On December 11, 2024 BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) ("BriaCell" or the "Company"), a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care, reported its impressive survival and clinical benefit data in MBC patients, including those with CNS metastases, treated with the Bria-IMT plus CPI regimen (Press release, BriaCell Therapeutics, DEC 11, 2024, View Source [SID1234649127]). The data is featured in BriaCell’s "Spotlight" poster presentation session, at the 2024 San Antonio Breast Cancer Symposium (SABCS ) held at Henry B. Gonzalez Convention Center, San Antonio, TX.

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"Metastatic breast cancer remains an essentially incurable disease, with a significant unmet medical need in patients who are relapsed/refractory to recently approved therapies such as CPIs and antibody-drug conjugates (ADCs)," stated Dr. William V. Williams, BriaCell’s President & CEO. "We are very pleased with the Bria-IMT combination regimen’s tolerability profile, and most importantly its outstanding clinical activity in heavily pre-treated patients who failed other therapeutic options."

"In addition to our striking survival data in MBC patients, we are excited by potential biomarkers for early identification of patients who would benefit from treatment with the Bria-IMT combination regimen," noted Giuseppe Del Priore, MD, MPH, BriaCell’s Chief Medical Officer. "We expect to replicate Phase 2’s impressive survival and clinical benefit data in our ongoing pivotal Phase 3 study."

"While CNS metastatic disease has historically had a very poor prognosis, our clinical data to date, shows solid survival and clinical benefit in patients with CNS metastasis," stated Sailaja Kamaraju, MD, Assistant Professor of Medicine at the Medical College of Wisconsin, Division of Hematology and Oncology. "We are optimistic that the Bria-IMT combination regimen, with its unique targeted mechanism of action, may be able to produce meaningful clinical and survival benefits in other cancer patients with CNS metastases who have lost hope with little to no other therapeutic options."

The data presented is from the fully enrolled BriaCell Phase 2 combination study of Bria-IMT plus CPI.

An aggregate of 54 MBC patients were enrolled in the study – all treated with the Bria-IMT combination regimen {11 patients received KEYTRUDA (pembrolizumab), and 43 patients received Incyte’s retifanlimab with one patient cross over from the KEYTRUDA study to retifanlimab}. Data is available on all 54 of these heavily pre-treated metastatic breast cancer patients (average number of prior treatments = 6). Of these 54 patients, 37 were treated with the formulation currently under investigation in BriaCell’s ongoing pivotal Phase 3 study in metastatic breast cancer (listed on ClinicalTrials.gov as NCT06072612 ). Final median overall survival calculation for the patients in the Phase 2 portion of the study is pending, as most of these patients remain alive over 1 year following their start on the study. No Bria-IMT related discontinuations have been reported to date.

The details about the Spotlight presentation and other poster sessions are as follows:

Abstract Number: SESS-1071 (Spotlight Poster)
Title: Overall survival results of Bria-IMT allogenic whole cell-based cancer vaccine
Time: Wednesday, December 11, 2024 7:00 AM – 8:30 AM CST
Presentation ID: PS3-06

Bria-IMT regimen’s impressive OS and tolerability in MBC patients

Median overall survival (OS) to date of 13.4 months for Phase 2 patients treated with the Phase 3 formulation (15.6 months for those treated since 2022 with the Phase 3 formulation) double that of comparable patients in the literature (Cortes J, et al. Annals of Oncology 2018; Kazmi S, et al. Breast Cancer Res Treat. 2020; O’Shaughnessy J et al. Breast Cancer Res Treat. 2022; Tripathy D, et al. JAMA Oncol. 2022; Bardia A, et al. J Clin Oncol. 2024)
Final Phase 2 OS calculation is pending as many patients remain alive well over 1 year after starting the study
Median overall survival (OS) for patients who received the Phase 3 formulation in the Phase 2 portion of the study who also developed an immune response to the vaccine as measured by delayed-type hypersensitivity (DTH) not yet reached with >1 year follow-up
13.7 months median OS in MBC patients with central nervous system (CNS)/intracranial tumors treated with the Bria-IMT regimen with or without a CPI
Objective response rates (ORR) and clinical benefit rates (CBR) were observed across all MBC patient subsets, but positive clinical outcomes were more prominent in HER2+ and HR+/HER2- patient subsets
Bria-IMT regimen was well-tolerated and produced clinical benefit in heavily pretreated MBC patients
Patients who developed a DTH response had lower neutrophil to lymphocyte ratio (NLR), suggesting improved clinical benefit in these patients
Delayed-type hypersensitivity (DTH) response, and circulating tumor cells (CTC) levels were significantly different between patients who responded vs those who did not respond to the Bria-IMT combination regimen
In conclusion, clinical findings to date support the potential safety and efficacy of Bria-IMT, along with its potential use in CNS metastases, as well as the possible use of biomarkers to predict clinical outcomes in BriaCell’s ongoing pivotal Phase 3 study in MBC.

Abstract Number: SESS-1431
Title: Identification of antigenic determinants in SV-BR-1 derived cellular breast cancer vaccines
Time: Wednesday, December 11, 2024 5:30 – 7:00 PM CST
Presentation ID: P2-06-02

Summary:
BriaCell successfully identified immunogenic (i.e. immune system activating) peptides in patients treated with Bria-IMT, a cell-based cancer vaccine, and showed Bria-IMT’s ability to produce a targeted immune response against tumor antigens.

Key immunogenic peptides detected included those with post-translational modifications (PTMs), such as citrullination and cysteinylation, an important type of neoantigen that may be shared across many patients with cancer
Highlighted the advantage of cell-based cancer vaccines over RNA and peptide-based vaccines including their ability to present a broad and diverse repertoire of antigens (i.e. both conventional and unconventional types)
Cell-based cancer vaccines also display unknown, patient-specific neoantigens that are hard to reproduce with RNA or peptide vaccines
Diverse antigen presentation produces a robust, polyclonal immune response, engaging both CD8+ and CD4+ T cells against multiple tumor target
In conclusion, scientific data presented suggests that the unique mechanism of cell-based cancer vaccines may reduce cancer cells’ immune escape and may potentially lead to strong and long-lasting clinical outcomes in cancer patients.

Abstract Number: SESS-2217
Title: PD-L1 upregulation in circulating tumor associated cells predicts for clinical outcomes in a phase I/II clinical trial using SV-BR-1-GM vaccine with the checkpoint inhibitor retifanlimab in metastatic breast cancer patients, an interim analysis
Time: Wednesday, December 11, 2024 12:00 – 2:00 PM CST
Presentation ID: P1-01-17

Summary:
Interim analysis after at least one year of Bria-IMT plus CPI regimen shows the following:

Significantly lowered levels of circulating tumor cells (CTCs) and cancer associated macrophage-like cells (CAMLs) in 40% of heavily pre-treated MBC patients
Lower CTCs/CAMLs levels were significantly correlated with better survival outcomes (i.e. better PFS and trended for better OS)
Bria-IMT appeared to increase PD-L1 levels in 15 patients which correlated with better clinical responses to combination treatment with the anti-PD-1 check point inhibitor retifanlimab
In conclusion, clinical data support the combination regimen in our ongoing pivotal Phase 3 study and suggests CTCs and CAMLs and PD-L1 levels may be relevant indicators of clinical outcome in MBC patients treated with Bria-IMT plus CPI.

Abstract Number: SESS-1068
Abstract Title: ASTRO-VAC CNS: Bria-IMT in the management of tumor agnostic metastatic CNS lesions
Time: Wednesday, December 11, 2024 5:30 – 7:00 PM CST
Presentation ID: P2-10-24

Results: The poster provides the details of a planned Phase 2 study design expanding the use of Bria-IMT + CPI to tumor agnostic cancer patients (i.e. kidney cancer, brain cancer, etc.) with central nervous system (CNS) metastasis.

To view the posters, please visit View Source

On December 11, 2024 The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group focused on bringing transformational oncology treatments to cancer patients, along with MEDSIR, a leading global independent clinical research company in oncology and part of Oncoclínicas & Co., the largest specialized oncology treatment group in Latin America, reported research on the pioneering clinical trial ADELA (Press release, Menarini, DEC 11, 2024, View Source [SID1234649063]). This important research addresses therapeutic resistance in advanced ER+/HER2- breast cancer. Presented at the San Antonio Breast Cancer Symposium 2024 (SABCS), the study represents a key milestone in the quest for more effective and personalized treatment options for patients with disease progression.

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The standard first-line treatment for advanced ER+/HER2- breast cancer combines endocrine therapy with CDK4/6 inhibitors. ESR1 mutations develop as a result of prior exposure to endocrine therapy during metastatic treatment, and up to 50% of ER+, HER2- advanced or metastatic breast cancers will develop these mutations. ESR1 mutations cause the tumors to become resistant to endocrine therapy, in turn causing the cancer to progress; therefore, it is important to test for ESR1 whenever mBC progresses. Longer exposure to endocrine therapy during first-line treatment increases the chance of a patient’s tumor developing an ESR1 mutation. With the goal of addressing this unmet medical need, the ADELA phase III clinical trial investigates a new therapeutic option combining elacestrant, a next generation, oral selective estrogen receptor degrader, with everolimus, an mTORC1 inhibitor.

This combination is being evaluated in patients with advanced ER+/HER2- breast cancer that harbors ESR1 mutations, and who have experienced progression after standard first-line treatment. Results from the phase III EMERALD study were the basis for elacestrant’s approval. Meanwhile, everolimus has shown efficacy in inhibiting other resistance mechanisms in this type of cancer. The elacestrant and everolimus combination has demonstrated preliminary efficacy with a manageable safety profile in the phase 1b/2 ELEVATE study (NCT05563220).

"We at Menarini Stemline are delighted to announce the collaboration with MEDSIR to continue advancing the clinical research to explore the combination therapy with elacestrant," said Nassir Habboubi, MD, Chief Medical Officer of Stemline Therapeutics. "We are committed to driving innovation in cancer treatment by delivering transformational therapies aiming to extend the lives of people living with cancer."

The primary objective of this international, randomized, double-blind trial is to evaluate whether the combination of elacestrant and everolimus offers greater efficacy in delaying disease progression compared to elacestrant monotherapy. Additionally, it investigates other crucial aspects, such as overall survival, toxicity profile, and the impact on patients’ quality of life.

The ADELA study represents a critical step in understanding how to overcome tumor resistance challenges in patients with ESR1 mutations, with the goal of advancing towards more effective and safer treatments.

"At MEDSIR, we understand innovation not only as achieving clinical results but as the ability to transform patients’ lives on a global scale. With ADELA, we take a decisive step toward accomplishing less invasive and more accessible treatments, aiming to offer new hope to those facing the most complex forms of the disease. This advancement reinforces our commitment to increasingly personalized and patient-centered medicine, a fundamental pillar in shaping the future of oncology," said Dr. Antonio Llombart-Cussac, Senior Scientific Leader at MEDSIR.

The phase III study not only has significant clinical objectives, but also holds the potential to pave the way for regulatory approval of this therapeutic combination, enabling its use in a broader population of patients with advanced breast cancer. Moreover, the international scope of the study, which includes participation from multiple countries, including Spain, Italy, France, Austria, the Czech Republic, Greece, Germany, and the United Kingdom, underscores the study’s global importance and relevance in the scientific community.

The presentation of the ADELA study at an event as prominent as SABCS 2024 reinforces MEDSIR’s leadership in excellence-driven oncology research and highlights its focus on addressing unmet needs in breast cancer treatment. The ADELA study is active and already recruiting patients.

About ORSERDU (elacestrant)

U.S. Indication: ORSERDU (elacestrant), 345 mg tablets, is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

Full prescribing information for the U.S. can be found at www.orserdu.com.

Important Safety Information
Warning and Precautions

Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid profile prior to starting and periodically while taking ORSERDU.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the final dose.

Adverse Reactions

Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).
The most common adverse reactions (≥10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite(15%), diarrhea(13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%).

Drug interactions

Concomitant use with CYP3A4 Inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU.

Use in specific populations

Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.
Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B).
The safety and effectiveness of ORSERDU in pediatric patients have not been established.

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

On December 11, 2024 CatalYm reported that data of the first-in-human Phase 1/2a study of its lead drug candidate visugromab were published in Nature (Press release, Catalym, DEC 11, 2024, View Source [SID1234649062]). The paper titled "Neutralizing GDF-15 can overcome anti-PD-(L)1 resistance in solid tumors" emphasizes the significant potential of visugromab to induce unprecedented cancer remission depth and durability across multiple solid tumor indications as well as in combination with nivolumab in late- to last-line solid tumors. Visugromab is a humanized, monoclonal antibody that counteracts GDF-15, a critical immunosuppressant used by tumor cells to survive.

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The publication provides a mature data set of the GDFATHER Phase 1/2a trial (NCT04725474), demonstrating that the company’s anti-GDF-15 antibody visugromab in combination with the PD-1-inhibitor nivolumab delivers deep and durable responses in by strict RECIST 1.1 criteria anti-PD-(L)1 relapsed/refractory solid tumor patients. Building on interim data presented at ASCO (Free ASCO Whitepaper) earlier this year, the additional findings extend the durability profile of the anti-tumor responses seen in these late- to last-line metastatic non-small cell lung cancer (NSCLC), urothelial cancer (UCC) and hepatocellular cancer (HCC) patients. The publication further provides a wealth of translational research data that demonstrate the detailed proof-of-mechanism (POM) for visugromab, which induces T-cell influx, T-cell proliferation, and Interferon-γ signature induction in the tumor microenvironment both in monotherapy and in combination with nivolumab. Furthermore, pan-cancer immunogenomic analyses demonstrate the impact of GDF-15 on the tumor microenvironment and its immune cell landscape.

The full publication can be accessed and downloaded via the following link.

"The publication of our data in Nature confirms the high significance and novelty the scientific community has ascribed to GDF-15 as an immuno-oncology target, as well as the potential of visugromab to transform the cancer immunotherapy treatment landscape," said Eugen Leo MD PhD MBA, Chief Medical Officer at CatalYm. "We observed both robust proof-of-mechanism and clinical proof-of-concept in this first-in-human trial for visugromab, with more than half of our responders achieving deeper RECIST 1.1 responses than seen with their initial checkpoint inhibitor treatment. Notably, we see a growing number of lasting complete responses in late- to last-line patients who had no further therapeutic alternatives anymore. This is a significant outcome not seen with other exploratory I/O treatments in this setting. We are now rapidly advancing visugromab into earlier lines of treatment, with several trials planned for 2025 in high unmet medical need solid tumor indications."

Summary of Key Clinical Results from the ongoing GDFATHER Phase 1/2a trial (GDF-15 Antibody-mediaTed Human Effector T Cell Relocation Phase 1/2a Trial):

The matured results from the Phase 2a indication-specific cohorts for NSCLC, UC, and all HCC so far treated show the following Objective Response Rates (ORR) based on strict RECIST 1.1 criteria:
non-squamous NSCLC: ORR of 19.0% (4/21), with 2 partial responses (PR) and 2 complete responses (CR)
UC: ORR of 18.5% (5/27), with 4 PR and 1 CR
HCC: interim ORR of 20.0% (4/20), with 3 PR and 1 CR
The current mean duration of response (DoR) for UC and NSCLC surpassed 15 and 16 months with 7/9 responses ongoing.
More than half of all responders in the NSCLC and UC cohorts of the trial experienced a response depth on study treatment as per RECIST 1.1 criteria that had not been reached on their prior anti-PD1/PD-L1 treatment that was mostly administered as first-line treatment and in combination with chemotherapy.
Among the NSCLC and UC responders, 3 out of 4 complete responders had not achieved a complete response on any prior line of systemic treatment, including their initial anti-PD1/PD-L1 therapy.
Additionally, biomarker analyses revealed promising potential for patient stratification, with elevated levels of serum GDF-15 correlating with reduced immune cell infiltration in tumors.
The combination of visugromab with nivolumab was overall well-tolerated, with a safety profile comparable to nivolumab treatment alone.
In a subgroup of patients that had combined manifest cachexia, a similar effect on weight gain was observed as demonstrated for another GDF-15 inhibitor in a recent cachexia trial.
Cachexia, a syndrome characterized by severe weight loss and muscle wasting is driven by elevated GDF-15 levels in certain cancer types. By neutralizing GDF-15, visugromab can help mitigate these effects, potentially improving the quality of life for patients undergoing intensive cancer treatments.

Based on these encouraging data, CatalYm is currently preparing for a broad Phase 2b program in earlier treatment settings for non-squamous NSCLC and additional tumor indications. These developments highlight the company’s commitment to tackling cancer resistance and improving treatment outcomes for patients across multiple tumor types.

About Visugromab (CTL-002)

Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by reenabling immune cell activation, proliferation and Interferon-γ signature induction. Visugromab has demonstrated a good safety profile and potent and durable anti-tumor efficacy in combination with anti-PD-1 treatment in advanced cancer patients. The antibody will now be investigated in Phase 2b studies in multiple solid tumor indications.

On December 11, 2024 SystImmune, Inc. (SystImmune), a clinical-stage biotechnology company, reported that a poster for BL-B01D1, a potentially first-in-class EGFRxHER3 bispecific antibody drug conjugate (ADC) will be presented at the San Antonio Breast Cancer Symposium (SABCS) 2024, taking place on December 10-13 in San Antonio, Texas. BL-B01D1 is being jointly developed by SystImmune and Bristol Myers Squibb under an exclusive license and collaboration agreement (Press release, SystImmune, DEC 11, 2024, View Source [SID1234649061]).

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Updated results from clinical trials of BL-B01D1 will include data from patients with advanced stage triple-negative, HR-positive / HER2-negative, and HER2-positive breast cancer. The data to be presented at SABCS highlights continued progress of BL-B01D1 clinical development and builds upon the previously reported clinical data in lung, breast and bladder cancer patients.

"These data substantially add to the body of evidence that shows encouraging signals of efficacy in main breast cancer subtypes and strengthens our conviction that BL-B01D1 has a manageable safety profile," said Jonathan Cheng, M.D., CMO of SystImmune. "We are committed to continuing the development of this therapy through clinical trials and exploring its potential both as a monotherapy and in combination with other agents, to improve outcomes for cancer patients globally."

Details on the presentations at SABCS are below:
‍BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate, in patients with Locally Advanced or Metastatic Breast Cancer and other Solid Tumor: Updated results from a Phase I study
Presentation Number: P5-07-27/Abstract SESS-630
Speaker: Jiong Wu, M.D.
Onsite Poster display date: Friday, December 13th, 2024

About BL-B01D1
The company is developing BL-B01D1, a bispecific antibody-drug conjugate (ADC) that targets both EGFR and HER3. These proteins are highly expressed in most epithelial tumors. The tetravalent BL-B01D1 has two binding domains for distinct Growth Factor Receptors that drive cancer cell proliferation and survival. Inheriting the SI-B001 mechanisms of action, BL-B01D1 blocks EGFR and HER3 signals to cancer cells, reducing proliferation and survival signals. Upon antibody mediated internalization, BL-B01D1 is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induces genotoxic stress activating pathways leading to cancer cell death.

On December 11, 2024 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported the publication of a pooled analysis evaluating sunvozertinib in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI)-resistant non-small cell lung cancer (NSCLC) in the official journal of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Lung Cancer (Press release, Dizal Pharma, DEC 11, 2024, View Source [SID1234649060]). The results of the analysis demonstrated that sunvozertinib exhibited promising antitumor activity and favorable safety profile, warranting future investigations into its potential in patients with EGFR mutated NSCLC who have developed resistance to EGFR TKIs.

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The analysis pooled data from three Phase 1 and 2 studies (WU-KONG1, WU-KONG2 and WU-KONG15). A total of 40 NSCLC patients with EGFR sensitizing mutations who had developed resistance to EGFR TKI treatment were enrolled, 90% of whom had received ≥ 3 prior lines of therapy. Eligible patients received sunvozertinib at doses ranging from 50 mg to 400 mg once daily. As of September 15, 2023, the key findings of the analysis were as follows:

The best objective response rate (ORR) was 27.5 %, and disease control rate (DCR) was 60 %.
The median duration of response (mDoR) and progression free survival (mPFS) were 6.5 months and 6 months, respectively.
Greater ORR of 55.6% was seen in patients with EGFR sensitizing and T790M double mutations (78% had received third-generation EGFR-TKI treatment in prior lines of therapy).
Sunvozertinib was well-tolerated, and the safety profile was consistent with previous reports.
"Resistance to chemotherapy or EGFR TKIs remains a major challenge in the management of EGFR mutated NSCLC. In clinical practice, EGFR-targeted therapeutic strategies are one of the main approaches to addressing EGFR-TKI resistance," said Mengzhao Wang, MD, PhD, at Peking Union Medical College Hospital, the first and corresponding author of the paper. "Sunvozertinib is an oral, irreversible EGFR TKI that targets a broad spectrum of EGFR mutations while maintaining high selectivity for wild-type EGFR. Previous studies suggested that sunvozertinib demonstrated anti-tumor activity in NSCLC patients with EGFR-sensitizing mutations, T790M mutations, and exon 20 insertion mutations. This new analysis further validated sunvozertinib’s potential in overcoming resistance to prior EGFR TKI treatments, warranting further investigation."

"Encouragingly, the pooled analysis has revealed the potential clinical value of sunvozertinib in EGFR TKI-resistant NSCLC," said Xiaolin Zhang, PhD, CEO of Dizal. "Confronted with the challenge of resistance to third-generation EGFR TKIs, we will continue to advance our exploration in this area, aiming to bring new treatment options to patients with EGFR mutated NSCLC."

About sunvozertinib (DZD9008)
Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA to treat advanced NSCLC with EGFR exon20ins after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. The primary endpoint of the study was the confirmed overall response rate (cORR) as assessed by the Independent Review Committee (IRC) reached 60.8%. Anti-tumor efficacy was observed across a broad range of EGFR exon20ins subtypes, and in patients with pretreated and stable brain metastasis. In addition, sunvozertinib also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M, and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 exon20ins.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug-related TEAEs (treatment-emergent adverse event) were Grade 1/2 in nature and clinically manageable.

Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 Part B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR exon20ins.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery and The Lancet Respiratory Medicine.