amivantamab SC (Ami-LC) / J&J, Halozyme - LARVOL DELTA

PALOMA-2: A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=390 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Oct 2025 ➔ Aug 2027

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

OrigAMI-2: A randomized, phase 3 study of amivantamab vs cetuximab, both in combination with FOLFOX or FOLFIRI, as first-line treatment in left-sided RAS/BRAF wild-type metastatic colorectal cancer. (ASCO 2025) - P1/2, P3 | "Approximately 1000 participants will be randomly assigned 1:1 to receive subcutaneous amivantamab (co-formulated with recombinant human hyaluronidase [rHuPH20]) or intravenous cetuximab, both combined with FOLFOX or FOLFIRI (investigator's choice)...Secondary endpoints include overall survival, objective response rate, duration of response, and patient-reported outcomes. Safety assessments will include monitoring adverse events and laboratory abnormalities."

Clinical • Combination therapy • Metastases • P3 data • Colorectal Cancer • Lung Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • MET • MSI • NRAS • RAS

OrigAMI-3: A randomized, phase 3 study of amivantamab plus FOLFIRI vs cetuximab or bevacizumab plus FOLFIRI in participants with recurrent, unresectable, or metastatic RAS/BRAF wild-type colorectal cancer. (ASCO 2025) - P1/2, P3 | "Eligible pts will be WT for KRAS, NRAS, and BRAF, have recurrent unresectable or mCRC, and must have had disease progression on one prior line of systemic therapy for metastatic disease (prior regimen must be fluoropyrimidine-based and oxaliplatin-based therapy)...Approximately 700 pts will be randomly assigned 1:1 to receive subcutaneous amivantamab (co-formulated with recombinant human hyaluronidase [rHuPH20]) plus FOLFIRI vs intravenous cetuximab or bevacizumab (investigator's choice, per local guidelines) plus FOLFIRI...Secondary endpoints include objective response rate, duration of response, and patient-reported outcomes. Safety assessments will include monitoring adverse events and laboratory abnormalities."

Clinical • IO biomarker • Metastases • P3 data • Colorectal Cancer • Lung Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • MET • MSI • NRAS • RAS

COCOON: Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Recruiting | N=201 ➔ 300

Adverse events • Enrollment change • Enrollment open • Dermatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

PALOMA-2: A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=390 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Aug 2026 ➔ Aug 2027

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A phase 2b study of subcutaneous amivantamab with lazertinib as first-line treatment, or with chemotherapy as second-line treatment, for EGFR-mutated non-small cell lung cancer (NSCLC): COPERNICUS (AACR 2025) - P2 | "In Cohort 1, participants must not have received any prior systemic therapy and will receive SC amivantamab and oral lazertinib; in Cohort 2, participants must have had disease progression after EGFR-TKI monotherapy and will receive SC amivantamab and chemotherapy (carboplatin-pemetrexed). COPERNICUS aims to evaluate the efficacy and safety of SC amivantamab regimens using a pragmatic study design to enroll participants with diverse backgrounds and combine advancements in supportive care to prevent and proactively manage AEs."

Clinical • P2b data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

European Commission approves subcutaneous RYBREVANT (amivantamab) for the treatment of patients with advanced EGFR-mutated non-small cell lung cancer (GlobeNewswire) - "Janssen-Cilag International NV...today announced that the European Commission (EC) has approved an extension of marketing authorisation for a subcutaneous (SC) formulation of RYBREVANT(amivantamab), in combination with LAZCLUZE (lazertinib) for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy. For these indications, it is recommended that SC amivantamab is administered weekly from Weeks 1 to 4 (total of four doses), then every two weeks starting at Week 5 onwards....The EC approval is supported by positive results from the Phase 3 PALOMA-3 study..."

EGFR exon 20 • EMA approval • Evidence highlight • Non Small Cell Lung Cancer • EGFR

COCOON: Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Janssen Research & Development, LLC | N=200 ➔ 300

Enrollment change • Dermatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

COCOON: Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib (clinicaltrials.gov) - P2 | N=201 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | N=300 ➔ 201 | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment change • Enrollment closed • Dermatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

COCOON: Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Recruiting

Adverse events • Enrollment open • Dermatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

COCOON: Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib (clinicaltrials.gov) - P2 | N=201 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed • Dermatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

COCOON: Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Jul 2025 ➔ Nov 2025

Adverse events • Trial primary completion date • Dermatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

ORIC-114 in Combination with Subcutaneous Amivantamab in Patients with EGFR Exon20 Insertion Mutant NSCLC (clinicaltrials.gov) - P1 | N=76 | Recruiting | Sponsor: ORIC Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ORIC-114 in Combination with Subcutaneous Amivantamab in Patients with EGFR Exon20 Insertion Mutant NSCLC (clinicaltrials.gov) - P1 | N=76 | Not yet recruiting | Sponsor: ORIC Pharmaceuticals

New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

CHMP recommends subcutaneous RYBREVANT (amivantamab) for the treatment of patients with advanced EGFR-mutated non-small cell lung cancer (GlobeNewswire) - "Janssen-Cilag International NV...announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended an extension of marketing authorisation for a subcutaneous (SC) formulation of RYBREVANT(amivantamab), in combination with LAZCLUZE (lazertinib) for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy. For these indications, it is recommended that SC amivantamab is administered weekly from Weeks 1 to 4 (total of four doses), then every two weeks starting at Week 5 onwards...The CHMP positive opinion is supported by positive results from the Phase 3 PALOMA-3 study..."

CHMP • EGFR exon 20 • Non Small Cell Lung Cancer

LUNG-MAP SUB-STUDY: Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has Increased Copies of the MET Gene (An Expanded Lung-MAP Treatment Trial) (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: SWOG Cancer Research Network | Trial completion date: May 2029 ➔ May 2028

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • HER-2 • KRAS • MET • NTRK • RET • ROS1

Prevention and Treatment of Venous Thromboembolism Associated with Amivantamab-Based Therapies in Patients with Lung Cancer-Provisional Clinical Opinion Based on Existing Clinical Practice Guidelines. (PubMed, Cancers (Basel)) - "However, a high risk of venous thromboembolism (VTE) was observed in patients treated with amivantamab-based therapies, with considerable differences in VTE risk according to the line of systemic treatment, concomitant treatment with lazertinib, and intravenous vs. subcutaneous amivantamab administration. However, open questions remain concerning the type, dosing, and duration of primary pharmacological thromboprophylaxis in patients treated with amivantamab-based therapies. Therefore, the aim of this clinical opinion piece is to provide provisional guidance on how to mitigate VTE risk in patients treated with amivantamab-based therapies following existing clinical practice guidelines on primary thromboprophylaxis and treatment of VTE in ambulatory patients with cancer."

Clinical guideline • Journal • Cardiovascular • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Venous Thromboembolism • EGFR

Amivantamab SC: Regulatory approval in US/EU for NSCLC (based on PALOMA-3 trial) in 2025 (J&J) - Q4 2024 Results

EMA approval • FDA approval • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Update on U.S. regulatory review of subcutaneous amivantamab (J&J Press Release) - "Johnson & Johnson...announced the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) for a fixed combination of amivantamab and recombinant human hyaluronidase for subcutaneous administration (SC amivantamab) in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The CRL is related to observations as part of a standard pre-approval inspection at a manufacturing facility. The CRL is unrelated to the product formulation, or the efficacy and safety data submitted in the regulatory application, and the FDA has not requested any additional clinical studies. The currently approved intravenous (IV) formulation of RYBREVANT (amivantamab-vmjw) is not impacted by the CRL....The BLA is based on the Phase 3 PALOMA-3 study results presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology."

CRL • Non Small Cell Lung Cancer

Leclaza + Rybrevant SC, improved infusion reactions and thrombosis in Asian patients as well [Google translation] (HIT News) - P3 | N=418 | PALOMA-3 (NCT05388669) | Sponsor: Janssen Research & Development, LLC | "In the Asian subgroup analysis of the phase 3 clinical trial 'PALOMA-3' study comparing the subcutaneous (SC) and intravenous (IV) formulations of 'Leclaza (ingredient: lazertinib)' and 'Rybrevant (ingredient: amivantamab)' for EGFR mutant non-small cell lung cancer, the benefits of improving infusion-related reactions (IRR) and venous thromboembolism (VTE) were also proven....PFS did not reach the median in the Rybrevant SC combination group, but it was 5.6 months in the IV group (HR 0.84, p=0.35). However, Professor Lee Se-hoon explained that there is a trend toward improvement. At 12 months, 77% of patients in the SC arm and 61% of patients in the IV arm were alive, but the median overall survival (OS) was not reached in either group (HR 0.60, 95% CI: 0.33-10.8)."

P3 data • Non Small Cell Lung Cancer

Taking on Acquired Resistance in EGFR-Mutant NSCLC - TKIs are the first-line of defense, but "the more options we have the better," expert says (MedPageToday) - "Velcheti said that more data are needed to fully understand when to continue targeting EGFR and when to switch to other classes of drugs. To that end, the phase II ORCHARD trialopens in a new tab or window will test different agents in combination with osimertinib based on the identified TKI resistance mechanisms. These other agentsopens in a new tab or window include savolitinib, gefitinib (Iressa), Dato-DXd, necitumumab (Portrazza), and other drugs specific to MET alterations, C797X mutations, or no identified biomarker."

Media quote

COPERNICUS: A Study of Amivantamab in Combination With Lazertinib, or Amivantamab in Combination With Platinum-Based Chemotherapy, for Common Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=365 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

COPERNICUS: A Study of Amivantamab in Combination With Lazertinib, or Amivantamab in Combination With Platinum-Based Chemotherapy, for Common Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=365 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

Combination therapy • Metastases • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

PALOMA-3: A Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=418 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jan 2025 ➔ Dec 2025

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

The Targeted Pulse: NKT2152 Sparks Excitement in RCC, Amivantamab/Chemotherapy Combo Receives Approval for EGFR-Mutant NSCLC, and More (Targeted Oncology) - "'NKT2152 demonstrated robust antitumor activity in heavily pretreated patients with high-risk advanced clear cell RCC,' said Eric Jonasch, MD..."

Video • Renal Cell Carcinoma