Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Micronutrients

Hematinics

Amino Acids

Vitamins

Antibodies

Carboplatin

Pemetrexed

Immunoglobulins

Mitogens

Tyrosine Kinase Inhibitors

Lazertinib

Amivantamab-vmjw

Antibodies, Bispecific

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Protein Kinase Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Tyrosine

Folinic Acid

Folate

Vitamin B9

The first cohort of participants will receive intravenous (IV) infusions of Amivantamab 140 milligram (mg) as monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased dose level. Dose escalation will continue until maximum tolerated dose is reached or all planned doses are administered. Participants will receive IV infusion of Amivantamab once weekly during cycle 1 and once every 2 weeks during subsequent cycles (duration of each treatment cycle is 28 days). Participants will receive lazertinib and Amivantamab on Cycle 1 Day 1 (C1D1) prior to initiation of Amivantamab (C1D1) at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily thereafter, on 28-day Amivantamab treatment cycle. In Chemotherapy Combination Cohort, participants will receive Amivantamab, administered on a 21-day cycle, in combination with standard of care carboplatin and pemetrexed.

Participants will receive IV infusion of Amivantamab as monotherapy at Phase 2 dose (RP2D) regimen or in combination lazertinib at the recommended Phase 2 combination dose (RP2CD) regimen as determined in Part 1. The purpose of dose expansion is to further evaluate safety, tolerability, pharmacokinetic, and to assess preliminary efficacy in monotherapy and combination therapy cohorts.

The first cohort of participants will receive IV infusions of Amivantamab 140 mg as monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased dose level until maximum tolerated dose is reached or all planned doses are administered. Participants will receive lazertinib and Amivantamab at predefined dose levels, based upon observed safety and protocol defined criteria. The duration of each treatment cycle is 28 days. In Chemotherapy Combination Cohort, participants will receive Amivantamab, administered on a 21-day cycle, in combination with the administration of standard of care carboplatin and pemetrexed.

Amivantamab

Participants will receive IV infusion of Amivantamab as monotherapy at RP2D regimen or in combination lazertinib at RP2CD regimen as determined in Part 1.

Lazertinib will be administered in combination with Amivantamab at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily on the 28-day Amivantamab treatment cycle.

Participants will receive carboplatin in combination with pemetrexed and Amivantamab as an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.

Participants will receive pemetrexed in combination with carboplatin and Amivantamab as an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.

Janssen Research & Development, LLC Clinical Trial

The purpose of study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of Amivantamab as a monotherapy and in combination with lazertinib, and to determine the recommended Phase 2 dose (RP2D) (monotherapy), recommended Phase 2 combination dose (RP2CD) (combination therapy), and to determine recommended Phase 2 Dose (RP2q3W) with combination chemotherapy (Amivantamab in combination with standard of care carboplatin and pemetrexed) in 21 day treatment cycle for participants with advanced non-small cell lung cancer (NSCLC).

This open label (all participants know the identity of the study drug), multicenter (more than one study site), first-in-human study consists of 2 parts. Part 1 is a Amivantamab Monotherapy and Combination Dose Escalations and Part 2 Amivantamab Monotherapy and Combination Dose Expansions. In Part 1, participants with evaluable NSCLC will be enrolled into cohorts at increasing dose levels of Amivantamab monotherapy, the RP2CD of the Amivantamab and lazertinib combination which will be administered in 28 day treatment cycles, and RP2q3W of Amivantamab in combination with standard of care carboplatin and pemetrexed (chemotherapy combination) which will be administered in 21 day treatment cycles. The dose will be escalated until the maximum tolerated dose (MTD, or maximum administered dose \[MAD\], if no MTD is found) is reached. Part 1 will follow a traditional 3+3 design. At each dose level, 3 participants will complete Cycle 1. If no dose limiting toxicity (DLT) occurs in these 3 participants, then escalation will continue in a new cohort of 3 participants. Data from Part 1 will be used to determine one or more RP2D regimen(s). In Part 2, participants with documented epidermal growth factor receptor (EGFR) mutations and measurable disease, whose disease has progressed after previous treatment will be enrolled and receive Amivantamab at the RP2D determined in Part 1 as a monotherapy at the RP2D regimen(s), or in combination with lazertinib at the RP2CD regimen. For both parts, the study consists of following periods: an optional pre-Screening period; a Screening period (up to 28 days prior to the first dose of study drug); a Treatment period (first dose of study drug until 30(+7) days after the last dose of study drug or prior to starting any subsequent anti-cancer treatment, whichever comes first); and a Follow Up period (approximately 6 months). All participants will be followed for survival in the post-treatment follow-up period until the end of study and safety will be monitored throughout the study.

Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer

A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Subjects With Advanced Non-Small Cell Lung Cancer

The Dose Limiting Toxicity (DLT) is based on drug related adverse events and includes unacceptable hematologic toxicity, non-hematologic toxicity of Grade 3 or higher, or elevations in hepatic enzymes suggestive of drug-induced liver injury.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Overall response rate (ORR) is defined as the percentage of participants who achieve either a CR or PR as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). CR: disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (\< 10 mm short axis) and normalisation of tumour marker levels; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and Persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

DOR will be calculated as time from initial response of CR (disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (\[\<\] 10 \[mm\] short axis) and normalisation of tumour marker levels) or PR (at least a 30 \[%\] decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits) to progressive disease (PD) or death due to underlying disease, whichever comes first, only for participants who achieve CR or PR.

Clinical benefit rate is defined as the percentage of participants achieving complete response (CR): disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (less than \[\<\] 10 millimeter \[mm\] short axis) and normalisation of tumour marker levels or partial response (PR): at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

Ctrough is the observed serum concentration immediately prior to the next administration.

The AUCtau is the area under the serum concentration-time curve during a dose interval time period (tau)

The Cmax is the maximum observed serum concentration of Amivantamab.

The Tmax is defined as time to reach maximum observed serum concentration of Amivantamab.

The AUC(t1-t2) is the area under the serum Amivantamab concentration-time curve from time t1 to t2.

The Ctrough is the observed serum concentration immediately prior to the next administration.

Cmax is the maximum observed serum concentration of lazertinib.

Tmax is defined as time to reach maximum observed serum concentration of lazertinib.

The R is the accumulation ratio calculated as Cmax or AUC after multiple doses divided by Cmax or AUC after the first dose, respectively.

Serum levels of antibodies to Amivantamab for evaluation of potential immunogenicity.

PFS is defined as the time from first infusion of study drug to PD or death due to any cause.

TTF is defined as the time from the first infusion of the study drug to discontinuation of treatment for any reason, including disease progression, treatment toxicity, death, and will be utilized to capture clinical benefit for patients continuing treatment beyond RECIST v1.1 defined disease progression.

OS is defined as the time from first infusion of study drug to death due to any cause.

Janssen Research & Development, LLC

Adenocarcinoma

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Bronchial Diseases

Osimertinib

Phase 1 dose escalation of BLU-945 as monotherapy at various dose levels

Phase 1 dose escalation of BLU-945 in combination with osimertinib 80 mg tablets for oral administration

Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR T790M and C797S mutations

Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR T790M mutations

Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR C797S mutations

Phase 2 expansion group for BLU-945 with osimertinib at a dose determined during Part 1B in patients

BLU-945

Osimertinib tablets for oral administration

osimertinib

This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of BLU-945, a selective EGFR inhibitor, as monotherapy or in combination with osimertinib.

The study will include an initial Phase 1 portion to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BLU-945 as monotherapy (initially in a QD regimen with the option to evaluate BID dosing, if supported by emerging PK and safety data), as well as an additional dose-escalation portion to determine the RP2D of BLU-945 in combination with osimertinib. The BLU-945 monotherapy Phase 2 expansion groups will consist of patients with tumors harboring specific mutation profiles (EGFR T790M and C797S mutation \[Group 1\]; EGFR T790M but not C797S \[Group 2\]; or EGFR C797S but not T790M \[Group 3\]). The BLU-945 with osimertinib Phase 2 expansion (Group 4) will include approximately 24 evaluable patients, with at least 12 slots reserved for patients with EGFR T790M and C797S mutation.

(SYMPHONY) Phase 1/2 Study Targeting EGFR Resistance Mechanisms in NSCLC

A Phase 1/2 Study Targeting Acquired Resistance Mechanisms in Patients With EGFR Mutant Non-Small Cell Lung Cancer

MTD determination: dose limiting toxicity (DLT) rate

RP2D determination: DLT, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary safety and anticancer activity data

ORR, defined as the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1

DOR, defined as the time from first documented response of complete response (CR) or partial response (PR) to the date of first documented progressive disease or death due to any cause, whichever occurs first

Profile pharmacodynamic changes in the EGFR pathway biomarker expression levels of dual specificity phosphatase (DUSP6) and sprouty RTK signaling antagonist 4 (SPRY4).

DCR, defined as the proportion of patients who experience a best response of CR, PR, or stable disease (SD) according to RECIST 1.1

CBR, defined as the proportion of patients who experience a confirmed CR or PR, or stable disease (SD) with a duration of at least 16 weeks according to RECIST 1.1

PFS, defined as the time from the first dose of BLU-945 until the date of first documented progressive disease or death due to any cause, whichever occurs first

OS, defined as the time from the first dose of BLU-945 until the date of death due to any cause

CNS-ORR - proportion of patients with measurable (target) intracranial metastases at baseline who experience a confirmed intracranial CR or PR according to RECIST 1.1 principles

CNS-DOR - time from first documented intracranial CR or PR to the date of first documented intracranial PD

CNS progression rate - proportion of patients with CNS progression as a component of first disease progression on study

Effects of BLU-945 on ECG parameters extracted from continuous 12 lead Holter recordings

Blueprint Medicines Corporation

Symptoms and General Pathology

Disease Progression

Dacomitinib

Participants in this cohort have a somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy.

Participants in this cohort have a secondary acquired EGFR mutation in addition to the sensitizing mutation

Cohort 1 Dacomitinib Dosing:

Dose level 1: Dacomitinib 45mg daily Dose level -1: Dacomitinib 30mg daily Dose level -2: Dacomitinib 15mg daily

Cohort 2 Dacomitinib Dosing:

Dose level 1: Dacomitinib 30 mg daily Dose level -1: Dacomitinib 15 mg daily

In cohort 2, participants will begin on dacomitinib orally daily in combination with Osimertinib

Dose level Osimertinib Dosing:

Dose level 1: Osimertinib 80 mg daily Dose level -1: Osimertinib 40 mg daily

Helen Yu, MD

The purpose of this study is to assess whether dacomitinib after osimertinib is effective in participants with metastatic EGR-mutant lung cancers.

A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progression on Osimertinib.

A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progressionon Osimertinib.

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Overall response rate (partial and complete responses) of dacomitinib in participants with EGFR-mutant lung cancers and disease progression on osimertinib

Memorial Sloan Kettering Cancer Center

Phase 1 dose escalation of BLU-701 as monotherapy at various dose levels

BLU-701 in combination with osimertinib 40 mg or 80 mg tablets for oral administration

BLU-701 in combination with platinum-based chemotherapy (carboplatin and pemetrexed):

Carboplatin - IV infusion dosed to target AUC of 5-6 mg/mL min q3w

Pemetrexed - IV infusion dosed to 500 mg/m2 q3w

Phase 2 expansion group for BLU-701 as monotherapy at a dose determined during Part 1A in patients harboring the EGFR C797X resistance mutation

BLU-701

carboplatin

pemetrexed

This is a Phase 1/2, open-label, first-in-human (FIH) study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of BLU-701 as monotherapy or in combination with either osimertinib or platinum-based chemotherapy in patients with EGFRm NSCLC.

The study was planned to include an initial Phase 1 portion to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BLU-701 as monotherapy (Part 1A; initially in a once daily (QD) regimen with the option to evaluate twice daily (BID) dosing if supported by emerging PK and safety data), as well as additional dose-escalation portions to determine the RP2D of BLU-701 in combination with osimertinib (Part 1B) or in combination with carboplatin and pemetrexed (Part 1C). A Phase 2 part was planned to further evaluate the efficacy and safety of BLU-701 as monotherapy at RP2D (Part 2A). Phase 1 Part 1 A was initiated; however, the study was terminated prior to establishing BLU-701 MTD and/or RP2D.

(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC

A Phase 1/2 Study of the Highly Selective EGFR Inhibitor, BLU-701, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer

RP2D determination: DLT, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary safety and antitumor activity data

ORR - the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1

ORR - the proportion of patients who experience a best response of confirmed complete response (CR) or partial response (PR) according to RECIST 1.1

DOR - time from first documented response of CR or PR to the date of first documented progressive disease or death due to any cause, whichever occurs first

maximum plasma drug concentration (Cmax) time to maximum plasma drug concentration (Tmax) time of last quantifiable plasma drug concentration (Tlast) area under the plasma concentration versus time curve from time 0 to the end of the dosing interval (AUC0-24 for QD and AUC0-12 for BID) trough concentration (Ctrough) apparent volume of distribution (Vz/F) terminal elimination half-life (t½) apparent oral clearance(CL/F) accumulation ratio (R)

dual specificity phosphatase (DUSP6)

sprouty RTK signaling antagonist 4 (SPRY4)

DCR - proportion of patients who experience a best response of CR, PR, or SD according to RECIST 1.1

CBR - proportion of patients who experience a confirmed CR or PR, or SD with a duration of at least 16 weeks according to RECIST 1.1

PFS - time from the first dose of BLU-701 until the date of first documented PD or death due to any cause

OS - time from the first dose of BLU-701 until the date of death due to any cause

ECG parameters extracted from continuous 12-lead Holter recordings

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer	NCT02609776	Non-Small-Cell ...	Amivantamab Amivantamab Lazertinib Carboplatin Pemetrexed	18 Years -	Janssen Research & Development, LLC
(SYMPHONY) Phase 1/2 Study Targeting EGFR Resistance Mechanisms in NSCLC	NCT04862780	Lung Neoplasms Carcinoma, Non-... Respiratory Tra... Neoplasms Neoplasms by Si... Lung Diseases Respiratory Tra... Carcinoma, Bron... Bronchial Neopl... Adenocarcinoma Carcinoma Neoplasms by Hi... Neoplasms, Nerv... EGFR T790M EGFR C797S EGFR L858R EGFR Gene Mutat... EGF-R Positive ... EGFR Exon 19 De... EGFR Mutation R... EGFR Activating... Protein Kinase ... Antineoplastic ... Thoracic Neopla...	BLU-945 osimertinib	18 Years -	Blueprint Medicines Corporation
A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progression on Osimertinib.	NCT03755102	EGFR Gene Mutat... Lung Cancer Lung Cancer Met...	Dacomitinib Osimertinib	18 Years -	Memorial Sloan Kettering Cancer Center
(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC	NCT05153408	Lung Neoplasm Carcinoma, Non-... Respiratory Tra... Neoplasms Neoplasms by Si... Lung Diseases Respiratory Tra... Carcinoma, Bron... Bronchial Neopl... Adenocarcinoma Carcinoma Neoplasms by Hi... Neoplasms, Nerv... EGFR C797S EGFR C797A EGFR L858R EGFR Exon 19 De... EGFR Gene Mutat... EGF-R Positive ... EGFR Mutation R... EGFR Activating... Thoracic Neopla... Antineoplastic ... Protein Kinase ... EGFR C797G EGFR C797X Non Small Cell ...	BLU-701 osimertinib carboplatin pemetrexed	18 Years -	Blueprint Medicines Corporation
(SYMPHONY) Phase 1/2 Study Targeting EGFR Resistance Mechanisms in NSCLC	NCT04862780	Lung Neoplasms Carcinoma, Non-... Respiratory Tra... Neoplasms Neoplasms by Si... Lung Diseases Respiratory Tra... Carcinoma, Bron... Bronchial Neopl... Adenocarcinoma Carcinoma Neoplasms by Hi... Neoplasms, Nerv... EGFR T790M EGFR C797S EGFR L858R EGFR Gene Mutat... EGF-R Positive ... EGFR Exon 19 De... EGFR Mutation R... EGFR Activating... Protein Kinase ... Antineoplastic ... Thoracic Neopla...	BLU-945 osimertinib	18 Years -	Blueprint Medicines Corporation

Spots Global Cancer Trial Database for egfr c797s

Every month we try and update this database with for egfr c797s cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for egfr c797s

Every month we try and update this database with for egfr c797s cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for egfr c797s cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.