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

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

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

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

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

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

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

Efficacy of zipalertinib in NSCLC patients with EGFR exon 20 insertion mutations who received prior platinum-based chemotherapy with or without amivantamab. (ASCO 2025) - P1/2 | "Of the 51 pts with prior ami, 30 had no other ex20ins-directed therapy, while 21 had also received other ex20ins drugs (such as mobocertinib, sunvozertinib, BLU-451, or poziotinib), the cORR was 30.0% and 14.3%, respectively. Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in pts with exon20ins NSCLC who have received prior platinum-based chemotherapy and for those who received prior amivantamab, a significant and growing unmet need. BICR assessed tumor responses per RECIST v1.1.CR=complete response, PR=partial response, SD=stable disease."

Clinical • EGFR exon 20 • IO biomarker • Anemia • Dental Disorders • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR

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

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

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

Overall survival for amivantamab plus lazertinib versus osimertinib as first-line treatment in Asian participants with EGFR-mutant advanced NSCLC: A MARIPOSA subset analysis (Lung Cancer) - "Of 1074 randomized participants, 629 self-identified as Asian (amivantamab-lazertinib:250; osimertinib:251; lazertinib:128). At a median follow up of 38.7 months, amivantamab-lazertinib significantly prolonged OS versus osimertinib among Asian participants. Median OS was not reached (NR; 95 % CI, NR-NR) for amivantamab-lazertinib versus 38.4 months (95 % CI, 35.1-NR) for osimertinib (HR, 0.74; 95 % CI, 0.56–0.97; nominal P = 0.026)....At 36 months, 61 % and 53 % were alive in the amivantamab-lazertinib and osimertinib arms."

P3 data • Non Small Cell Lung Cancer

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 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

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

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

AMIGO: A phase 2 trial of amivantamab in EGFR or MET-amplified gastroesophageal adenocarcinoma (GEA). (ASCO-GI 2026) - P2 | "Ami monotherapy was effective in heavily pre-treated pts with GEA, including tumors with both EGFR and MET amps, and the primary endpoint was met. Despite persistent target lesion control, responders developed mixed responses attributable to resistance via EGFR/MET heterogeneity, co-occurring alterations, and CNS metastasis development. EGFR/MET targeting warrants further evaluation in combination with chemotherapy to address heterogeneity, a common barrier to single agent targeted therapy in GEA."

P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • 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

Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy in Relapsed/Refractory EGFR-mutant NSCLC (IASLC-WCLC 2022) - P1 | " The LACP (lazertinib, amivantamab, carboplatin, pemetrexed) cohort of the CHRYSALIS-2 study (NCT04077463) enrolled patients with EGFR-mutant NSCLC whose disease progressed on or after treatment with an EGFR TKI as last line of therapy (maximum of 3 prior lines)... Enrolled patients have received a median of 2 (range, 1-3) prior lines of therapy, including osimertinib (n=14), gefitinib (n=3), and afatinib (n=3)... Amivantamab in combination with lazertinib and chemotherapy yielded high overall response rates in patients who progressed on EGFR TKIs as prior line of therapy. The safety profile of the LACP regimen was consistent with the individual agents, with no evidence of new safety signals or additive toxicity."

Combination therapy • Fatigue • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • EGFR

Subcutaneous amivantamab vs intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results, including overall survival (OS), from the global, phase 3, randomized controlled PALOMA-3 trial. (ASCO 2024) - P3 | "PALOMA-3 (NCT05388669) evaluated SC ami+laz vs IV ami+laz for pharmacokinetics (PK), efficacy, and safety among pts with EGFR Ex19del or L858R-mutated advanced NSCLC and disease progression on osimertinib and platinum-based chemotherapy. SC ami demonstrated noninferior PK and ORR compared to IV. Unexpectedly, DoR, PFS, and OS were longer in the SC arm vs IV, suggesting that the route of administration or formulation may affect outcomes. The safety profile was improved for SC ami, with lower IRR and VTE rates."

Clinical • Combination therapy • Late-breaking abstract • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Amivantamab, lazertinib and bevacizumab in EGFR-mutant advanced NSCLC with acquired resistance to 3rd generation EGFR-TKI: Final results from the phase II ETOP AMAZE-lung trial (ELCC 2025) - P2 | "Amivantamab (ami), an EGFR-MET bispecific antibody, is approved in combination with chemotherapy for EGFR-mutant NSCLC patients (pts) after progression on osimertinib (osi) based on the MARIPOSA-2 trial. Ami-laz-bev combination demonstrated durable antitumour activity and represents a promising chemo-sparing alternative after progression on osi. Safety was consistent with known toxicity profiles."

Clinical • Metastases • P2 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Dermatologic prophylaxis and impact on patient-reported outcomes in first-line EGFR-mutant advanced NSCLC treated with amivantamab plus lazertinib: Results from the phase 2 COCOON trial. (ASCO 2025) - P2 | "COCOON DM included oral doxycycline/minocycline (100 mg BID Wks 1–12), clindamycin 1% lotion on scalp (QD Wks 13–52), chlorhexidine 4% to wash hands and feet QD, and non-comedogenic ceramide-based moisturizer to body and face QD. Among pts with EGFR-mutant advanced NSCLC, COCOON DM reduced the severity of dermatologic AEs and reduced the impact of those AEs on QoL compared to SoC DM."

Clinical • Metastases • P2 data • Patient reported outcomes • Dermatopathology • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Amivantamab in patients with NSCLC with MET exon 14 skipping mutation: Updated results from the CHRYSALIS study. (ASCO 2022) - P1 | "Median age was 70 y (range, 43-88), 58% were women, median prior lines of therapy was 2 (range, 0-10) [eg, crizotinib (n=13), capmatinib (n=11), tepotinib (n=5), anti-MET antibody (n=1)], and 23% had history of brain metastases at baseline. Amivantamab demonstrates anti-tumor activity in primary METex14 NSCLC including after prior MET inhibitor treatment. Enrollment is ongoing and updated data will be shown."

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

Pivotal topline data from the phase 1/2 TRIDENT-1 trial of repotrectinib in patients with ROS1+ advanced non-small cell lung cancer (NSCLC) (AACR-NCI-EORTC 2022) - P1/2 | "He played a monumental role in developing repotrectinib, lazertinib, amivantamab, and other targeted- and immuno-therapies, many of which were acknowledged for breakthrough therapy designation and FDA approval. Repotrectinib achieves durable activity, including intracranial responses, in TKI-naïve and TKI-pretreated patients with ROS1+ advanced NSCLC, and those with ROS1 G2032R. Repotrectinib safety is well characterized, manageable, and compatible with long-term use."

Clinical • Late-breaking abstract • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1