Rybrevant (amivantamab-vmjw) / Genmab, J&J - LARVOL DELTA

Treatment With Amivantamab and Hyaluronidase or Cetuximab for Advanced Skin Cancer in People With a Weakened Immune System (clinicaltrials.gov) - P2 | N=86 | Recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Oct 2026 ➔ Mar 2026

Trial initiation date • Genetic Disorders • Multiple Myeloma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • mTOR

ALK101sc, a novel afucosylated bispecific antibody targeting EGFR and c-MET with common light chain demonstrates potent, broad-spectrum antitumor activity (AACR 2026) - "Furthermore, combining ALK101sc with osimertinib produced synergistic antitumor efficacy, even in the presence of TKI‑insensitive mutations...Moreover, its CLC-based design provides a streamlined CMC development pathway, positioning it as a promising therapeutic candidate for overcoming EGFR TKI resistance. Compared with intravenous formulations, subcutaneous ALK101sc can substantially reduce administration time, improve patient convenience, and is expected to have a more favorable safety profile—characterized by meaningful reductions in infusion‑related reactions (IRR) and venous thromboembolism (VTE) rates."

Bispecific • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • EGFR • HGF • MET

Zipalertinib in Patients With EGFR Exon 20 Insertion-Positive NSCLC Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab. (PubMed, J Clin Oncol) - P1/2 | "Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with EGFR ex20ins-mutant NSCLC who received prior platinum-based chemotherapy with or without amivantamab."

Journal • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • EGFR

Lazertinib Versus Osimertinib in Previously Untreated EGFR-mutant Advanced NSCLC: A Randomized, Double-blind, Exploratory Analysis From MARIPOSA. (PubMed, J Thorac Oncol) - "Lazertinib showed comparable efficacy and safety to osimertinib, including in predefined subgroups."

Clinical • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Enhanced Versus Standard Dermatologic Management With Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC: The COCOON Global Randomized Controlled Trial. (PubMed, J Thorac Oncol) - P2 | "An uncomplicated, widely available, prophylactic regimen (COCOON DM) reduced the incidence of DAEIs with amivantamab-lazertinib and the impact of symptoms on QoL."

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

Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non-Small Cell Lung Cancer: Results From CHRYSALIS-2. (PubMed, J Clin Oncol) - "In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals."

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

Overall survival for amivantamab plus lazertinib vs osimertinib in Asian participants with first-line EGFR-mutant advanced NSCLC: MARIPOSA subgroup analysis (ESMO Asia 2025) - P3 | "Consistent with the overall population, ami+laz meaningfully reduced the risk of death vs osi among Asian pts with 1L EGFRm advanced NSCLC and is projected to provide an OS benefit of >12 mo. These results among Asian pts confirm the findings from the overall MARIPOSA population, establishing ami+laz as a new SoC."

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

Prophylactic management of dermatologic adverse events with amivantamab + lazertinib treatment in 1L EGFR-mutated NSCLC: COCOON asian subset analysis (ESMO Asia 2025) - P2 | "Among Asian pts, COCOON DM reduced DAEI incidence & severity by Wk 12. The uncomplicated prophylactic COCOON DM regimen enhances the risk-benefit profile of 1L ami + laz for Asian pts with EGFR-mutated NSCLC."

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

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. (PubMed, N Engl J Med) - P3 | "The use of amivantamab-chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertions. (Funded by Janssen Research and Development; PAPILLON ClinicalTrials.gov number, NCT04538664.)."

EGFR exon 20 • Journal • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Preventing moderate to severe dermatologic adverse events in first-line EGFR-mutant advanced NSCLC treated with amivantamab plus lazertinib: Early success of the COCOON trial (ELCC 2025) - P2 | "With the simple, widely available, and easy to use COCOON DM regimen, ~2 out of every 3 pts did not experience any moderate to severe dermatologic AEs, and incidence of these skin AEs was reduced by 50% vs SoC DM. This regimen supported pts treatment with 1L ami + laz by reducing ami discontinuations due to AEs by ~50%."

Adverse events • Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Mechanisms of Acquired Resistance to First-Line Amivantamab Plus Lazertinib Vs Osimertinib: Updated Analysis from MARIPOSA (IASLC-WCLC 2025) - "In this updated analysis, significantly lower rates of EGFR and MET resistance alterations were seen in the amivantamab-lazertinib arm vs osimertinib. These findings further suggest that amivantamab-lazertinib, with its statistically significant and clinically meaningful survival benefit over osimertinib, is changing the underlying biology of EGFR -mutant disease."

Clinical • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • MET

Overall Survival with Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC. (PubMed, N Engl J Med) - P3 | "Amivantamab-lazertinib led to significantly longer overall survival among participants with previously untreated EGFR-mutated advanced NSCLC than osimertinib but was associated with an increased risk of adverse events of grade 3 or higher. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.)."

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

Validation Analysis of MET IHC as a Biomarker for Amivantamab-Lazertinib Response in Post-Osimertinib EGFR-Mutated NSCLC (IASLC-WCLC 2025) - P1 | "Nevertheless, amivantamab alone or with other agents is efficacious for advanced/metastatic NSCLC. Additional results will be reported at the meeting."

Biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR • MET

Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutant advanced NSCLC after disease progression on osimertinib: Outcomes by osimertinib resistance mechanisms in MARIPOSA-2. (ASCO 2025) - P3 | "Ami-chemo improved mPFS vs chemo across baseline resistance subgroups, including EGFR/MET dependent, independent, and unknown resistance. Ami-chemo is an important treatment option, regardless of baseline osi resistance mechanism, for pts with EGFR-mutant advanced NSCLC after progression on an EGFR TKI."

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

“The NCPE recommends that amivantamab, in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with advanced NSCLC with activating epidermal EGFR exon20ins mutations, should not be considered for reimbursement unless cost effectiveness can be improved relative to existing treatments” [For non-small cell lung cancer] (National Centre for Pharmacoeconomics, Ireland)

Reimbursement • Lung Cancer • Non Small Cell Lung Cancer • Oncology

“A full HTA is recommended to assess the clinical effectiveness and cost effectiveness of amivantamab for this indication compared with the current standard of care” [For non-small cell lung cancer] (National Centre for Pharmacoeconomics, Ireland)

HEOR • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B). (PubMed, J Clin Oncol) - P1/2 | "Sunvozertinib is efficacious at both 200 and 300 mg once daily in treating platinum-pretreated patients with advanced EGFR exon20ins NSCLC. The treatment-related adverse events of sunvozertinib were consistent with an EGFR tyrosine kinase inhibitor, with a more favorable safety profile at 200 mg than 300 mg once daily."

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

Decoding First-line strategies in EGFR-mutated NSCLC: A Computational Analysis of FLAURA2 vs. MARIPOSA (IASLC-TTLC 2025) - "Using the IPDfromKM method we found superior efficacy of osimertinibchemotherapy in comparison to amivantamab-lazertinib for patients with advanced EGFRm NSCLC, including high risk cohorts. As we await randomized studies to compare these strategies, here we demonstrate the potential of such computational analysis to aid in clinical decision making, especially in settings where multiple treatment options are currently approved. Figures: Not to be submitted with abstract, will include in poster."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • TP53

Intracranial and systemic progression on amivantamab in platinum-treated epidermal growth factor receptor exon 20 insertion-mutated advanced non-small cell lung cancer. (PubMed, Lung Cancer) - P1 | "Amivantamab monotherapy in post-platinum Ex20ins NSCLC demonstrated meaningful antitumor activity in participants, and intracranial-only progression was infrequent. Treatment of brain progression with SRS while continuing amivantamab appears feasible and tolerable."

Journal • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Amivantamab in Participants with Advanced Non-small Cell Lung Cancer (NSCLC) and MET Exon 14 Skipping Mutations: Final Results From the CHRYSALIS Study. (PubMed, J Thorac Oncol) - "The safety profile was consistent with previous reports of amivantamab in EGFR-mutant NSCLC. Amivantamab demonstrated clinically meaningful and durable antitumor activity in participants with METex14 advanced NSCLC, including those who progressed on prior MET therapies."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutated, advanced non-small cell lung cancer after disease progression on osimertinib: Second interim overall survival from MARIPOSA-2 (ESMO 2024) - P3 | "Background: In the phase 3 MARIPOSA-2 study (NCT04988295), amivantamab (ami)-chemotherapy (chemo; carboplatin/pemetrexed) showed superior progression-free survival (PFS) vs chemo in patients (pts) with EGFR-mutant, advanced non-small cell lung cancer (NSCLC) after progression on osimertinib (osi; HR, 0.48; 95% CI, 0.36–0.64; P<0.001). Ami-chemo numerically improved OS and significantly prolonged post-progression outcomes vs chemo in EGFR-mutant, advanced NSCLC post-osi."

Clinical • Late-breaking abstract • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • EGFR

Amivantamab plus lazertinib vs osimertinib in first-line (1L) EGFR-mutant (EGFRm) advanced NSCLC: Final overall survival (OS) from the phase III MARIPOSA study (ELCC 2025) - P3 | "Ami+laz is the first and only treatment to significantly reduce the risk of death vs osi in pts with 1L EGFRm advanced NSCLC. While the median has not yet been reached for ami+laz, it is expected to provide an OS benefit of at least 12 mo. These results further establish ami+laz as a new SoC in this population."

Clinical • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

First-line oral vinorelbine plus furmonertinib in refractory epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC): A multicenter, non-randomized, two-cohort study (ELCC 2026) - P4 | "Primary endpoint is investigator-assessed PFS. Secondary endpoints are objective response rate, disease control rate, OS, and safety."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • PD-L1

Clinical outcomes and molecular characterization of patients with uncommon EGFR-mutated NSCLC: A single-centre study (ELCC 2026) - "MPFS for osimertinib (osi) or lazertinib (lazer) monotherapy (n=27), osi + chemotherapy (n=4) and afatinib (n=3) were 10.0 mo (95% CI 6.2–30.3), 9.0 mo (95% CI 4.2–NR) and 16.7 mo (95% CI 12.9–NR), respectively. MPFS was not reached with amivantamab + lazer (n=3), chemotherapy ± immunotherapy (n=6) and zipalertinib (n=1). Progression occurred at 1.5 mo in one patient treated with sunvozertinib.Conclusions This real-world cohort provides broad clinical and molecular characterization of uncommon EGFR-mutated NSCLC and supports the need for dedicated prospective trials."

Clinical • Clinical data • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Estimated time toxicity associated with 1L use of 3rd gen EGFR TKI regiments in advanced non-small cell lung cancer in the European Union (ELCC 2026) - "The objective of this study was to estimate the time toxicity (TT) for patients associated with approved 1L treatments for EGFRm NSCLC over the first year of treatment in the European Union (EU).Methods This model estimates TT over the first year of treatment for osimertinib (osi), osimertinib + platinum pemetrexed chemotherapy (osi + plat pem), amivantamab + lazertinib (ami + laz) intravenous (IV), and ami + laz subcutaneous (SQ)...The largest difference between osi based regimens and ami + laz based regimens was prophylactic time with osi at 0 hours, osi + plat pem at 7 hours, and both ami + laz regimens at 219 hours. We estimate that SQ ami + laz will reduce drug administration time from 67 hours to 20 hours per year but will not impact prophylactic time.Conclusions It is important to consider time toxicity and overall treatment burden when discussing a patient's treatment goals, because our model estimates that there may be substantial differences in time..."

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