^
    3d
    A Phase 1/2 Study of D3S-002 as Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations (clinicaltrials.gov)
    P1/2, N=67, Recruiting, D3 Bio (Wuxi) Co., Ltd | Active, not recruiting --> Recruiting | Trial completion date: Apr 2028 --> Aug 2028 | Trial primary completion date: Apr 2028 --> Aug 2028
    Enrollment open • Trial completion date • Trial primary completion date • First-in-human
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    |
    BRAF V600E • EGFR mutation • KRAS G12C • BRAF V600 • EGFR L858R • EGFR T790M • KRAS G12D • ALK rearrangement • MET exon 14 mutation • EGFR L861Q • ROS1 fusion • EGFR G719X • MET mutation • EGFR S768I • RET rearrangement • KRAS G12 • KRAS G12S • KRAS Q61
    |
    D3S-002 • elisrasib (D3S-001)
    3d
    Stage 4A Lung Adenocarcinoma with Rare EGFR Exon 21 L861Q and Exon 18 G719A Co-Mutations Showing Complete PET-CT Response to Osimertinib: A Case Report. (PubMed, Case Rep Oncol)
    This case demonstrates that osimertinib can achieve an early, deep, and sustainable response in patients with a rare G719A/L861Q co-mutation. Prospective evidence is necessary for rare EGFR subtypes.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1)
    |
    EGFR mutation • EGFR L861Q
    |
    Tagrisso (osimertinib)
    8d
    ALINEAR: Trop2 NMR Concordance Study (clinicaltrials.gov)
    P=N/A, N=3400, Not yet recruiting, AstraZeneca
    New trial
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • ALK rearrangement • EGFR L861Q • ROS1 rearrangement • EGFR G719X • EGFR S768I
    |
    VENTANA® TROP2 (EPR20043) RxDx Assay
    22d
    A Durable Response to Low-Dose Afatinib After Progression on Osimertinib in Advanced Epidermal Growth Factor Receptor (EGFR) L861Q-Mutated Lung Adenocarcinoma: A Case Report. (PubMed, Cureus)
    As second-line therapy, he was treated with pembrolizumab plus carboplatin and pemetrexed for four cycles, followed by 13 cycles of maintenance pembrolizumab and pemetrexed, and subsequently five cycles of pembrolizumab monotherapy, maintaining stable disease until further progression. He was then started on low-dose afatinib (20 mg once daily) as third-line therapy, achieving a partial response that has been maintained for 18 months without severe adverse events. This case suggests that low-dose afatinib may provide durable disease control with acceptable tolerability after progression on osimertinib in advanced EGFR L861Q-mutated NSCLC.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1)
    |
    EGFR mutation • EGFR L861Q
    |
    Keytruda (pembrolizumab) • Tagrisso (osimertinib) • Gilotrif (afatinib) • carboplatin • pemetrexed
    24d
    Phase II Clinical Study of JS207 (PD-1/VEGF Bispecific Antibody) Combination Therapies in Patients With Driver Gene-Positive, Advanced Non-Small Cell Lung Cancer After Failure of TKI Therapy (clinicaltrials.gov)
    P2, N=78, Recruiting, Shanghai Junshi Bioscience Co., Ltd. | N=42 --> 78 | Trial completion date: Apr 2027 --> Apr 2028 | Trial primary completion date: Sep 2025 --> Sep 2026
    Enrollment change • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR L858R • HER-2 mutation • EGFR T790M • RET fusion • EGFR expression • HER-2 exon 20 insertion • ALK fusion • EGFR L861Q • RET mutation • ROS1 fusion • EGFR S768I • KRAS G12 • NTRK fusion
    |
    cisplatin • carboplatin • pemetrexed
    25d
    PD-L1 expression is associated with inferior outcomes independent of EGFR subtype in advanced non-small cell lung cancer with uncommon EGFR mutations treated with first-line second-generation EGFR-tyrosine kinase inhibitors. (PubMed, Cancer)
    In advanced NSCLC with uncommon EGFR mutations, first-line second-generation EGFR-TKI monotherapy shows no statistically significant efficacy differences across mutation subtypes. PD-L1 expression is inversely associated with outcomes, with prognostic value differing between primary tumors and metastatic lymph nodes, highlighting the importance of tissue sampling site in risk stratification.
    Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • EGFR mutation • PD-L1 overexpression • EGFR expression • EGFR L861Q • EGFR G719X • EGFR S768I • PD-L1 expression + EGFR mutation
    1m
    NEOVADE: Neoadjuvant Almonertinib Followed by Chemo-immunotherapy in II-IIIB EGFR-mutant NSCLC (clinicaltrials.gov)
    P2, N=32, Active, not recruiting, Guangdong Provincial People's Hospital | Trial completion date: Sep 2027 --> Apr 2026 | Recruiting --> Active, not recruiting
    Enrollment closed • Trial completion date • IO biomarker
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    carboplatin • albumin-bound paclitaxel • Ameile (aumolertinib) • AiRuiLi (adebrelimab)
    1m
    Study to Evaluate Sutetinib Maleate Capsule in Locally Advanced or Metastatic Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=99, Recruiting, Teligene US | Trial completion date: Jun 2026 --> Dec 2028 | Trial primary completion date: Jun 2026 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    sutetinib (SZMD4)
    2ms
    REZILIENT4: A Study to Assess the Efficacy and Safety of Zipalertinib Versus Placebo for Adjuvant Treatment in Participants With Stage IB-IIIA NSCLC With Uncommon EGFR Mutations, Following Complete Tumor Resection (clinicaltrials.gov)
    P3, N=360, Active, not recruiting, Taiho Oncology, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    EGFR L861Q • EGFR G719X • EGFR S768I
    |
    cisplatin • carboplatin • pemetrexed • zipalertinib (CLN-081)
    2ms
    ML41701: A Phase II Study of Atezolizumab in Combination With Bevacizumab, Carboplatin or Cisplatin, and Pemetrexed for EGFR-mutant Metastatic Non-small Cell Lung Cancer Patients After Failure of EGFR Tyrosine Kinase Inhibitors. (clinicaltrials.gov)
    P2, N=22, Completed, National Taiwan University Hospital | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Feb 2026 | Trial primary completion date: Dec 2024 --> Feb 2026
    Trial completion • Trial completion date • Trial primary completion date • IO biomarker
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Avastin (bevacizumab) • cisplatin • Tecentriq (atezolizumab) • carboplatin • pemetrexed
    2ms
    Epidermal Growth Factor Receptor (EGFR) atypical mutations in Non-Small-Cell Lung Cancer (NSCLC): 'where the streets have no name'. (PubMed, Crit Rev Oncol Hematol)
    To date, afatinib remains the only approved agent specifically indicated for tumors harboring selected atypical variants-namely S768I, L861Q, and G719X-based on regulatory approvals by the FDA and EMA in 2018...Specifically, we will examine the efficacy of first-, second-, and third-generation EGFR TKIs in this subgroup, discuss the mechanisms underlying resistance, and highlight the clinical implications of the recently proposed structure-function-based classification of EGFR mutations. Finally, we will review emerging evidence from ongoing clinical trials of novel therapeutic agents, including bispecific antibodies and next-generation inhibitors, which may offer new opportunities for patients with atypical EGFR-mutant NSCLC.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib) • Gilotrif (afatinib)
    2ms
    Combining Furmonertinib With Local Therapy for Inoperable Early-stage Lung Cancer: A Phase II Trial (clinicaltrials.gov)
    P2, N=45, Not yet recruiting, Shanghai Pulmonary Hospital, Shanghai, China
    New P2 trial
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Ivesa (firmonertinib)