The management of human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) remains a significant clinical challenge, with limited effective and accessible treatment options beyond antibody-drug conjugates such as trastuzumab deruxtecan (T-DXd)...Following chemotherapy and sintilimab failure in August 2025 due to progressive disease, furmonertinib rechallenge at 160 mg/day again induced a response within 5 days, with no grade ≥3 adverse events...The structural homology between HER2 p.Y772_A775dup and EGFR exon 20 "near-loop" insertions may facilitate TKI binding. Furmonertinib emerges as a potential, cost-effective oral therapeutic alternative for this patient population, especially when standard therapies are not feasible, warranting further prospective investigation.

13 days ago

Journal

HER-2 (Human epidermal growth factor receptor 2)

EGFR mutation • HER-2 mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation • HER-2 exon 20 mutation

Tyvyt (sintilimab) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Ivesa (firmonertinib)

16d

FURTHER: Study of Furmonertinib in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Activating, Including Uncommon, Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Mutations (clinicaltrials.gov)

P1, N=160, Active, not recruiting, ArriVent BioPharma, Inc. | Trial completion date: Dec 2025 --> Dec 2026

16 days ago

Trial completion date

HER-2 (Human epidermal growth factor receptor 2)

HER-2 exon 20 insertion • EGFR G719X • EGFR S768I

Ivesa (firmonertinib)

A Study of NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1) (clinicaltrials.gov)

P1, N=200, Recruiting, Nuvalent Inc. | N=150 --> 200 | Trial completion date: Mar 2026 --> Feb 2027 | Trial primary completion date: Mar 2026 --> Jan 2027

1 month ago

Enrollment change • Trial completion date • Trial primary completion date • First-in-human

HER-2 (Human epidermal growth factor receptor 2)

HER-2 amplification • HER-2 exon 20 insertion • HER-2 exon 20 mutation

NVL-330

NCI-2017-00831: Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC (clinicaltrials.gov)

P2, N=93, Terminated, M.D. Anderson Cancer Center | Trial completion date: Dec 2027 --> Feb 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2027 --> Feb 2026; <75% participation

1 month ago

Trial completion date • Trial termination • Trial primary completion date

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)

EGFR mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation

FoundationOne® CDx • Guardant360® CDx • cobas® EGFR Mutation Test v2 • therascreen® EGFR RGQ PCR Kit

Pozenveo (poziotinib)

PHOENIX: QL1706 Plus Chemotherapy and Bevacizumab in AGA-Resistant, PD-L1 ≥50% Non-Squamous NSCLC (clinicaltrials.gov)

P2, N=61, Not yet recruiting, Guangdong Association of Clinical Trials

1 month ago

New P2 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) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • RET fusion • HER-2 exon 20 insertion • ROS1 fusion • KRAS G12 • HER-2 exon 20 mutation

PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay

Avastin (bevacizumab) • cisplatin • carboplatin • pemetrexed • Qibeian (iparomlimab/tuvonralimab)

2ms

Glumetinib combined with platinum-based chemotherapy for the treatment of MET-overexpressing locally advanced or metastatic non-small cell lung cancer: A single-arm, multicenter study (ChiCTR2600117342)

P1, N=48, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

2 months ago

New P1 trial

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)

EGFR mutation • BRAF mutation • BRAF V600 • HER-2 mutation • RET fusion • MET overexpression • HER-2 exon 20 insertion • ALK fusion • RET mutation • ROS1 fusion • MET mutation • NTRK fusion

carboplatin • pemetrexed • Haiyitan (gumarontinib)

2ms

NCI-2017-00831: Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC (clinicaltrials.gov)

P2, N=93, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

2 months ago

Trial completion date • Trial primary completion date

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)

EGFR mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation

FoundationOne® CDx • Guardant360® CDx • cobas® EGFR Mutation Test v2 • therascreen® EGFR RGQ PCR Kit

Pozenveo (poziotinib)

2ms

Case Report: Perioperative application of trastuzumab deruxtecan in HER2 exon 20 mutation-positive non-small cell lung cancer. (PubMed, Front Pharmacol)

This case shows that perioperative treatment with T-DXd could induce tumor regression and sustain remission, while MRD monitoring enables early detection of molecular progression. These findings emphasize the potential of combining T-DXd and MRD monitoring to tailor treatment to improve outcomes in HER2-mutant NSCLC.

2 months ago

Journal • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53)

TP53 mutation • HER-2 mutation • HER-2 exon 20 insertion • HER-2 exon 20 mutation

Enhertu (fam-trastuzumab deruxtecan-nxki)

3ms

First-In-Human Study of STX-721/PFL-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR or HER2 Exon 20 Insertion Mutations (clinicaltrials.gov)

P1/2, N=251, Recruiting, Pierre Fabre Medicament | N=185 --> 251 | Trial completion date: Jun 2028 --> Dec 2029 | Trial primary completion date: Jun 2027 --> Dec 2029

3 months ago

Enrollment change • Trial completion date • Trial primary completion date • First-in-human

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)

EGFR mutation • HER-2 mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation

STX-721

5ms

Successful Rechallenge of Trastuzumab Deruxtecan Following Early Detection of ILD in a Patient with Non-small Cell Lung Carcinoma Harboring HER2 Exon 20 Insertion. (PubMed, Intern Med)

She received eight additional cycles (nine in total), resulting in tumor regression without ILD recurrence. Given that T-DXd is currently the only approved HER2-targeted therapy for NSCLC in our country, this case underscores the importance of early detection and appropriate management of ILD to maximize the therapeutic benefits.

5 months ago

Journal

HER-2 (Human epidermal growth factor receptor 2)

HER-2 exon 20 insertion • HER-2 exon 20 mutation

Enhertu (fam-trastuzumab deruxtecan-nxki)

6ms

Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer. (PubMed, Cancer Discov)

We furthermore demonstrate the activity of sevabertinib in a cancer cell line dependent on a fusion of NRG1, a ligand for the HER2 family member and heterodimerization partner, HER3. Finally, we report patient responses to sevabertinib from a Phase 1/2 clinical trial, indicating potential benefit for patients with HER2-mutant lung cancer.

6 months ago

Journal

ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)

HER-2 amplification • HER-2 mutation • EGFR wild-type • HER-2 exon 20 insertion • NRG1 fusion • HER-2 exon 20 mutation

Hyrnuo (sevabertinib)

7ms

P1, N=160, Active, not recruiting, ArriVent BioPharma, Inc. | Trial completion date: Sep 2025 --> Dec 2025 | Trial primary completion date: Sep 2025 --> Jun 2025

7 months ago

Trial completion date • Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2)

HER-2 exon 20 insertion • EGFR G719X • EGFR S768I

Ivesa (firmonertinib)