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

Tracking Information

• First Submitted Date: October 6, 2020
• First Posted Date: October 28, 2020
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: November 10, 2020
• Estimated Primary Completion Date: October 8, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 1, 2022)

• 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.
• 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.
• 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.
• Number of Participants with Dose Limiting Toxicity (DLT) [ Time Frame: Up to Day 28 ]
  Number of participants with DLT will be assessed.
• 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.

Original Primary Outcome Measures (submitted: October 22, 2020)

• Observed Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough) [ Time Frame: Up to Day 29 ]
  Ctrough is the observed serum concentration immediately prior to the next drug administration.
• Number of Participants with Adverse Event (AE) [ Time Frame: Up to 3 years and 10 months ]
  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.
• Number of Participants with Dose Limiting Toxicity (DLT) [ Time Frame: Up to Day 28 ]
  Number of participants with DLT will be assessed.
• Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: Up to 3 years and 10 months ]
  Number of participants with clinical laboratory (hematology, clinical chemistry, and urinalysis) abnormalities will be assessed.

Current Secondary Outcome Measures (submitted: January 12, 2022)

• 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.
• 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.
• Epidermal Growth Factor Receptor (EGFR) Concentrations [ Time Frame: Up to 4 years 1 month ]
  EGRF concentrations markers will be assessed.
• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: October 22, 2020)

• Number of Participants with Anti-amivantamab and Anti-rHuPH20 antibodies [ Time Frame: Up to 3 years and 10 months ]
  Number of participants with anti-amivantamab and anti-rHuPH20 antibodies will be assessed.
• Epidermal Growth Factor Receptor (EGFR) Concentrations [ Time Frame: Up to 3 years and 10 months ]
  EGRF concentrations markers will be assessed.
• Mesenchymal-Epidermal Transition Tyrosine Kinase Receptor/Hepatocyte Growth Factor Receptor (cMET) Markers [ Time Frame: Up to 3 years and 10 months ]
  cMET markers will be analyzed.
• Overall Response Rate (ORR) [ Time Frame: Up to 3 years and 10 months ]
  ORR defined as the proportion of participants with partial response (PR) or better according to Response Criteria in Solid Tumors (RECIST) v1.1.
• Maximum Dosing Interval Between Time Zero to Steady State [ Time Frame: Up to 3 years and 10 months ]
  Maximum dosing interval Between time zero to steady state will be assessed.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Malignancies

Intervention

• Drug: Ami-LC-MD
  Participants will receive amivantamab admixed with rHuPH20 SC infusion.
• Drug: Ami-LC
  Participants will receive amivantamab SC infusion.
• 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

Study Arms

• 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.
  Interventions:

  • Drug: Ami-LC-MD
  • Drug: Ami-LC
• 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).
  Interventions:

  • Drug: Ami-HC
  • Drug: Ami-HC-CF
• 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.
  Interventions:

  • Drug: Ami-HC
  • Drug: Ami-HC-CF
  • Drug: Lazertinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 2, 2024): 166
• Original Estimated Enrollment (submitted: October 22, 2020): 80
• Estimated Study Completion Date: October 21, 2025
• Estimated Primary Completion Date: October 8, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Canada, Korea, Republic of, United Kingdom, United States

Administrative Information

• NCT Number: NCT04606381
• Other Study ID Numbers: CR108891; 2020-003225-36 ( EudraCT Number ); 61186372NSC1003 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

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

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024