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

Trial Status: Active

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).

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 (Cohort C and hepatocyte growth factor receptor gene [MET]-1: epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKI]; Cohort D and MET-2: platinum-based chemotherapy) 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 (eg, 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 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 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 (exampe, 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 (eg, osimertinib)
  • 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
  • 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

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE
Contact: Lia Etheridge
Phone: 310-825-7174
Orange
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: ACTIVE
Contact: Thanh Phan
Phone: 714-456-5723
Email: tphan@uci.edu
San Diego
University of California San Diego
Status: ACTIVE

Florida

Tampa
Moffitt Cancer Center
Status: ACTIVE
Contact: Eric B. Haura
Phone: 800-456-7121

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: ACTIVE

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE
Massachusetts General Hospital Cancer Center
Status: ACTIVE

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: ACTIVE

Minnesota

Rochester
Mayo Clinic in Rochester
Status: ACTIVE

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE

New York

New York
Icahn School of Medicine at Mount Sinai
Status: ACTIVE
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: ACTIVE
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: ACTIVE

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.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Janssen Pharmaceuticals

  • Primary ID CR108064
  • Secondary IDs NCI-2018-00140, 2018-003908-38, 61186372EDI1001
  • Clinicaltrials.gov ID NCT02609776