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

Amivantamab in recurrent/metastatic head & neck squamous cell cancer (HNSCC) after disease progression on checkpoint inhibition and chemotherapy: Results from the phase 1b/2 OrigAMI-4 study (JADPRO 2025) - "Subcutaneous amivantamab plus pembrolizumab and carboplatin is proceeding to first-line, phase 3 development in the OrigAMI-5 trial. Background Cetuximab monotherapy demonstrated response rates of up to 24% among participants with human papillomavirus (HPV)-unrelated R/M HNSCC after disease progression on checkpoint inhibitor and platinum-based chemotherapy...Figure 3: Rapid antitumor activity (CT scans showing reduction in tumor mass at week 7). Figure 4: Durability of response – 46% remained on treatment at data cut-off."

Checkpoint inhibition • IO biomarker • Metastases • P1/2 data • Dental Disorders • Fatigue • Head and Neck Cancer • Hypopharyngeal Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Stomatitis

COPERNICUS: A multinational pragmatic phase II trial of subcutaneous (SC) amivantamab (Ami) in common EGFR-mutated (cEGFRm) NSCLC (ESMO 2025) - P2 | "Background In advanced c EGFR m (exon 19 deletion/exon 21 L858R substitution) NSCLC, intravenous (IV) ami is FDA-/EMA-approved combined with lazertinib (laz) for first-line (1L), and with carboplatin-pemetrexed (chemo) for second-line (2L) treatment. Legal entity responsible for the study Johnson & Johnson. Funding Johnson & Johnson."

P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Subcutaneous (SC) amivantamab (ami) plus chemotherapy (chemo) in EGFR-mutant (EGFRm) advanced non-small cell lung cancer (NSCLC) after disease progression on osimertinib (osi) (ESMO 2025) - P2 | "Carboplatin was given up to 4 cycles, and pemetrexed until disease progression. Ami discontinuation due to treatment-related AEs was 5%. Conclusions In pts with EGFR m advanced NSCLC post-osi, ami SC Q3W + chemo had a response rate and safety profile consistent with historical ami IV Q3W + chemo, with fewer ARRs."

Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Amivantamab in recurrent/metastatic head & neck squamous cell cancer (HNSCC) after disease progression on checkpoint inhibition and chemotherapy: Results from the phase Ib/II OrigAMI-4 study (ESMO 2025) - P1/2 | "Conclusions Amivantamab demonstrated rapid and meaningful antitumor activity in pts with HPV-unrelated, previously treated R/M HNSCC after disease progression on checkpoint inhibition and chemotherapy. The early safety profile was consistent with prior studies, with no new safety signals identified."

Checkpoint inhibition • IO biomarker • Metastases • P1/2 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Amivantamab plus paclitaxel in recurrent/metastatic (R/M) head & neck squamous cell cancer (HNSCC) after disease progression on checkpoint inhibition: Identification of the recommended combination dose from the phase Ib/II OrigAMI-4 study (ESMO 2025) - P1/2 | "Conclusions Ami + paclitaxel was shown to be safe, with no new safety signals identified. The combination showed rapid and meaningful antitumor activity in pts with HPV-unrelated, previously treated R/M HNSCC after disease progression on checkpoint inhibition."

Checkpoint inhibition • IO biomarker • Metastases • P1/2 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Subcutaneous (SC) after intravenous (IV) amivantamab in advanced NSCLC: Initial results from PALOMA-2 (JADPRO 2025) - P1/2 | "The safety profile of participants who switched to amivantamab SC with lazertinib from IV AMV to SC AMV therapy was consistent with the profile previously observed with AMV SC monotherapy, demonstrating that the IV to SC switch occurred safely. Most participants were satisfied with AMV SC with or without rHuPH20, found it convenient, and preferred it over prior intravenous IV AMV."

Metastases • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

PALOMA-2: Initial Report Details Patient Experiences of Subcutaneous Amivantamab After IV Administration in Advanced EGFR-Mutated NSCLC (Cancer Nursing Today) - "The median duration of treatment was 3.1 months for IV administration and 7.4 months for subcutaneous administration. The median follow-up from the first subcutaneous dose was 9.7 months....In addition, most adverse events were graded between 1 and 2, and the most common adverse events included paronychia (44%), rash (40%), and hypoalbuminemia (40%). Only one patient discontinued treatment due to the toxicity of interstitial lung disease."

P2 data • Non Small Cell Lung Cancer

Subcutaneous amivantamab delivers promising 45 percent overall response rate with median duration of 7.2 months in recurrent or metastatic head and neck cancer (PRNewswire) - "Data were presented during a mini-oral session at the European Society for Medical Oncology (ESMO) 2025 Congress....In Cohort 1 of the OrigAMI-4 study, treatment with SC amivantamab resulted in an overall response rate (the primary endpoint) of 45 percent in 38 efficacy-evaluable patients with R/M HNSCC unrelated to HPV with disease progression on or after a PD-1 or PD-L1 checkpoint inhibitor and platinum-based chemotherapy (95 percent confidence interval [CI], 29-62)....Median progression-free survival was 6.8 months (95 percent CI, 4.2-9.0)....Based on these results, Johnson & Johnson is initiating further study of SC amivantamab in head and neck cancer with the Phase 3 OrigAMI-5 study..."

New P3 trial • P1/2 data • Squamous Cell Carcinoma of Head and Neck

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=520 | Recruiting | Sponsor: Janssen Research & Development, LLC | N=390 ➔ 520

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

The Phase 2b COPERNICUS 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: a Vodcast. (PubMed, Oncol Ther) - P2 | "COPERNICUS uses a pragmatic study design to evaluate the efficacy and safety of subcutaneous amivantamab regimens combined with advancements in supportive care to prevent and proactively manage AEs in a diverse participant population. Supplementary file1 (MP4 117333 KB)."

Journal • P2b data • Cardiovascular • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Venous Thromboembolism • EGFR

PALOMA-2: Subcutaneous Amivantamab Administered Every 4 Weeks Plus Lazertinib in First-Line EGFR-Mutated Advanced NSCLC (IASLC-WCLC 2025) - P2 | "In MARIPOSA (median follow-up, 22.0 months), intravenous amivantamab administered every 2 weeks (Q2W) plus lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib (hazard ratio, 0.70; P <0.001). Conclusions : In participants with EGFR- mutated advanced NSCLC, first-line treatment with subcutaneous amivantamab Q4W plus lazertinib showed a response rate similar to historical intravenous amivantamab Q2W data with fewer ARRs; incidence of VTEs was low with prophylactic anticoagulation. The subcutaneous amivantamab Q4W regimen will potentially further improve patient convenience and overall treatment experience."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

First-Line Subcutaneous Amivantamab Plus Chemotherapy in EGFR Exon 20 Insertion-Mutated Advanced NSCLC: Results From PALOMA-2 (IASLC-WCLC 2025) - P2 | "Introduction : Intravenous amivantamab plus chemotherapy (carboplatin-pemetrexed)is approved for first-line treatment of patients with EGFR exon 20 insertion(Ex20ins)-mutated advanced non-small cell lung cancer (NSCLC), based on the resultsof the PAPILLON study. Discontinuationof amivantamab due to treatment-related AEs was 12%. Conclusions : Among participants with EGFR Ex20ins-mutatedadvanced NSCLC, first-line treatment with subcutaneous amivantamab Q3W plus chemotherapydemonstrated a response rate and safety profile consistent with historical intravenousamivantamab Q3W data, with a reduced incidence of ARRs."

Clinical • EGFR exon 20 • Metastases • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Solid Tumor • EGFR

PALOMA: A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (clinicaltrials.gov) - P1 | N=192 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Apr 2027 ➔ Dec 2026

Trial completion date • Breast Cancer • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thyroid Gland Carcinoma • MET

New data…will be presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC) (J&J Press Release) - "Highlights include:...(i) Results from the Phase 2 PALOMA-2 study including an evaluation of once-monthly subcutaneous amivantamab combined with LAZCLUZE as a first-line treatment for EGFR-mutated lung cancer, as well as subcutaneous amivantamab plus chemotherapy in patients in the second-line setting after prior treatment with the combination in the first line (Mini Oral Abstract MA08.05); (ii) Findings from the Phase 2 PALOMA-2 study evaluating subcutaneous amivantamab plus chemotherapy as a first-line treatment in patients with NSCLC with EGFR exon 20 insertion mutations (Mini Oral Abstract MA08.03)."

EGFR exon 20 • P2 data • Non Small Cell Lung Cancer

PALOMA-2 Trial Supports SC Amivantamab Q4W as a Patient-Centered Alternative to IV Therapy (AJMC) - "indings from cohort 5, which specifically assessed the Q4W dosing schedule of PALOMA-2, were presented at the 2025 World Conference on Lung Cancer...The Q4W regimen demonstrated high efficacy, with an ORR of 82% (95% CI, 71%-90%) by the investigator and 87% (95% CI, 77%-94%) by ICR. The confirmed ORRs were 79% and 83%, respectively. Median time to response was 8.1 weeks (range, 7.0-16.5), consistent with expectations for targeted therapy in this population....At 6.5 months of follow-up, 87% of participants remained on study treatment, indicating strong ongoing disease control."

P2 data • Non Small Cell Lung Cancer

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 | Trial completion date: Mar 2026 ➔ Jan 2032 | Trial primary completion date: Nov 2025 ➔ May 2027

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

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: Dec 2025 ➔ Jun 2026

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

Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated non-small cell lung cancer: Patient satisfaction and resource utilization results from the PALOMA-3 study. (PubMed, Eur J Cancer) - "In PALOMA-3, subcutaneous amivantamab, which simplifies and shortens administration, reduces resource utilization, and enhances treatment experience, was a preferred option for patients who received amivantamab-lazertinib."

HEOR • Journal • Cardiovascular • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • Venous Thromboembolism • EGFR

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=480 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jun 2029 ➔ Nov 2030

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

CAPT-HN: Combined Amivantamab, Carboplatin and Paclitaxel in Unresectable Locally Recurrent or Metastatic Head and Neck Cancer (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: SWOG Cancer Research Network

New P2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

PALOMA: A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (clinicaltrials.gov) - P1 | N=192 | Recruiting | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Recruiting | Trial completion date: Oct 2025 ➔ Apr 2027

Enrollment open • Trial completion date • Breast Cancer • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thyroid Gland Carcinoma • MET

PALOMA: A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (clinicaltrials.gov) - P1 | N=192 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thyroid Gland Carcinoma • MET

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

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

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