Exkivity (mobocertinib) / Takeda - LARVOL DELTA

First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial. (PubMed, J Clin Oncol) - P3 | "The EXCLAIM-2 trial did not meet its primary end point. The efficacy of mobocertinib was not superior to platinum-based chemotherapy for first-line treatment of patients with EGFR ex20ins+ advanced/metastatic NSCLC."

Journal • P3 data • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Characterizing dermatologic toxicities of novel agents for patients with EGFR exon 20 insertion mutations in NSCLC (AAD 2026) - "Introduction: Epidermal growth factor receptor (EGFR) mutations are key oncogenic drivers in non-small-cell-lung cancer (NSCLC).1 Patients with exon 20 insertion mutations have historically been resistant to standard EGFR tyrosine kinase inhibitors (TKIs), however, emerging therapies for these patients include amivantamab, mobocertinib, and investigational TKIs.2 These therapies have unique dermatologic adverse events (dAEs) in severity and distribution compared to standard EGFR TKIs and have not been thoroughly documented.3 We queried our health system’s EHR for patients receiving these three therapy classes for EGFR exon 20 insertion mutations in NSCLC from December 1, 2015 to July 31, 2025... Among 27 patients, 18 (66.7%) experienced a dAE. The median time to dAE was 11 days (range of 2-62 days). The most common toxicity was acneiform rash, with 14/27 patients (51.9%)."

Clinical • EGFR exon 20 • Lung Cancer • Mucositis • Non Small Cell Lung Cancer • Pruritus • Solid Tumor • EGFR

OB-001 boost the brain penetration of multiple TKIs (AACR 2026) - "OB-001 selectively boosts brain exposure without substantially increasing systemic exposure. These data demonstrate that theoretically a pharmacokinetic window can be achevied with OB-001 whereby enhanced brain metatsases efficacy could be acheived for numerous kinase inhibitors without effecting systemic toxicity. These findings support OB-001 as a first-in-class CNS-targeted efflux modulating adjunct capable of elevating brain drug exposure beyond what is achievable by existing kinase inhibitors alone."

Oncology • Solid Tumor • ABCB1 • ABCG2

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

Sunvozertinib A Next-Generation EGFR Exon 20 Insertion Inhibitor Transforming NSCLC Therapy. (PubMed, Zhongguo Ying Yong Sheng Li Xue Za Zhi) - "Recently developed agents such as amivantamab and mobocertinib have improved response rates, yet challenges related to tolerability, CNS penetration, and durability of benefit persist. Early-phase clinical trials, including the WU-KONG series, have reported promising clinical efficacy, including objective response rates ranging from 44-60% in previously treated patients and meaningful activity in treatment-naïve cohorts. The tolerability profile of the drug seems manageable, with diarrhea, rash, and stomatitis among the most commonly observed adverse events; these, however, tend to be milder compared with other agents targeting EGFR Ex20ins."

Journal • Review • Dental Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR

Evolving treatment strategies for EGFRex20ins-mutated NSCLC: a comprehensive review of Amivantamab's role and future directions. (PubMed, Ecancermedicalscience) - "Lastly, we contextualise Amivantamab in the current treatment landscape by contrasting it with mobocertinib and highlighting current studies that aim to improve central nervous system activity and overcome resistance mechanisms. This review highlights the therapeutic benefit of Amivantamab in EGFRex20ins-mutated NSCLC and offers guidance for future research in this quickly developing area."

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

FDA Approval Summary: Mobocertinib for Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations. (PubMed, Clin Cancer Res) - P1/2 | "Product labeling includes a Boxed Warning for QTc prolongation and Torsades de Pointes. This is the first approval of an oral targeted therapy for patients with advanced EGFR exon 20 insertion mutation-positive NSCLC."

EGFR exon 20 • FDA event • Journal • Dental Disorders • Fatigue • Lung Cancer • Musculoskeletal Diseases • Musculoskeletal Pain • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • Stomatitis • EGFR

Emerging phase 1 data of BLU-451 in advanced NSCLC with EGFR exon 20 insertions. (ASCO 2023) - P1/2 | "Background: In patients (pts) with NSCLC harboring EGFR exon 20 insertions (ex20ins), treatment options are limited, with platinum-based chemotherapy with/without programmed death-ligand 1 inhibitors being the standard of care in first line, and recent accelerated approvals of mobocertinib and amivantamab in the USA for second-line treatment. As of the data cutoff, BLU-451 monotherapy was generally well tolerated, with early evidence of clinical activity in heavily pretreated pts with EGFR ex20ins–positive NSCLC. Early data at initial dose levels consisted of tumor reduction including responses, CNS activity, and ctDNA responses. The dose escalation is ongoing to determine the MTD and/or RP2D."

EGFR exon 20 • Metastases • P1 data • CNS Disorders • Cough • Fatigue • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pruritus • Respiratory Diseases • Solid Tumor • EGFR • PD-L1

EXCLAIM-2: Phase III trial of first-line (1L) mobocertinib versus platinum-based chemotherapy in patients (pts) with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins)+ locally advanced/metastatic NSCLC (ESMO Asia 2023) - P3 | "Methods This open-label, multicenter study (NCT04129502) randomized pts with untreated EGFR ex20ins+ locally advanced/metastatic NSCLC to (1:1) mobocertinib 160 mg PO daily or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2/carboplatin AUC 5 IV every 3 weeks for 4 cycles followed by maintenance pemetrexed. Conclusions At IA, mobocertinib efficacy was similar but not superior to 1L platinum-based chemotherapy. Safety profiles were similar to previous reports, with no new safety concerns identified."

Clinical • EGFR exon 20 • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Amivantamab and Mobocertinib in Exon 20 insertions EGFR Mutant Lung Cancer, Challenge To The Current Guidelines. (PubMed, Transl Oncol) - "Our analysis has implications beyond patients with exon 20 insertion. In an era with growing identification of new and rarer molecular entities, misguided incorporation of new compounds into practice may obstruct trial enrollment in decisive clinical trials."

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

Efficacy and safety of later-line targeted therapies in advanced non-small cell lung cancer with EGFR exon 20 insertion mutations: a systematic review. (PubMed, Front Pharmacol) - "Recent developments in targeted therapies, including agents such as amivantamab, mobocertinib, and sunvozertinib, have shown promise in patients with pretreated ex20ins-positive NSCLC. No amendments were made to the registered protocol after commencement of the review. The full review protocol can be accessed on the PROSPERO database (Registration number: CRD420251056825)."

IO biomarker • Journal • Review • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Comparing the effect of traditional and novel tyrosine kinase inhibitors for epidermal growth factor receptor exon 20 insertions by molecular dynamics simulation. (PubMed, J Int Med Res) - "When binding to osimertinib, ASV- and SVD-EGFR still revealed two energy minima on their free energy landscapes, but with considerably less conformational probability distribution at collective variable 2 >1.00 Å. In contrast, mobocertinib eliminated the energy minima at collective variable 2 >1.00 Å while decreasing the K745-E762 salt bridge formation rates.ConclusionsMobocertinib outperforms osimertinib in targeting specific subtypes of EGFR exon 20 insertions, highlighting its ability to restore the inactive state of this protein."

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

Efficacy of zipalertinib in Asian patients with EGFR exon 20 insertion mutated (Ex20ins) advanced non-small cell lung cancer (NSCLC) (ESMO Asia 2025) - P3 | "Here we report on the efficacy and safety of zipalertinib in pts from Asia vs the rest of world (ROW). Pts who have progressed on chemotherapy with or without prior amivantamab (including those with amivantamab and other ex20ins target therapy, such as mobocertinib) were treated with zipalertinib at 100 mg oral twice daily. Zipalertinib demonstrated similarly meaningful clinical benefit in pts from Asia and ROW. Zipalertinib was likewise tolerable and demonstrated a manageable safety profile in both groups."

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

Reversed phase HPLC analysis of mobocertinib and its impurities and studies on the structure and biological activity of a new degradation product. (PubMed, Front Chem) - "Imp-A, a novel compound, demonstrated promising anticancer activity in vitro. However, further in vivo studies are required to fully assess its therapeutic potential, which may hold promise for clinical applications in cancer treatment."

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

Poziotinib for EGFR exon 20-insertion NSCLC: Clinical efficacy of the phase 2 ZENITH trial and differential impact of EGFR exon 20 insertion location on sensitivity. (PubMed, Nat Commun) - P1/2, P2 | "In vitro studies show that afatinib, poziotinib, and zipalertinib more potently inhibited near-loop than far-loop insertions, whereas mobocertinib has similar IC50 in both groups. In comparison, in the previously published EXCLAIM trial (NCT02716116), mobocertinib demonstrates similar activities across both groups in tumor size reduction (-38.5% vs. -34.1%, p = 0.59) and PFS (12.0 vs. 13.0 months, p = 0.99). Therefore, EGFRex20ins location differentially impacts the sensitivity of TKIs."

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

Resistance Mechanisms of Novel Targeted Therapies to EGFR Exon 20 Insertion Mutation-Positive Non-Small Cell Lung Cancer (IASLC-WCLC 2025) - "Two patients with p.A763_Y764insFQEA who received afatinib therapy developed EGFR T790M as the resistance mechanism. Among 10 patients who received mobocertinib (n = 7), sunvozertinib (n = 2) or furmonertinib (n = 1), baseline EGFR mutations preserved in post-treatment tissue samples in 9 (90%) patients, EGFR amplification was detected in 5 (50%) patients...Conclusions : EGFR amplification is the most common resistance mechanism of novel EGFR inhibitors targeted on EGFR exon 20 insertion mutation. The resistance mechanisms of amivantamab therapy warrant further study."

EGFR exon 20 • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDK4 • EGFR • MDM2 • MET • MYC

Advances in the management of lung & gastro-intestinal cancers: clinical studies review from ASCO 2022/2023 annual meetings. (PubMed, Cancer Treat Res Commun) - "Additionally, novel therapeutic options such as Mobocertinib and sotorasib were identified as offering new hope for patients with specific lung cancers. Furthermore, the PROTECT study underscored the crucial importance of efforts to reduce severe chemotherapy-related side effects, potentially enhancing patients' quality of life. These findings highlight the significance of ASCO meetings as a vital source of information and collaboration in the fight against cancer, providing valuable insights for the clinical management of this complex disease."

Journal • Review • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Exceptional Response to Immunotherapy-based Treatment in Compound EGFR-Mutated Oligometastatic Pulmonary Sarcomatoid Carcinoma: A Case Report. (PubMed, J Immunother Precis Oncol) - "The patient exhibited disease progression despite sequential treatment with EGFR TKIs, including osimertinib, afatinib, and mobocertinib, in combination with chemotherapy. The treatment strategy was then shifted to immunotherapy with pembrolizumab alongside carboplatin and paclitaxel, leading to a remarkable response...This case challenges the conventional paradigm that EGFR-mutated NSCLC does not benefit from immunotherapy, highlighting the potential for an alternative treatment approach in rare subtypes such as PSC. Our findings emphasize the importance of comprehensive molecular profiling and a personalized treatment strategy to optimize outcomes in aggressive and refractory lung cancers."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • EGFR

Sunvozertinib (Zegfrovy) for NSCLC. (PubMed, Med Lett Drugs Ther) - No abstract available

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

In silico drug repurposing targeting fusion and nucleoprotein of human metapneumovirus: A step toward pandemic preparedness. (PubMed, Indian J Pharmacol) - "The study highlights mobocertinib, rutin, and levetiracetam as promising repurposed drugs against HMPV. While mobocertinib exhibited the strongest predicted binding affinity, levetiracetam demonstrated the best pharmacokinetic profile, making it a particularly viable candidate for further experimental validation. These results validate the usefulness of in silico drug repurposing in addressing unmet antiviral needs and warrant preclinical studies to evaluate therapeutic efficacy."

Journal

Electrophysiological consequences of acute mobocertinib exposure in isolated rat and guinea-pig hearts and transfected cell lines. (PubMed, Biochem Biophys Res Commun) - "These data suggest that mobocertinib exerts acute, direct cardiac electrophysiological effects-predominantly via hERG and Cav1.2 inhibition-providing a mechanistic basis for observed QT prolongation and conduction delay in patients."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • NAV1

Effects of antihypertensive drugs on the metabolism of mobocertinib in rats both in vitro and in vivo. (PubMed, Drug Metab Dispos) - "The inhibitory mechanism of mobocertinib was further investigated for nicardipine, irbesartan, telmisartan, carvedilol, prazosin hydrochloride, and spironolactone. In this study, the most common antihypertensive drugs were found to inhibit the metabolism of mobocertinib in vitro. We found that benidipine, nicardipine, telmisartan, and irbesartan inhibited the metabolism of mobocertinib in vitro and in vivo."

Journal • Preclinical

Real-world use of accelerated approval oncology drugs subsequently withdrawn in the United States. (ASCO 2025) - " Included AA drugs were mobocertinib (NSCLC), sacituzumab govitecan (bladder cancer), atezolizumab (breast cancer), nivolumab (SCLC), and pembrolizumab (SCLC). Findings indicate mixed real-world uptake of AA therapies and no consistent differences in patient characteristics. It appears care teams promptly follow regulatory guidance and cease initiating withdrawn AA drugs after IW. Pembrolizumab and nivolumab in SCLC indications that are retained in the clinical practice guidelines seem to be the exception to this trend."

Clinical • Real-world • Real-world evidence • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Orally effective FDA-approved protein kinase targeted covalent inhibitors (TCIs): A 2025 update. (PubMed, Pharmacol Res) - "The clinical efficacy of ibrutinib, a Bruton tyrosine kinase blocker, in the treatment of mantle cell lymphoma following its 2013 approval helped to overcome a general bias against the development of irreversible drug inhibitors. Other approved targeted covalent inhibitors include acalabrutinib and zanubrutinib, which also block Bruton tyrosine kinase. Afatinib, dacomitinib, lazertinib, mobocertinib, and osimertinib inhibit members of the epidermal growth factor receptor family (ErbB1/2/3/4) and are used in the treatment of non-small cell lung cancers. Neratinib inhibits ErbB2 and is used in the management of ErbB2/HER2-positive breast cancer. Futibatinib blocks the fibroblast growth factor receptor family and is prescribed for the treatment of cholangiocarcinoma while ritlecitinib, which inhibits JAK3, is used in the management of alopecia areata. The eleven drugs considered in this review have a common mechanism of action involving the addition of a protein cysteine..."

FDA event • Journal • Review • Alopecia • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Lung Cancer • Lymphoma • Mantle Cell Lymphoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BTK • EGFR • FGFR

Real-world treatment patterns of patients with EGFR exon 20 insertion-mutated advanced NSCLC treated with amivantamab or mobocertinib after platinum-based chemotherapy: A multi-database cohort study. (PubMed, Cancer Treat Res Commun) - "This retrospective study described patient characteristics, treatment patterns, and outcomes in patients with EGFR exon20ins-mutated advanced or metastatic NSCLC who received amivantamab or mobocertinib monotherapy after platinum-based chemotherapy. Real-world patients treated with amivantamab experienced TTNTD and TTD consistent with the median progression-free survival observed in its registrational trial, while patients treated with mobocertinib exhibited faster disease progression and a higher frequency of treatment discontinuation."

HEOR • Journal • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR