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].

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 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 Tagworks Pharmaceuticals BV ("Tagworks"), a clinical-stage precision oncology company using its proprietary Click-to-Release treatment platform to develop a new standard of care for patients suffering from solid tumors, reported the third dose level has been initiated in the ongoing Phase 1 clinical trial evaluating TGW101, a first-in-class antibody-drug conjugate (ADC) targeting tumor associated glycoprotein 72 (TAG-72) with a monomethyl auristatin E (MMAE) payload, in patients with advanced solid tumors (Press release, Tagworks Pharmaceuticals, SEP 9, 2025, View Source [SID1234655885]).

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"We are pleased to report continued progress in our Phase 1 clinical trial of TGW101 which reflects our strong operational execution and commitment to advancing our pioneering Click-to-Release technology," said Ken Mills, Chief Executive Officer of Tagworks. "The Safety Oversight Committee’s decision to proceed to the third dose level highlights TGW101’s favorable safety profile to date. We are encouraged by the potential of TGW101’s highly differentiated profile to address significant unmet needs in the treatment of advanced solid tumors, while overcoming limitations seen with other ADC therapies. We look forward to sharing preliminary data from the study, including safety, pharmacokinetics, and potential early signs of clinical activity, in early to mid-2026."

The ongoing Phase 1 trial is a multicenter, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of TGW101 in patients with relapsed or refractory solid tumors. The primary objectives are to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and dose regimen for cohort expansion.

To date, the trial has initiated three dose levels following favorable safety reviews by the Safety Oversight Committee (SOC). Up to seven dose levels are currently planned, and the maximum dose to be evaluated may be updated based on evolving clinical safety and pharmacokinetic data. The study aims to enroll up to 50 patients across sites in the United States, with potential expansion to additional regions.

Tagworks expects to share preliminary safety and pharmacokinetic data, along with any early signals of efficacy, in early to mid-2026.

About TGW101
TGW101 is an antibody-drug conjugate (ADC) targeting TAG-72, a non-internalizing marker found on the surface of many solid tumor cells. TGW101 consists of a TAG-72-binding diabody conjugated with monomethyl auristatin E (MMAE) toxin. TGW101 is administered intravenous (IV) first and allowed to bind to TAG-72 in the tumor. Then a small molecule trigger is administered IV, resulting in selective chemical cleavage of the linker of the tumor-bound TGW101, release of the MMAE in the extracellular tumor microenvironment and diffusion into surrounding tumor cells. TGW101 is being studied in an open-label, multicenter, Phase 1 dose-escalation clinical trial designed to evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy in patients with advanced solid tumors.

On September 9, 2025 Citius Oncology, Inc. ("Citius Oncology") (Nasdaq: CTOR), the oncology-focused subsidiary of Citius Pharmaceuticals, Inc. ("Citius Pharma") (Nasdaq: CTXR), a late-stage biopharmaceutical company developing and commercializing first-in-class critical care products, reported that it has entered into a securities purchase agreement with a single institutional investor to purchase 5,142,858 shares of common stock in a registered direct offering (Press release, Citius Oncology, SEP 9, 2025, View Source [SID1234655884]). In a concurrent private placement, the Company also agreed to issue unregistered warrants to purchase up to an aggregate of 5,142,858 shares of common stock. The combined effective offering price for each share of common stock and accompanying warrant is $1.75. The warrants will have an exercise price of $1.84 per share, will be exercisable six months from the date of issuance, and will expire on the five and one-half year anniversary from the date of issuance.

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The gross proceeds to the Company from the registered direct offering and concurrent private placement are estimated to be approximately $9.0 million before deducting placement agent fees and other estimated offering expenses payable by the Company. The offering is expected to close on or about September 10, 2025, subject to the satisfaction of customary closing conditions.

Maxim Group LLC is acting as sole placement agent in connection with the offering.

The shares of common stock described above are being offered pursuant to a registration statement on Form S-3 (File No. 333-289979), which was filed with the U.S. Securities and Exchange Commission ("SEC") on September 2, 2025, and was declared effective by the SEC on September 4, 2025. The offering of shares of common stock will be made only by means of a prospectus supplement, forming a part of the effective registration statement. A prospectus supplement relating to the shares of common stock will be filed with the SEC. Electronic copies of the prospectus relating to this offering, when available, may also be obtained from Maxim Group LLC, 300 Park Avenue, 16th Floor, New York, New York 10022, Attention: Syndicate Department, by telephone at (212) 895-3745 or by email at [email protected]. The warrants to be issued in the concurrent private placement and the shares issuable upon exercise of such warrants were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and have not been registered under the Act or applicable state securities laws.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.