Lung Cancer Clinical Trial

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

Summary

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).

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Full Description

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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Participant must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) that is metastatic or unresectable. Participants must have either progressed after prior standard of care therapy (Cohorts C and hepatocyte growth factor receptor gene [MET]-1: epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKI]; Cohort D: platinum-based chemotherapy; MET-2: per regional standard of care; Cohorts wild-type adenocarcinoma (WT-Ad) and wild-type squamous cell carcinoma (WT-Sq): platinum-containing chemotherapy and programmed death- 1/ ligand-1 (PD-1/L1) therapy, either as a combined regimen or as separate lines of therapy) for metastatic disease, or be ineligible for, or have refused all other currently available therapeutic options. In cases where participants refuse currently available therapeutic options, this must be documented in the study records. For Part 1 Chemotherapy Combination Cohort only: Participants must have histologically or cytologically confirmed NSCLC that is metastatic or unresectable and be eligible for treatment with combination carboplatin and pemetrexed, in accordance with standard of care, and be willing to receive additional investigational therapy with Amivantamab
For Part 1 Combination Dose Escalation with lazertinib only: Participants must have been diagnosed with EGFR Exon 19del or L858R activating mutation and (a) be treatment naïve for metastatic disease, without access to third generation TKI in the front-line setting, or (b) have progressed after front-line treatment with first (erlotinib or gefitinib) or second generation (afatinib) TKI and are ineligible for Cohort MET-1, or (c) have been treated with a third generation TKI (e.g., osimertinib) in either the front line or second-line setting, and are not eligible for enrollment in either Cohort C or MET-1. For Part 1 Chemotherapy Combination Cohort: Participants may be diagnosed with EGFR mutated or EGFR wild type NSCLC. For Part 2 Cohorts C, D, MET-1, and MET-2 only: Participants must also have disease with a previously diagnosed activating epidermal growth factor receptor (EGFR) mutation (includes both inhibitor sensitive primary mutations such as Exon 19 deletion and L858R (Cohort C, E, and MET-1), as well as marketed TKI-resistant mutations such as Exon 20 insertion (Cohort C, D and MET-1) or activating cMet Exon 14 skipping mutation (Cohort MET-2). Documentation of primary activating EGFR or cMet mutation eligibility by CLIA-certified laboratory (or equivalent) testing is required. For Part 2 Cohorts WT-Ad and WT-Sq: Participants must have wild-type EGFR, anaplastic lymphoma kinase (ALK), and absence of MET Exon 14 skipping mutation as tested by the Food and Drug Administration (FDA) approved test or a CLIA-certified laboratory (or equivalent). The pathology report or equivalent must be in the medical record for verification. Where testing for EGFR and ALK are not part of standard of care for participants with squamous cell carcinoma histology, documentation of the absence of these mutations is not necessary for enrollment into the WT-Sq cohort
For Part 1: Participant must have evaluable disease. For Part 2: Participant must have measurable disease according to Response Criteria in Solid Tumors (RECIST) v1.1
For Part 2: Cohorts A and B: Participants EGFR mutated disease must have most recently progressed following treatment with a marketed EGFR inhibitor. Exception: In participants diagnosed with mutations associated with de novo EGFR inhibitor resistance (for example, Exon 20 insertions), only previous treatment with combination platinum-based chemotherapy is required. Cohort C: Participants with primary EGFR mutated disease, with a documented EGFR alteration (example, C797S) mediating resistance to previous treatment with a third generation EGFR TKI (for example, osimertinib), in participants with primary Exon 20ins disease, the documented EGFR alteration may arise following treatment with a TKI with known activity against Exon 20ins disease (for example, poziotinib). Cohort D: participants must have been previously diagnosed with an EGFR Exon 20 insertion and have not been previously treated with a TKI with known activity against Exon 20ins disease (example, poziotinib). Cohort MET-1: Participants with documented primary EGFR mutated disease and documented MET amplification or MET mutation after progression on any EGFR TKI. Participants with disease characterized by both MET amplification and EGFR resistance mutations to prior third generation EGFR TKI will be preferentially enrolled into Cohort C. Participants may have received or have been intolerant to prior platinum-based chemotherapy. Cohort MET-2: Participants with documented primary MET Exon 14 skipping mutation non-small cell lung cancer (NSCLC). Cohort E (combination Amivantamab and lazertinib): Participants must have been diagnosed with EGFR Exon 19del or L858R activating mutation and have progressed after first or second-line treatment with a third generation TKI (e.g., osimertinib). Cohort WT-Ad: Participant must have been diagnosed with NSCLC of adenocarcinoma histology, with positive EGFR and/or MET expression as detected on a validated immunohistochemistry (IHC) assay performed by the central laboratory and have progressed on prior platinum containing chemotherapy and PD-1/L1 therapy, either as a combined regimen or as a separate line of therapy. Eligibility may be determined through IHC analysis of either archival (pre-screening) or mandatory fresh tumor tissue collected during the Screening period. Cohort WT-Sq: Participant must have been diagnosed with NSCLC of squamous cell carcinoma histology, with positive EGFR and/or MET expression as detected on a validated IHC assay performed by the central laboratory and have progressed on prior platinum-containing chemotherapy and PD-1/L1 therapy, either as a combined regimen or as a separate line of therapy. Eligibility may be determined through IHC analysis of either archival (pre-screening) or mandatory fresh tumor tissue collected during the Screening
Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria:

Participant has uncontrolled inter-current illness, including but not limited to poorly controlled hypertension, or diabetes, ongoing or active infection, (that is, has discontinued all antibiotics for at least one week prior to first dose of study drug), or psychiatric illness/social situation that would limit compliance with study requirements. Participants with medical conditions requiring chronic continuous oxygen therapy are excluded. For Part 1 Chemotherapy Combination Cohort only: additionally, participants with active bleeding diathesis
Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives whichever is longer, before the first administration of study drug. For agents with long half-lives, the maximum required time since last dose is 4 weeks. Toxicities from previous anti-cancer therapies should have resolved to baseline levels or to Grade 1 or less, (except for alopecia [any grade], Grade less than or equal to [<=] 2 peripheral neuropathy, and Grade less than [<] 2 hypothyroidism stable on hormone replacement). For Part 1 Combination Dose Escalation: Any previous treatment with systemic anti-cancer immunotherapy, including but not limited to anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents. For Part 1 Chemotherapy Combination Cohort only: Any previous treatment with systemic anti-cancer immunotherapy in the past 3 months or localized radiotherapy to lung within the past 6 months. For Part 2 only: Cohorts A and B: Prior treatment with chemotherapy for metastatic disease is not allowed unless the tumor mutation carries de-novo resistance to EGFR TKI (example, Exon 20 insertions). Cohort C and MET-1: Prior treatment with more than 2 lines of cytotoxic chemotherapy for metastatic disease (maintenance therapy is not included). Cohort D: Previous treatment with an EGFR TKI with activity against EGFR Exon 20 insertions (such as poziotinib). Cohort E (combination Amivantamab and lazertinib): Any previous treatment in the metastatic setting with other than a first, second, or third generation EGFR TKI. Cohorts WT-Ad and WT-Sq: more than three lines of prior systemic therapy in the metastatic setting
Participants with untreated brain metastases. Participants with definitively, locally-treated metastases that are clinically stable and asymptomatic for at least 2 weeks and who are off or receiving low-dose corticosteroid treatment (<=10 mg prednisone or equivalent) for at least 2 weeks prior to study treatment are eligible. Exception: participants with asymptomatic, untreated brain metastases, each less than 1 cm in diameter, may be eligible for Amivantamab and lazertinib combination therapy in the Part 1 Combination Dose Escalation or Part 2 Combination Expansion Cohort E
Participant has a history of malignancy other than the disease under study within 3 years before Screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with or minimal risk of recurrence within a year from Screening)
Participant has not fully recovered from major surgery or significant traumatic injury prior the first dose of study drug or expects to have major surgery during the study period or within 6 months after the last dose of study drug
Participant has, or will have, any of the following: a. An invasive operative procedure with entry into a body cavity, within 4 weeks or without complete recovery before Cycle 1 Day 1. Thoracentesis, if needed, and percutaneous biopsy for baseline tumor tissue sample may be done less than 4 weeks prior to Cycle 1 Day 1, as long as the participant has adequately recovered from the procedure prior to the first dose of study drug in the clinical judgement of the investigator; b. Significant traumatic injury within 3 weeks before the start of Cycle 1 Day 1 (all wounds must be fully healed prior to Day 1); c. Any medical condition that requires intact wound healing capacity and is expected to endanger subject safety if wound healing capacity would be severely reduced during administration of the investigational agent; d. Expected major surgery while the investigational agent is being administered or within 6 months after the last dose of study drug

Study is for people with:

Lung Cancer

Phase:

Phase 1

Estimated Enrollment:

780

Study ID:

NCT02609776

Recruitment Status:

Recruiting

Sponsor:

Janssen Research & Development, LLC

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There are 97 Locations for this study

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City of Hope
Duarte California, 91010, United States
UC San Diego Moores Cancer Center
La Jolla California, 92093, United States
Chao Family Comprehensive Cancer Center
Orange California, 92868, United States
UCLA
Santa Monica California, 90404, United States
Samuel Oschin Comprehensive Cancer Center Cedars-Sinai Medical Center
West Hollywood California, 90048, United States
H. Lee Moffitt Cancer & Research Institute
Tampa Florida, 33612, United States
University of Chicago
Chicago Illinois, 60637, United States
Center for Cancer and Blood Disorders
Bethesda Maryland, 20817, United States
Massachusetts General Hospital
Boston Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States
University of Michigan - Rogel Cancer Center
Ann Arbor Michigan, 48109, United States
Barbara Ann Karmanos Cancer Institute
Detroit Michigan, 48201, United States
Mayo Clinic
Rochester Minnesota, 55905, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
Langone Health at NYC University, NYU School of Medicine
New York New York, 10016, United States
Icahn School of Medicine at Mt. Sinai
New York New York, 10029, United States
Columbia University Medical Center
New York New York, 10032, United States
Providence Portland Medical Center
Portland Oregon, 97213, United States
University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Medicine
Philadelphia Pennsylvania, 19104, United States
Sanford Cancer Center - Sanford Hematology Oncology
Sioux Falls South Dakota, 57104, United States
Mary Crowley Medical Research Center
Dallas Texas, 75230, United States
Oncology Consultants - Texas
Houston Texas, 77030, United States
Virginia Cancer Specialists
Fairfax Virginia, 22031, United States
Chris O'Brien Lifehouse
Camperdown , 2050, Australia
Austin Hospital
Heidelberg , 3084, Australia
St George Hospital
Kogarah , 2217, Australia
St John of God Hospital Murdoch
Murdoch , 6150, Australia
Princess Alexandra Hospital
Woolloongabba , 4102, Australia
BC Cancer Agency - Vancouver BC
Vancouver British Columbia, V5Z 4, Canada
University Health Network
Toronto Ontario, M5G 2, Canada
Cancer Hospital Chinese Academy of Medical Sciences
Beijing , 10002, China
Beijing Shijitan Hospital, Capital Medical University
Beijing , 10003, China
Beijing Cancer Hospital
Beijing , 10014, China
Peking University Third Hospital
Beijing , 10019, China
Peking Union Medical College Hospital
Beijing , 10073, China
Jilin cancer hospital
Changchun , 13000, China
The First Bethune Hospital of Jilin University
Changchun , 13002, China
Hunan Cancer hospital
Changsha , 41001, China
Sichuan Cancer Hospital
Chengdu , 61004, China
West China Hospital Sichuan University
Chengdu , 61004, China
Chongqing University Cancer Hospital
Chongqing , 40003, China
Guangdong Provincial People's Hospital
Guangzhou , 51012, China
Zhejiang Cancer Hospital
Hangzhou , 31002, China
Anhui Province Hospital
Hefei , 23000, China
The First Affiliated Hospital of NanChang University
Nanchang , 33005, China
Jiangsu Cancer Hospital
Nanjing , 21000, China
Nantong Tumor Hospital
Nantong , 22600, China
Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
Wuhan , 43003, China
Union Hospital Tongji Medical College of Huazhong University of Science and Technology
Wuhan , 43003, China
The first affiliated hospital of xiamen university
Xiamen , 36100, China
Henan Cancer Hospital
Zhengzhou , 45000, China
Institut Bergonié
Bordeaux , 33000, France
Centre Georges-François Leclerc
Dijon , 21000, France
Centre Leon Bérard
Lyon Cedex 8 , 69373, France
Hopital de la Timone
Marseille , 13885, France
Institut Curie
Paris , 75005, France
Institut de cancerologie de l'ouest
Saint-Herblain Cedex , 44805, France
Institut Gustave Roussy
Villejuif Cedex , 94805, France
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola , 47014, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milano , 20133, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Napoli , 80131, Italy
Ospedale S. Maria Delle Croci
Ravenna , 48121, Italy
National Cancer Center Hospital
Chuo-Ku , 104-0, Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka-city , 811-1, Japan
Hyogo Cancer Center
Hyogo , 673-8, Japan
National Cancer Center Hospital East
Kashiwa , 277-8, Japan
Kurume University Hospital
Kurume , 830-0, Japan
Aichi Cancer Center Hospital
Nagoya-Shi , 464-8, Japan
Niigata Cancer Center Hospital
Niigata , 951-8, Japan
Osaka City General Hospital
Osaka , 534-0, Japan
The Cancer Institute Hospital of JFCR
Tokyo , 135-8, Japan
Wakayama Medical University Hospital
Wakayama , 641-8, Japan
Tottori University Hospital
Yonago , 683-8, Japan
Chungbuk National University Hospital
Cheongju-si , 28644, Korea, Republic of
National Cancer Center
Goyang-si , 10408, Korea, Republic of
Seoul National University Bundang Hospital
Gyeonggi-do , 13620, Korea, Republic of
Gachon University Gil Medical Center
Incheon , 405-7, Korea, Republic of
Seoul National University Hospital
Seoul , 03080, Korea, Republic of
Severance Hospital, Yonsei University Health System
Seoul , 03722, Korea, Republic of
Asan Medical Center
Seoul , 05505, Korea, Republic of
Samsung Medical Center
Seoul , 06351, Korea, Republic of
Hosp. Univ. A Coruña
A Coruña , 15006, Spain
Hosp. de La Santa Creu I Sant Pau
Barcelona , 08025, Spain
Hosp. Univ. Quiron Dexeus
Barcelona , 08028, Spain
Hosp. Univ. Vall D Hebron
Barcelona , 8035, Spain
Hosp. Gral. Univ. Gregorio Marañon
Madrid , 28007, Spain
Hosp. Univ. Ramon Y Cajal
Madrid , 28034, Spain
Hosp. Univ. Fund. Jimenez Diaz
Madrid , 28040, Spain
Hosp. Univ. Hm Sanchinarro
Madrid , 28050, Spain
Hosp. Virgen de La Victoria
Malaga , 29010, Spain
Hosp. Univ. Marques de Valdecilla
Santander , 39008, Spain
Hosp. Virgen Del Rocio
Seville , 41013, Spain
E-DA Hospital
Kaohsiung , 824, Taiwan
Chung Shan Medical University Hospital
Taichung , 403, Taiwan
China Medical University Hospital
Taichung , 40447, Taiwan
Taichung Veterans General Hospital
Taichung , 40705, Taiwan
National Taiwan University Hospital
Taipei City , 10002, Taiwan
Taipei Veterans General Hospital
Taipei , 11217, Taiwan
The Christie Nhs Foundation Trust
Manchester , M20 4, United Kingdom
Sir Bobby Robson Unit, Northern Centre for Cancer Care
Newcastle upon Tyne , NE7 7, United Kingdom
Royal Marsden Hospital
Sutton , SM2 5, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 1

Estimated Enrollment:

780

Study ID:

NCT02609776

Recruitment Status:

Recruiting

Sponsor:


Janssen Research & Development, LLC

How clear is this clinincal trial information?

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