Clinical trial NCT04606381: A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies
Official title: An Open-label, Multicenter, Dose Escalation Phase 1b Study to Assess the Safety and Pharmacokinetics of Subcutaneous Delivery of Amivantamab, a Human Bispecific EGFR and cMet Antibody for the Treatment of Advanced Solid Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Malignancies
Keywords: Amivantamab
JNJ-61186372
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-10-28
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the feasibility of subcutaneous (SC) administration of amivantamab based on safety and pharmacokinetics and determine a dose, dose regimen and formulation for amivantamab SC delivery.


Eligibility criteria: Inclusion criteria:

* Part 1 and Part 2: Participant must have histologically or cytologically confirmed solid malignancy that is metastatic or unresectable and which may derive benefit from epidermal growth factor receptor (EGFR) or mesenchymal-epidermal transition tyrosine kinase receptor/hepatocyte growth factor receptor (cMet) directed therapy. Eligible tumor types include non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), hepatocellular cancer (HCC), colorectal cancer (CRC), renal cell cancer (RCC), medullary thyroid cancer (MTC), gastroesophageal cancer (GEC), mesothelioma, breast cancer (BC) and ovarian cancer (OC). Participants must have either progressed after prior standard of care therapy for metastatic disease, 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; Part 3: Participants with histologically or cytologically confirmed NSCLC with previously identified EGFR mutation (identified locally in a Clinical Laboratory Improvement Amendments \[CLIA\]-certified laboratory \[or equivalent\]) that is metastatic or unresectable and have progressed on or after at least one line of standard of care systemic treatment for metastatic disease. Required prior therapy includes an approved anti-EGFR tyrosine kinase inhibitor (TKI), or in the case of EGFR exon 20 insertion mutation disease, platinum-based chemotherapy. A participant who has refused all other currently available therapeutic options is allowed to enroll and must be documented in the study records
* Participant must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) at Screening and a negative urine or serum pregnancy test within 24 hours before the first dose of study drug
* A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study drug
* A man who is sexually active with a woman of childbearing potential must agree to use a condom and his partner must also be practicing a highly effective method of contraception (that is, established use of oral, injected or implanted hormonal methods of contraception; placement of an Intrauterine device \[IUD\] or Intrauterine system \[IUS\])

Exclusion criteria:

* Participant has uncontrolled inter-current illness, including but not limited to poorly controlled hypertension or diabetes, ongoing or active systemic infection (that is, has discontinued all antibiotics for at least one week prior to first dose of study drug), diagnosed or suspected viral infection (except Human immunodeficiency virus \[HIV\] positive participants with 1 or more of the following: a) not receiving highly active antiretroviral therapy; b) a change in antiretroviral therapy within 6 months of the start of screening; c) cluster of differentiation 4 (CD4)+ T-cell count less than \[\<\]350 per cubic millimeters \[mm\^3\] at screening; d) an acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening), or psychiatric illness/social situation that would limit compliance with study requirements, including ability to self-care for anticipated toxicities \[that is. rash or paronychia\]. Participants with medical conditions requiring chronic continuous oxygen therapy are excluded
* Participant has had prior chemotherapy, targeted cancer therapy, or treatment with an investigational anti-cancer agent within 2 weeks or 4 half-lives, whichever is longer, before the first administration of study drug; or participant has received prior immunotherapy within 6 weeks 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 anticancer 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). Autoimmune toxicities from previous immunotherapy must be fully resolved to baseline levels
* Participants with untreated brain metastases. Participants with 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 milligrams \[mg\] prednisone or equivalent) for at least 2 weeks prior to study treatment are eligible
* Participant has an active malignancy other than the disease under study requiring treatment
* Participant has leptomeningeal disease

Primary outcomes:
measure: Observed Amivantamab Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough)
timeFrame: Up to Day 29
measure: Amivantamab Steady-state Area Under the Curve (AUCss)
timeFrame: Cycle 4 (28 days)
measure: Number of Participants with Adverse Event (AE)
timeFrame: Up to 4 years 1 month
measure: Number of Participants with Dose Limiting Toxicity (DLT)
timeFrame: Up to Day 28
measure: Number of Participants with Clinical Laboratory Abnormalities
timeFrame: Up to 4 years 1 month
Secondary outcomes:
measure: Number of Participants with Anti-amivantamab and Anti-rHuPH20 antibodies
timeFrame: Up to 4 years 1 month
measure: Part 3: Plasma Concentration of Lazertinib
timeFrame: Up to 4 years 1 month
measure: Epidermal Growth Factor Receptor (EGFR) Concentrations
timeFrame: Up to 4 years 1 month
measure: Mesenchymal-Epidermal Transition Tyrosine Kinase Receptor/Hepatocyte Growth Factor Receptor (cMET) Markers
timeFrame: Up to 4 years 1 month
measure: Overall Response Rate (ORR)
timeFrame: Up to 4 years 1 month
measure: Part 2: Maximum Amivantamab Dosing Interval Between Time Zero to Steady State
timeFrame: Up to 4 years 1 month
Other outcomes:
Locations:
city: West Hollywood
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: New York
country: United States
facility: Langone Health at NYC University, NYU School of Medicine
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: