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

• ClinicalTrials.gov Identifier: NCT04606381
• Recruitment Status: Recruiting
• First Posted: October 28, 2020
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Malignancies	Drug: Ami-LC-MD; Drug: Ami-LC; Drug: Ami-HC; Drug: Ami-HC-CF; Drug: Lazertinib	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 166 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 10, 2020
• Estimated Primary Completion Date: October 8, 2024
• Estimated Study Completion Date: October 21, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1: Ami-LC-MD and Ami-LC; Participants in cohort 1a will receive amivantamab admixed with rHuPH20 (Ami-LC-MD) subcutaneous (SC) infusion and participants in cohort 1b will receive amivantamab (Ami-LC) SC infusion.	Drug: Ami-LC-MD; Participants will receive amivantamab admixed with rHuPH20 SC infusion.; Drug: Ami-LC; Participants will receive amivantamab SC infusion.
Experimental: Part 2: Ami-HC and Ami-HC-CF; Participants will receive SC infusion of newly developed high concentration amivantamab (Ami-HC) or amivantamab co-formulated with rHuPH20 (Ami-HC-CF).	Drug: Ami-HC; Participants will receive amivantamab SC infusion.; Drug: Ami-HC-CF; Participants will receive amivantamab co-formulated with rHuPH20 as SC infusion.
Experimental: Part 3: Ami-HC-CF + Lazertinib and Ami-HC+ Lazertinib; Participants will receive SC infusion of either Ami-HC-CF or Ami-HC in combination with lazertinib tablet.	Drug: Ami-HC; Participants will receive amivantamab SC infusion.; Drug: Ami-HC-CF; Participants will receive amivantamab co-formulated with rHuPH20 as SC infusion.; Drug: Lazertinib; Participants will receive lazertinib orally as a film-coated tablet.; Other Names: JNJ-73841937; YH25448

Outcome Measures

Primary Outcome Measures :

1. Observed Amivantamab Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough) [ Time Frame: Up to Day 29 ]
   Ctrough is the observed amivantamab serum concentration immediately prior to the next drug administration.
2. Amivantamab Steady-state Area Under the Curve (AUCss) [ Time Frame: Cycle 4 (28 days) ]
   AUCss is defined as the area under the curve for amivantamab at steady state.
3. Number of Participants with Adverse Event (AE) [ Time Frame: Up to 4 years 1 month ]
   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.
4. Number of Participants with Dose Limiting Toxicity (DLT) [ Time Frame: Up to Day 28 ]
   Number of participants with DLT will be assessed.
5. Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: Up to 4 years 1 month ]
   Number of participants with clinical laboratory (hematology, clinical chemistry, and urinalysis) abnormalities will be assessed.

Secondary Outcome Measures :

1. Number of Participants with Anti-amivantamab and Anti-rHuPH20 antibodies [ Time Frame: Up to 4 years 1 month ]
   Number of participants with anti-amivantamab and anti-rHuPH20 antibodies will be assessed.
2. Part 3: Plasma Concentration of Lazertinib [ Time Frame: Up to 4 years 1 month ]
   Plasma samples will be analyzed to determine concentrations of lazertinib using a validated method.
3. Epidermal Growth Factor Receptor (EGFR) Concentrations [ Time Frame: Up to 4 years 1 month ]
   EGRF concentrations markers will be assessed.
4. Mesenchymal-Epidermal Transition Tyrosine Kinase Receptor/Hepatocyte Growth Factor Receptor (cMET) Markers [ Time Frame: Up to 4 years 1 month ]
   cMET markers will be analyzed.
5. Overall Response Rate (ORR) [ Time Frame: Up to 4 years 1 month ]
   ORR defined as the proportion of participants with partial response (PR) or better according to Response Criteria in Solid Tumors (RECIST) v1.1.
6. Part 2: Maximum Amivantamab Dosing Interval Between Time Zero to Steady State [ Time Frame: Up to 4 years 1 month ]
   Maximum amivantamab dosing interval Between time zero to steady state will be assessed.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

Locations

United States, California

Cedars Sinai Medical Center; Recruiting

West Hollywood, California, United States, 90048

United States, Indiana

Community Health Network; Recruiting

Indianapolis, Indiana, United States, 46256

United States, New York

Langone Health at NYC University, NYU School of Medicine; Recruiting

New York, New York, United States, 10016

United States, Oregon

Providence Portland Medical Center; Recruiting

Portland, Oregon, United States, 97213

United States, Tennessee

Sarah Cannon Research Institute; Recruiting

Nashville, Tennessee, United States, 37203

Canada, Ontario

University Health Network; Recruiting

Toronto, Ontario, Canada, M5G 2M9

Korea, Republic of

Chungbuk National University Hospital; Recruiting

Cheongju-si, Korea, Republic of, 28644

Seoul National University Bundang Hospital; Recruiting

Seongnam-si, Korea, Republic of, 13620

Severance Hospital Yonsei University Health System; Recruiting

Seoul, Korea, Republic of, 03722

Samsung Medical Center; Recruiting

Seoul, Korea, Republic of, 06351

United Kingdom

The Christie Nhs Foundation Trust; Active, not recruiting

Manchester, United Kingdom, M20 4BX

Royal Marsden Hospital; Recruiting

Sutton, United Kingdom, SM2 5PT

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT04606381
• Other Study ID Numbers: CR108891; 2020-003225-36 ( EudraCT Number ); 61186372NSC1003 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: October 28, 2020
• Last Update Posted: April 24, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:

Amivantamab; JNJ-61186372

Additional relevant MeSH terms:

Neoplasms; Lazertinib; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action