A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies

Advanced Solid Malignancies Clinical Trial

— PALOMA  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04606381
• Other study ID #: CR108891
• Secondary ID: 2020-003225-3661
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 10, 2020
• Est. completion date: October 21, 2025

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: October 21, 2025
• Est. primary completion date: July 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Malignancies
• Neoplasms

Intervention

Drug:
• Ami-LC-MD
Participants will receive amivantamab admixed with rHuPH20 SC infusion.
• Ami-LC
Participants will receive amivantamab SC infusion.
• Ami-HC
Participants will receive amivantamab SC infusion.
• Ami-HC-CF
Participants will receive amivantamab co-formulated with rHuPH20 as SC infusion.
• Lazertinib
Participants will receive lazertinib orally as a film-coated tablet.

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
United Kingdom	The Christie Nhs Foundation Trust	Manchester
United Kingdom	Royal Marsden Hospital	Sutton
United States	Community Health Network	Indianapolis	Indiana
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Langone Health at NYC University, NYU School of Medicine	New York	New York
United States	Providence Portland Medical Center	Portland	Oregon
United States	Cedars Sinai Medical Center	West Hollywood	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Observed Amivantamab Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough)	Ctrough is the observed amivantamab serum concentration immediately prior to the next drug administration.	Up to Day 29
Primary	Amivantamab Steady-state Area Under the Curve (AUCss)	AUCss is defined as the area under the curve for amivantamab at steady state.	Cycle 4 (28 days)
Primary	Number of Participants with Adverse Event (AE)	An adverse event is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the drug. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.	Up to 4 years 1 month
Primary	Number of Participants with Dose Limiting Toxicity (DLT)	Number of participants with DLT will be assessed.	Up to Day 28
Primary	Number of Participants with Clinical Laboratory Abnormalities	Number of participants with clinical laboratory (hematology, clinical chemistry, and urinalysis) abnormalities will be assessed.	Up to 4 years 1 month
Secondary	Number of Participants with Anti-amivantamab and Anti-rHuPH20 antibodies	Number of participants with anti-amivantamab and anti-rHuPH20 antibodies will be assessed.	Up to 4 years 1 month
Secondary	Part 3: Plasma Concentration of Lazertinib	Plasma samples will be analyzed to determine concentrations of lazertinib using a validated method.	Up to 4 years 1 month
Secondary	Epidermal Growth Factor Receptor (EGFR) Concentrations	EGRF concentrations markers will be assessed.	Up to 4 years 1 month
Secondary	Mesenchymal-Epidermal Transition Tyrosine Kinase Receptor/Hepatocyte Growth Factor Receptor (cMET) Markers	cMET markers will be analyzed.	Up to 4 years 1 month
Secondary	Overall Response Rate (ORR)	ORR defined as the proportion of participants with partial response (PR) or better according to Response Criteria in Solid Tumors (RECIST) v1.1.	Up to 4 years 1 month
Secondary	Part 2: Maximum Amivantamab Dosing Interval Between Time Zero to Steady State	Maximum amivantamab dosing interval Between time zero to steady state will be assessed.	Up to 4 years 1 month