Aumolertinib Alone and With Chemotherapy in Patients With EGFR-Mutant Non-Small Cell Lung Cancer
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of aumolertinib and chemotherapy versus aumolertinib alone, along with an osimertinib reference arm, in systemic treatment-naïve participants who have metastatic EGFR-mutant NSCLC and an ECOG PS of 0, 1, or 2.
Additional study details include the following:
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The study duration will be approximately 5 years.
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Participants can continue to receive treatment as long as they are judged by the Investigator to continue to receive clinical benefit in the absence of meeting the discontinuation criteria
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Aumolertinib alone (approximately 140 participants)
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Drug: Aumolertinib
In this study, aumolertinib will be orally administered as two 55-mg tablets for a total dose of 110 mg. Participants randomized to receive chemotherapy will receive up to 4 cycles of a platinum-based doublet with daily aumolertinib 110 mg once orally; thereafter, participants may receive maintenance pemetrexed therapy and daily aumolertinib at Investigator discretion
Other Names:
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Experimental: Aumolertinib + Chemotherapy (approximately 140 participants) Aumolertinib + either cisplatin OR carboplatin with pemetrexed (for adenocarcinoma), OR aumolertinib + a platin with paclitaxel, albumin-bound paclitaxel, docetaxel, or gemcitabine (for squamous cell carcinoma) |
Drug: Aumolertinib
In this study, aumolertinib will be orally administered as two 55-mg tablets for a total dose of 110 mg. Participants randomized to receive chemotherapy will receive up to 4 cycles of a platinum-based doublet with daily aumolertinib 110 mg once orally; thereafter, participants may receive maintenance pemetrexed therapy and daily aumolertinib at Investigator discretion
Other Names:
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Active Comparator: Osimertinib alone (approximately 140 participants)
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Drug: Osimertinib
Osimertinib (tablet) will be administered daily at 80 mg once orally
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Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) [From date of randomization until the date of disease progression or death due to any cause, assessed up to 5 years]
Secondary Outcome Measures
- Overall Survival (OS) [From randomization to end of study or date of death from any cause, whichever comes first, assessed every 12 weeks up to 5 years]
Overall survival is defined as the time from the date of randomization until death from any cause
- Objective Response Rate (ORR) [Up to 5 years]
Proportion of participants who achieve a CR or PR at any time before PD or initiating a subsequent anticancer therapy
- Disease Control Rate (DCR) [From date of baseline until the date of disease progression or discontinuation from study, assessed up to 5 years]
Proportion of participants who have a best overall response of CR or PR or SD
- Tumor Response [Up to 5 years]
Serial analysis of tumor measurements
- Duration of Response (DOR) [Up to 5 years]
Date of first response (CR or PR) until the date of PD or death due to any cause, whichever occurs first
- ctDNA Clearance [Up to 5 years]
When a detectable EGFR mutation in ctDNA at baseline becomes undetectable or drops below a predetermined threshold at 6 weeks
- Plasma concentration of aumolertinib [Up to approximately 5 months]
Plasma concentration is defined as the measured drug concentration of aumolertinib
- To assess safety in study treatment arms [From the date of treatment start until discontinuation from treatment (plus 28 days for TEAEs), up to 5 years]
Treatment-emergent adverse events (TEAEs)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Is at least 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) and capable of complying with study procedures.
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Has pathologically confirmed NSCLC that is Stage IIIB (for selected participants who are not candidates for curative approaches per the treating Investigator), metastatic (Stage IVA or IVB), or recurrent, and which is not amenable to curative intent therapy.
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Tumor harbors one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity-ex19del or L858R-either alone or in combination with other EGFR mutations (eg, G719X, exon 20 insertions, S7681, L861Q), as identified by tissue or blood testing via a Clinical Laboratory Improvement Amendments of 1988 (CLIA)- certified laboratory.
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Has ECOG PS of 0, 1, or 2 at the time of enrollment.
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Has adequate organ function, as defined by all of the following:
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AST and ALT ≤ 3 × ULN
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TBIL ≤ 1.5 × ULN
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CREAT ≤ 1.5 × ULN OR calculated Ccr ≥ 50 mL/min
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ANC ≥ 1000 cells/mm3
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HGB ≥ 8.0 g/dL
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PLAT ≥ 100,000/mm3
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Must meet all of the applicable requirements for pregnancy and contraception, as follows:
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Female participants:
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Is a woman of childbearing potential who:
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Has a negative serum pregnancy test
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Is not breastfeeding
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Agree to use highly effective contraceptive measures while receiving study drug
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Agree not to donate while receiving study drug
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Is a woman of nonchildbearing potential (WONCBP) who:
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Is surgically sterile
- Male participants:
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Agree to use a highly effective method of contraception
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Agree to refrain from donating sperm for the same time period.
Exclusion Criteria:
- Medical Conditions:
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Has refractory nausea and vomiting, chronic gastrointestinal disease(s), inability to swallow the formulated product (or for selected participants, to receive it by PEG tube as noted below), or a history of previous significant bowel resection-any of which would preclude adequate absorption of aumolertinib or osimertinib.
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Has an active diagnosis of interstitial lung disease or pneumonitis.
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Has evidence of active bacterial, viral, or fungal infection
Prior/Concomitant Therapy:
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Has received prior systemic treatment for metastatic NSCLC. Note: Prior chemotherapy or immunotherapy is permitted, provided that a) it was used for treatment of locoregional NSCLC as a component of curative intent therapy and b) administration was completed more than 6 months ago.
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Is a candidate for curative intent therapy for the NSCLC diagnosis.
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Tumor has mixed small-cell and non-small-cell pathology.
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Meets any of the following cardiac criteria:
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Has any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, including evidence of QT prolongation (QTc >470 for males and >480 for females
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Has any factor, including any current medication(s), known to increase the risk of QTc prolongation or the risk of arrhythmic events
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | SCRI - Tennessee Oncology PLLC- Chattanooga | Chattanooga | Tennessee | United States | 37404 |
2 | SCRI - Tennessee Oncology- Nashville | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- EQRx International, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EQ143-301
- 2022-002674-93