participants will be randomly assigned to this group.

Because there will be twice as many participants in Group 2 and Group 3 as in Group 1, the chance of a participant being randomly assigned to either of those groups is twice as likely as being assigned to Group 1.

Participants can continue to receive study treatment as long as they have not withdrawn consent, as long as they choose to continue to receive study treatment and are judged by their doctor to continue to receive clinical benefit from receiving the study treatment, and as long as no other study treatment and/or study discontinuation criteria are met .

Aumolertinib With Chemotherapy or Alone Compared With Osimertinib in Patients With Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer

A Randomized, Three-Arm, Open-Label Phase 3b Clinical Trial of Aumolertinib, Versus Aumolertinib With Chemotherapy, Versus Osimertinib for Patients With Metastatic NSCLC and an EGFR Mutation (TREBLE)

PFS is defined as the time from date of randomization until date of disease progression or death due to any cause, whichever occurs first.

OS is defined as the time from date of randomization until death from any cause.

ORR is defined as proportion of participants who achieve a complete response or partial response at any time before progressive disease or initiating a subsequent anticancer therapy.

DCR is defined as the proportion of participants who have a best overall response of complete response or partial response or stable disease.

TGR is defined as the constant exponential growth rate estimated using the sum of longest diameters based on radiological tumor assessment per RECIST v1.1.

DOR is defined as date of first response (complete response or partial response) until date of disease progression or death due to any cause, whichever occurs first

DepOR is defined as the relative change in target lesion tumor size (calculated as the sum of the longest diameters of the target lesions, in the absence of new lesions or progression of nontarget lesions) as compared to baseline.

ORR is defined as the proportion of participants who achieve a complete response or partial response at any time before disease progression or initiating a subsequent anticancer therapy.

DOR is defined as date of first response (complete response or partial response) until the date of disease progression or death due to any cause, whichever occurs first.

NCI PRO-CTCAE questionnaire responses are scored from 0 to 4, wherein lower values represent a better outcome. For this trial, the burden of symptoms that will be captured by this questionnaire comprises nausea, diarrhea, and rash.

ctDNA clearance is defined as when a detectable EGFR mutation in ctDNA at baseline becomes undetectable or drops below a predetermined threshold. Rate of ctDNA clearance is defined as 100 × number of participants who are ctDNA-negative at 6 weeks divided by number of participants who are ctDNA-positive at baseline.

Plasma concentration is defined as the measured drug concentration of aumolertinib.

Plasma concentration is defined as the measured drug concentration of aumolertinib metabolite.

This outcome will evaluate the incidence of participants with TEAEs, graded according to NCI CTCAE V5.

This outcome will evaluate incidence of participants with SAEs, be graded according to NCI CTCAE V5.

This outcome will evaluate incidence of participants with ECG abnormalities

This outcome will evaluate incidence of participants with laboratory abnormalities, graded according to NCI CTCAE V5.

EQRx International, Inc.

The trial was discontinued at 8 months. No patients were analyzed.

Aumolertinib monotherapy: Administered orally, once daily as two 55-mg tablets for a total dose of 110 mg.

Aumolertinib Monotherapy

For adenocarcinoma, either:

* Aumolertinib + cisplatin with pemetrexed, or
* Aumolertinib + carboplatin with pemetrexed

For squamous cell carcinoma, one of the following:

* Aumolertinib + cisplatin or carboplatin with paclitaxel;
* Aumolertinib + cisplatin or carboplatin with albumin-bound paclitaxel; or
* Aumolertinib + cisplatin or carboplatin with gemcitabine

Aumolertinib monotherapy: Administered orally, once daily as two 55-mg tablets for a total dose of 110 mg.

Pemetrexed: Administered by IV Infusion per prescribing information. Maybe be continued as maintenance therapy

Cisplatin: Administered by IV Infusion given over 4 fixed cycles (q3wk × 4 cycles) per prescribing information.

Carboplatin: Administered by IV Infusion given over 4 fixed cycles (q3wk × 4 cycles) per prescribing information.

Paclitaxel: Administered by IV Infusion given over 4 -6 fixed cycles per prescribing information.

Nab paclitaxel: Administered by IV Infusion given over 4 fixed cycles per prescribing information.

Gemcitabine: Administered by IV Infusion over 4 fixed cycles per prescribing information.

Aumolertinib + Platinum-based Doublet Chemotherapy

Osimertinib monotherapy: 80 mg tablet administered orally, once daily

Osimertinib Monotherapy

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Study terminated early, no participants completed the study, no participants were analyzed.

EQRx Clinical Trials

data not collected, 0 participants analyzed

Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Overall Survival (OS)

Objective Response Rate (ORR) as Assessed by BICR Per RECIST v1.1

Disease Control Rate (DCR) as Assessed by BICR Per RECIST v1.1

Tumor Growth Rate (TGR) as Assessed by BICR Per RECIST v1.1

Duration of Response (DOR) as Assessed by BICR Per RECIST v1.1

Depth of Response (DepOR) as Assessed by BICR Per RECIST v1.1

PFS as Assessed by the Investigator Per RECIST v1.1

ORR as Assessed by the Investigator Per RECIST v1.1

DCR as Assessed by the Investigator Per RECIST v1.1

TGR as Assessed by the Investigator Per RECIST v1.1

DOR as Assessed by the Investigator Per RECIST v1.1

DepOR as Assessed by the Investigator Per RECIST v1.1

Quality of Life as Assessed by the National Cancer Institute Patient Reported Outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) Questionnaire

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Aumolertinib With Chemotherapy or Alone Compared With Osimertinib in Patients With Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer	NCT05493501	NSCLC	Aumolertinib mo... Osimertinib mon... Pemetrexed Cisplatin Carboplatin Paclitaxel Nab paclitaxel Gemcitabine	18 Years -	EQRx International, Inc.
Aumolertinib With Chemotherapy or Alone Compared With Osimertinib in Patients With Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer	NCT05493501	NSCLC	Aumolertinib mo... Osimertinib mon... Pemetrexed Cisplatin Carboplatin Paclitaxel Nab paclitaxel Gemcitabine	18 Years -	EQRx International, Inc.
Aumolertinib With Chemotherapy or Alone Compared With Osimertinib in Patients With Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer	NCT05493501	NSCLC	Aumolertinib mo... Osimertinib mon... Pemetrexed Cisplatin Carboplatin Paclitaxel Nab paclitaxel Gemcitabine	18 Years -	EQRx International, Inc.

Spots Global Cancer Trial Database for osimertinib monotherapy