On September 9, 2025 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported the presentation of new findings on its leading assets, ZEGFROVY (sunvozertinib) and golidocitinib, in non-small cell lung cancer (NSCLC) at the 2025 World Conference on Lung Cancer (WCLC), held September 6–9 in Barcelona, Spain (Press release, Dizal Pharma, SEP 9, 2025, View Source [SID1234655886]).

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ZEGFROVY: Targeting EGFR exon20ins and a wide spectrum of EGFR mutations

The latest data from the multinational pivotal WU-KONG1 Part B (WU-KONG1B) study for ZEGFROVY were presented in an oral session at the conference and simultaneously published in the Journal of Clinical Oncology. Based on results from WU-KONG1B, ZEGFROVY received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2025 as the only targeted oral therapy for NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins).

ZEGFROVY demonstrated a favorable benefit/risk profile in patients with platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. The study showed robust and durable antitumor activity with a manageable safety profile. (#MA08.01).

In addition to the oral presentation, multiple studies of ZEGFROVY were presented at the WCLC, highlighting its potential across a broad range of NSCLC patients, including those with EGFR exon20ins across all lines of therapy, uncommon EGFR and HER2 mutations, EGFR-sensitive mutation and co-mutations, and EGFR mutations resistant to EGFR TKIs. Both monotherapy and combination regimens were evaluated.

In EGFR exon20ins NSCLC, ZEGFROVY demonstrated promising antitumor efficacy and a tolerable safety profile across first- and second- line, as well as adjuvant and neoadjuvant treatment settings.

ZEGFROVY combined with anlotinib achieved an objective response rate (ORR) of over 80% and a disease control rate (DCR) of 100% in treatment-naïve EGFR exon20ins NSCLC (#P3.12.43).
In previously treated patients, ZEGFROVY combined with bevacizumab achieved a DCR of 100%, with target tumor lesion shrinkage observed in 85.7% of patients. With a median follow-up of 15.2 months, the median duration of response (DoR) was 19.1 months, and three patients (3/14) remained in response at the data cut-off (#P2.10.13).
Real-world cases supported the potential of ZEGFROVY in early- and advanced- stage NSCLC patients with EGFR exon20ins.

As a neoadjuvant therapy, ZEGFROVY showed encouraging clinical benefit, with all 3 patients achieving an obvious partial response (PR) before surgery. (#EP.07.49).
In the adjuvant setting, ZEGFROVY showed sustained efficacy and tolerable safety profiles, helping patients successfully pass the 1-year after surgery, a peak period for disease recurrence (#EP.07.55).
In the first-line maintenance setting, ZEGFROVY showed sustained efficacy and safety in lung adenocarcinoma patients who were intolerant to immunotherapy and chemotherapy (#EP.12.47).
In NSCLC patients harboring uncommon EGFR mutations, ZEGFROVY combined with anlotinib demonstrated promising efficacy, including one patient who achieved complete remission of intracranial lesions (#P3.12.43). In a separate real-world case series, ZEGFROVY exhibited clinical efficacy in advanced NSCLC with HER2 exon20ins, with tumor shrinkage obviously observed post-prior treatment failures (#EP.12.46).

In treatment-naïve NSCLC patients with EGFR-sensitive mutation and co-mutations, ZEGFROVY in combination with anlotinib achieved an ORR of 77.8% and a DCR of 100% (#P3.12.22). In NSCLC patients with EGFR mutations who failed prior EGFR-TKI therapies, ZEGFROVY, both as monotherapy (#EP.12.43) and in combination with chemotherapy (#P3.12.47), was well tolerated and demonstrated encouraging antitumor activity.

Golidocitinib: Janus kinase 1 (JAK1) only inhibitor Plus Anti-PD-1 in Anti-PD-1 Treated Advanced NSCLC

Resistance to first-line immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) leads to limited treatment options and poor prognosis. Preclinical and early clinical data have shown synergistic effects between JAK inhibitors and anti-PD-1, suggesting a promising therapeutic strategy in this population. Golidocitinib in combination with anti-PD-1 was being evaluated in immune-resistant NSCLC patients. The study showed a well-tolerated profile, with no DLTs observed in the dose-escalation phase. Ongoing enrollment and data collection will provide deeper insights into clinical utility of golidocitinib (#P1.11.74).

Dr. Xiaolin Zhang, CEO of Dizal, remarked, "Dizal is advancing therapies for patients with NSCLC across EGFR exon 20 insertion, uncommon and EGFR-sensitizing mutations to address significant unmet medical needs. Through scientific innovation, we aim to deliver safe, effective and transformative treatments to patients worldwide."

On September 9, 2025 ArriVent BioPharma, Inc. (Company or ArriVent) (Nasdaq: AVBP), a clinical-stage company dedicated to accelerating the global development of innovative biopharmaceutical therapeutics, reported positive final proof-of-concept data from the randomized global Phase 1b FURTHER trial for first-line firmonertinib monotherapy in patients with non-small cell lung cancer (NSCLC) harboring EGFR PACC mutations at the IASCLC 2025 annual World Conference on Lung Cancer (WCLC), in Barcelona, Spain (Press release, ArriVent Biopharma, SEP 9, 2025, View Source [SID1234655873]).

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"Our 16-month prolonged progression free survival with once daily oral firmonertinib monotherapy has been maintained with 16.5 months of median follow up and we are particularly encouraged by the CNS responses including CNS complete responses" said Bing Yao, Ph.D., Chairman and Chief Executive Officer of ArriVent. "Together this data reinforces the potential of firmonertinib to address key unmet needs in the global EGFR mutant NSCLC treatment landscape. Additionally, the rapid clearance of PACC ctDNA in frontline patients observed across a broad range of PACC mutations, including those with frequent, less frequent and compound PACC mutations, is consistent with the broad activity of firmonertinib in PACC mutant NSCLC. We expect to enroll the first patient in our global registrational ALPACCA Phase 3 trial in frontline PACC patients in the second half of the year."

Key Highlights of Longer-term Final Analysis Data for Firmonertinib Monotherapy:

● Maintained Clinically Meaningful PFS and Durable Responses
o 16.0 months mPFS with firmonertinib once daily 240 mg by BICR, with majority of patients remaining on study
o 14.6 months median duration of response with firmonertinib 240 mg by BICR
o 68.2% and 43.5% confirmed ORR by BICR at 240 mg and 160 mg, respectively
◾ Confirmed responses at first tumor assessment in the majority of patients
◾ Responses across a wide range of EGFR PACC mutations including most frequent (G719X, S768I), less frequent (E709X, V774M) and compound mutations

o 42.9% (6/14) CNS confirmed ORR and 35.7% (5/14) CNS confirmed CRs in CNS evaluable disease front-line patients by BICR

● Safety Profile Continues to be Consistent with No New Safety Signals
o Generally well-tolerated and manageable safety profile maintained over longer treatment duration
o Most frequent treatment-related adverse events include diarrhea, hepatic enzyme elevation, rash, stomatitis, and dry skin
o No new safety findings with further follow up and safety profile remains consistent with EGFR-TKI class

● Rapidly Decreased or Cleared PACC ctDNA in Frontline Patients
o 82% (9/11) and 79% (11/14) ctDNA clearance in frontline PACC patients treated with firmonertinib at 240 mg and 160 mg, respectively, in patients with detectable PACC ctDNA at baseline
o Consistent decreases in ctDNA across different PACC mutations were observed including in patients with frequent, less frequent and compound mutations

On September 9, 2025 Taiho Oncology, Inc., and Cullinan Therapeutics, Inc., reported new data from the REZILIENT1 and REZILIENT2 trials of zipalertinib, an oral EGFR tyrosine kinase inhibitor, in patients with advanced or metastatic non-small cell lung cancer (NSCLC) (Press release, Taiho, SEP 9, 2025, View Source [SID1234655887]). These data will be presented at the IASLC 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer as mini oral presentations on September 9 during the "MA08 – Common and Uncommon EGFR Mutations, New Treatments in the Horizon" session, from 11:30 a.m. – 12:45 p.m. CEST.

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A mini oral presentation will highlight updated data from the pivotal Phase 2b REZILIENT1 trial of zipalertinib, focused on patients with NSCLC harboring EGFR ex20ins mutations, who have been previously treated with amivantamab.1

A second mini oral presentation will highlight Phase 2b preliminary efficacy and safety results from the ongoing, uncommon non-ex20ins EGFR mutations cohort of the REZILIENT2 trial of zipalertinib in patients with advanced or metastatic NSCLC harboring ex20ins and uncommon non-ex20ins EGFR mutations.2

"We’re pleased to share longer-term follow-up data from the REZILIENT1 study of zipalertinib for patients with NSCLC harboring EGFR ex20ins mutations who have been previously treated with amivantamab," said Zofia Piotrowska, MD, Associate Professor of Medicine, Harvard Medical School and lung cancer clinical oncologist at the Mass General Cancer Center. "Despite recent treatment advancements, a significant medical need exists for this patient population, underscoring the importance of these data."

"Uncommon non-exon 20 insertion EGFR mutations represent a significant clinical challenge, as they exhibit variable and often suboptimal responses to currently approved tyrosine kinase inhibitors," said Hibiki Udagawa, MD, PhD, thoracic medical oncologist, National Cancer Hospital East, Japan. "We are pleased to present the interim data from the uncommon non-ex20ins EGFR mutations cohort from the REZILIENT2 trial, potentially demonstrating the need for novel, targeted therapeutic approaches for this patient population."

Authors reported results from the REZILIENT1 study of zipalertinib from the cohort of NSCLC patients with EGFR ex20ins mutations who received prior amivantamab therapy1

Summary of Efficacy – by Blinded Independent Central Review (BICR):
As of the June 2025 data cutoff, 84 post-amivantamab patients were enrolled in REZILIENT1 and received at least one dose of 100 mg zipalertinib. Patients had received a median of 3 prior lines of therapy, and 54.8% of patients had a history of brain metastases.

With follow-up of more than 9 months, zipalertinib demonstrated:

In all patients (n=84), confirmed objective response rate (ORR) was 27.4% with median duration of response (mDOR) of 8.5 months, and the disease control rate (DCR) was 84.5%.

In patients with prior amivantamab only (n=54), ORR was 31.5% with mDOR of 9.5 months, and the DCR was 87.0%.

In patients with prior amivantamab and other ex20ins-targeted therapy (n=30), ORR was 20.0% with mDOR of 8.3 months, and the DCR was 80.0%.

In patients with brain metastases who received prior amivantamab only (n=31), the systemic ORR was 29%.
Summary of Safety and Tolerability
The safety analysis population included all post-amivantamab patients in REZILIENT1 who received at least one dose of 100 mg zipalertinib (n=84). The results showed that zipalertinib 100 mg twice daily demonstrated a manageable safety profile in patients who progressed on prior chemotherapy and amivantamab with no new safety signals.

The most common treatment-emergent adverse events (TEAEs, all-grade) were paronychia (41.7%), anemia (38.1%), rash (34.5%), nausea (28.6%), diarrhea (22.6%), dry skin (21.4%), dermatitis acneiform (21.4%) and dyspnea (20.2%).

The most common grade ≥3 TEAEs were anemia (15.5%), pneumonia (10.7%), dyspnea (6.0%), rash (3.6%), diarrhea (2.4%) and stomatitis (2.4%).

Authors reported results from the REZILIENT2 study of zipalertinib from the cohort of patients with NSCLC harboring uncommon non-exon 20 insertion EGFR mutations2

Summary of Preliminary Efficacy –by Investigator
As of the March 2025 data cutoff, 40 patients were enrolled in the REZILIENT2 Cohort D and received zipalertinib 100 mg orally twice daily. Previously treated patients had received a median of 2 prior lines of therapy, and 30% of all patients enrolled, including treatment-naïve, had a history of brain metastases.

As of the data cut-off, zipalertinib demonstrated:

In the overall efficacy population (n=40), confirmed ORR was 30% with a mDOR of 7.75 months, and the disease control rate (DCR) was 70%.
In the treatment-naïve population (n=8), ORR was significantly higher (62.5%) compared to the previously treated patient population (n=32, ORR 21.9%).
Summary of Preliminary Safety and Tolerability
The safety analysis population included all REZILIENT2 patients in Cohort D who received at least one dose of 100 mg zipalertinib (n=40). The results showed that zipalertinib 100 mg twice daily demonstrated a manageable safety and tolerability profile with no new safety signals.

The most common treatment-related adverse events (TRAEs, all-grade) were paronychia (47.5%), dermatitis acneiform (37.5%), stomatitis (32.5%), anemia (30.0%), diarrhea (22.5%), rash (20.0%), and dry skin (15.0%). The majority of TRAEs were grade 1 or 2.

The most common grade ≥3 TRAEs were paronychia (5.0%), pneumonitis and anemia (5.0%).

About REZILIENT1
REZILIENT1 (Researching Zipalertinib In EGFR Non-Small Cell Lung Cancer Tumors) is a Phase 1/2 clinical trial (NCT04036682) to evaluate efficacy and safety of zipalertinib in adult patients with advanced or metastatic NSCLC harboring EGFR ex20ins mutations who have received prior therapy. Patients were treated with oral zipalertinib 100 mg twice daily. The primary endpoints were ORR and DOR as assessed by blinded independent central review (ICR) per RECIST v1.1. Adverse events were characterized and graded according to Common Terminology Criteria for Adverse Events (CTCAE v5.0).

About REZILIENT2
REZILIENT2 is a Phase 2b clinical trial (NCT05967689), evaluating zipalertinib in patients with locally advanced/metastatic NSCLC harboring ex20ins and uncommon single or compound EGFR mutations. Patients were treated with oral zipalertinib 100 mg twice daily. The primary endpoint was ORR and confirmed per investigator-assessed Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 and the secondary endpoints included DOR, DCR and safety.

About Zipalertinib
Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with ex20ins mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib has received Breakthrough Therapy Designation from the FDA. Zipalertinib is investigational and has not been approved by any health authority.

Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

On September 9, 2025 bioAffinity Technologies, Inc. (Nasdaq: BIAF; BIAFW), a biotechnology company advancing noninvasive diagnostics for lung cancer and other lung diseases, reported another compelling case study in which its flagship product, CyPath Lung, identified cancer in a patient with an incidental finding of ground-glass lung nodules (Press release, BioAffinity Technologies, SEP 9, 2025, View Source [SID1234655874]).

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Ground-glass nodules appear in imaging as hazy gray areas distinct from solid nodules. Clinicians often find them challenging to assess because they can remain stable for many years, often mimic benign lesions caused by inflammation or fibrosis, and typically do not light up on PET scans.

"Society guidelines for ground-glass nodules recommend two to five years of watchful waiting with serial CT scans. Obviously, this can put both patients and their doctors in an uncomfortable position of balancing uncertainty against the risks of delayed diagnosis," said Gordon Downie, MD, PhD, bioAffinity Technologies’ Chief Medical Officer. "Adding CyPath Lung to the traditional standard of care can provide actionable results that move beyond watchful waiting to timely, potentially life-saving treatment."

The patient, a 66-year-old former smoker, underwent a CT scan for abdominal pain, suspecting kidney stones. The scan incidentally captured a ground-glass nodule in her lung, and a subsequent CT scan of the chest found multiple ground-glass nodules, the largest 13 mm in length. Because of her smoking history, she was referred to a lung clinic for evaluation and risk stratification. Her physician ordered the CyPath Lung test, which returned a "likely malignant" result. Based on the positive CyPath Lung test, the care team proceeded with robotic bronchoscopy. Pathology confirmed lung cancer, and the patient was referred for surgical treatment.

"This case provides another real-world example of CyPath Lung’s value in the evaluation of both solid and sub-solid lung nodules by providing actionable information in real time that can help direct next steps in care, reduce uncertainty and improve patient outcomes," bioAffinity Technologies President and CEO Maria Zannes said. "CyPath Lung has the potential to significantly reduce the mystery of sub-solid, or ground-glass, nodules when they show up on imaging, and both patient and physician are reluctant to delay diagnosis."

About CyPath Lung

CyPath Lung uses proprietary advanced flow cytometry and artificial intelligence (AI) to identify cell populations in patient sputum that indicate malignancy. Automated data analysis helps determine if cancer is present or if the patient is cancer-free. CyPath Lung incorporates a fluorescent porphyrin that is preferentially taken up by cancer and cancer-related cells. Clinical study results demonstrated that CyPath Lung had 92% sensitivity, 87% specificity and 88% accuracy in detecting lung cancer in patients at high risk for the disease who had small lung nodules less than 20 millimeters. Diagnosing and treating early-stage lung cancer can improve outcomes and increase patient survival. For more information, visit www.cypathlung.com.

On September 9, 2025 iOnctura, a clinical-stage precision oncology company focused on neglected and hard-to-treat cancers, reported the expansion of its clinical trial program for lead candidate roginolisib into the United States (Press release, iOnctura, SEP 9, 2025, View Source [SID1234655888]). Several US trial sites are now enrolling patients in the OCULE-01 Phase II study in metastatic uveal melanoma, with an additional study, led by Dr Jennifer Brown, underway in chronic lymphocytic leukemia (CLL) at Dana-Farber Cancer Institute.

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Catherine Pickering, CEO and co-founder of iOnctura said, "We are proud to begin the next phase of iOnctura’s global growth by making roginolisib available to US patients in our clinical studies. The enthusiastic response from US investigators, leading research centers, and patient communities highlights the significant opportunity to impact outcomes for individuals with limited treatment options."

Roginolisib, an orally dosed small molecule allosteric modulator of PI3Kδ, is being investigated in multiple randomized Phase II studies in solid and hematological malignancies. The global Phase II randomized OCULE-01 study (NCT06717126) will assess whether roginolisib improves overall survival in patients with metastatic uveal melanoma who have progressed on prior therapy. Patients from both the US and Europe are now being treated in the study, which started in March 2025.

Roginolisib is also being investigated in patients with non-small cell lung cancer (NSCLC) (NCT06879717) and myelofibrosis (NCT06887803). In these diseases, targeting the PI3Kδ pathway in combination with standard therapies has potential to reverse resistance[1],[2].

Seeing the promise of roginolisib as a combination therapy, the US Department of Defense (DoD) recently awarded a substantial grant to Dr. Jennifer Brown at Dana-Farber Cancer Institute in Boston, MA, to explore the potential of roginolisib in relapsed / refractory CLL in a Phase I / II study (NCT06644183).

Dr. Jennifer R Brown, M.D. Ph.D., Director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and Principal Investigator on the study and grant said, "We are enthusiastic about the potential of roginolisib in enhancing treatment outcomes for CLL patients who have relapsed after prior Bruton’s tyrosine kinase inhibitor therapy. We feel roginolisib offers a promising avenue to improve remission depth and duration in combination with venetoclax and rituximab, whilst minimizing treatment-related side effects."

Recently published preclinical evidence by Sasi, Tarantelli et al. supports the synergistic potential of roginolisib and venetoclax in the treatment of CLL[3].