On September 9, 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 a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting, held November 6-10, 2024, in Houston, TX (Press release, BriaCell Therapeutics, SEP 9, 2024, View Source [SID1234646424]).

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"We are thrilled to be invited to present our data at this prestigious conference," stated Miguel Lopez-Lago, PhD, BriaCell’s Chief Scientific Officer. "We look forward to continuing our investigations of novel targeted immunotherapy candidates in clinical studies with the goal of making a positive contribution to the lives of breast cancer and prostate cancer patients."

The details about the presentation and session Information are as follows:

Location: Exhibit Halls A B George R. Brown Convention Center, Houston, TX
Date and Time: Friday, Nov. 8, 2024, 9:00 am -7:00 pm CST

Following the presentation, a copy of the poster will be posted on View Source

On September 9, 2024 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported completion of the first cohort of the Phase 2 STARBORN-1 trial evaluating TARA-002, an investigational cell-based immunopotentiator, for the treatment of pediatric patients with lymphatic malformations (LMs) (Press release, Protara Therapeutics, SEP 9, 2024, https://ir.protaratx.com/news-releases/news-release-details/protara-therapeutics-announces-completion-first-cohort-phase-2 [SID1234646439]). Enrollment is now underway in additional cohorts.

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"The initial data is compelling and reflective of the significant benefit observed in previous studies with OK-432, the predecessor of TARA-002," said Nancy Bauman, MD, Children’s National Medical Center: Children’s Research Institute, Washington DC, and investigator for the STARBORN-1 trial. "There is a pressing need for an effective therapeutic option for LMs, a rare condition mainly affecting children for which there are currently no U.S. FDA approved agents. I remain excited about the potential for TARA-002 to play a meaningful role in the treatment of these patients and look forward to future learnings from this important study."

Of three patients treated in the first cohort, which enrolled individuals six years to less than 18 years of age, two patients treated with TARA-002 achieved a complete response after receiving one dose of TARA-002; the responses were seen in a patient with a macrocystic lymphatic malformation and a patient with a ranula. The safety and tolerability seen in this cohort was consistent with that of the historical experience with OK-432 and included treatment emergent adverse events (TEAEs) of pain, swelling, fatigue, and body temperature increases. All TEAEs were mild to moderate and resolved.

"We are pleased with the progress of our Phase 2 STARBORN-1 trial and the encouraging results we have seen thus far," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "We have received positive feedback from our investigators and already have a number of patients on waiting lists for our subsequent cohorts, and expect to share initial results from our next cohort in the first half of 2025."

STARBORN-1 is a Phase 2 single-arm, open-label, prospective clinical trial evaluating the safety and efficacy of intracystic injection of TARA-002 for the treatment of macrocystic and mixed cystic LMs (≥ 50% macrocystic disease) in participants six months to less than 18 years of age. The trial will enroll approximately 30 patients including age de-escalation safety lead-in cohorts of children ages six years to less than18 years, two years to less than six years, and six months to less than two years, who will receive up to four injections of TARA-002 spaced approximately six weeks apart.

The primary endpoint of the trial is the proportion of participants with macrocystic and mixed cystic LMs who demonstrate clinical success, defined as having either a complete response (90% to 100% reduction from baseline in total LM volume) or substantial response (60% to less than 90% reduction in total LM volume) as measured by axial imaging.

About TARA-002 in LMs

TARA-002 is an investigational cell therapy based on the broad immunopotentiator, OK-432, which was originally granted marketing approval by the Japanese Ministry of Health and Welfare as an immunopotentiating cancer therapeutic agent. This cell therapy is currently approved in Japan and Taiwan for LMs and has been used to successfully treat thousands of pediatric patients with this rare condition. In addition, OK-432 was studied in the largest ever conducted Phase 2 trials in LMs, in which the therapy was administered via a now-closed compassionate use program led by the University of Iowa.

TARA-002 has been granted Rare Pediatric Disease designation by the U.S. Food and Drug Administration (FDA) for the treatment of LMs.

About Lymphatic Malformations

Lymphatic malformations (LMs) are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs are present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of three years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection; and cosmetic and other functional disabilities.

On September 9, 2024 Boehringer Ingelheim reported positive results from a Phase Ib primary analysis of Cohort 1 of the Beamion LUNG-1 trial evaluating zongertinib (BI 1810631) in pre-treated patients with advanced non-small cell lung cancer (NSCLC) with activating HER2 mutations (Press release, Boehringer Ingelheim, SEP 9, 2024, View Source [SID1234646455]). Zongertinib demonstrated a meaningful objective response rate and was generally well tolerated in the Cohort 1 setting. The results were presented in a Presidential Symposium at the IASLC 2024 World Conference on Lung Cancer (WCLC) and are included in the official 2024 WCLC Press Program.

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As of May 2024, 132 patients have been treated with 120 mg / 240 mg of zongertinib once a day (n=75/n=57). With a confirmed objective response rate (ORR) of 66.7%, 97.5% CI (53.8–77.5), (p<0.0001) as assessed by blinded independent central review (BICR), the primary endpoint was met for Cohort 1 (120 mg; n=75). Tumor shrinkage of any magnitude was observed in 94% of all patients across doses, per investigator assessment. The trial design includes a dose expansion that was carried out to find the optimal dose of zongertinib for this patient population. Patients were randomized 1:1 to either the 120 mg (n=58) or the 240 mg (n=55) group. After an interim futility analysis, 120 mg was selected as the dose to be evaluated further in Cohort 1, and 17 additional patients were enrolled. In the part of the trial where patients were randomized 1:1, zongertinib showed a response rate of 72.4% in patients treated with 120 mg daily, and 78.2% in patients treated with 240 mg daily as well as disease control rates (DCRs) of 95% and 100% respectively.

Phase Ib, Cohort 1 data also show preliminary brain activity with zongertinib. 33% (120 mg; n=27) and 40% (240 mg; n=25) of patients with asymptomatic brain metastases achieved confirmed objective response, with a DCR of 74% and 92% respectively, as per RANO-BM (recommendations for standardized tumor response and progression assessment) by BICR. The central nervous system is a common site of metastasis in NSCLC and is associated with poor prognosis and quality of life.2 Brain metastases are present in up to 30% of patients with NSCLC with activating HER2 mutations at diagnosis.3

"These new data could represent positive news in the future treatment of non-small cell lung cancer patients with activating HER2 mutations," said the trial’s principal investigator, Dr. John Heymach, MD, PhD, The University of Texas MD Anderson Cancer Center. "While these mutations are rare, they are critical drivers in a subset of non-small cell lung cancer cases, and current treatment options are severely limited. Patients with this type of cancer typically face a poor prognosis, with approximately 50% responding to first-line treatment and only 20% responding to second-line therapy." 4,5,6,7

Zongertinib is an investigational oral HER2 tyrosine kinase inhibitor (TKI) in development for patients with advanced NSCLC with activating HER2 mutations. Zongertinib was designed to spare wild-type EGFR thereby mitigating associated toxicities. Beamion LUNG-2, a global Phase III trial evaluating zongertinib compared to standard of care as first-line treatment in patients with advanced NSCLC with activating HER2 mutations is currently enrolling.

Paola Casarosa, Board of Managing Directors, Head of Innovation Unit at Boehringer Ingelheim, said: "Zongertinib’s efficacy and tolerability profile has the potential to become part of the future treatment landscape for patients with HER2 mutated lung tumors. Zongertinib is a perfect example of our approach to science in the discovery and development of novel treatments. Boehringer is committed to providing breakthrough therapies for cancer patients, and we look forward to advancing the zongertinib clinical program."

Zongertinib was generally well tolerated for 120 mg and 240 mg, with no deaths attributed to treatment and a low incidence of adverse events leading to dose reductions (11%) and discontinuation (3%). No new safety signals or treatment-related interstitial lung diseases (ILD) were observed, and Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 17% (120 mg) and 19% (240 mg) of patients treated with zongertinib. The most common TRAEs were Grade 1 or 2 diarrhea (43% and 11% respectively), Grade 1 or 2 rash (19% and 8% respectively).

Data are still maturing and with two thirds of responding patients still on treatment at data cut-off, progression-free survival (PFS) and duration of response (DoR) data will be reported at an upcoming conference.

About non-small cell lung cancer (NSCLC)
Lung cancer claims more lives than any other cancer type and the incidence is set to increase to over 3 million cases worldwide by 2040.8 NSCLC is the most common type of lung cancer.9 The condition is often diagnosed at a late stage,10 and fewer than 3 in 10 patients are alive five years after diagnosis.11 People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Up to 4% of lung cancers are driven by HER2 mutations (or gene alterations).12 Mutations in HER2 can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread.13

About zongertinib
Zongertinib (also known as BI 1810631) is an investigational oral HER2-specific tyrosine kinase inhibitor (TKI) that is being developed as a potential treatment for HER2 mutated non-small cell lung cancer (NSCLC). Zongertinib was granted FDA Fast Track Designation in 2023, then in 2024 it was granted Breakthrough Therapy Designation by the U.S. FDA and China CDE for the treatment of adult patients with advanced NSCLC whose tumors have activating HER2 mutations, and who have received a prior systemic therapy. HER2 is a member of the ErbB family of receptor tyrosine kinases (enzymes that act like chemical messengers).14 A recent study has shown pre-clinically that the investigational compound zongertinib has potential for further clinical study in HER2 dependent solid cancers as monotherapy and as concurrent treatment with ADC therapy or with KRAS-targeted drugs.14 Read more here.

About the Beamion clinical trial program
Beamion LUNG-1 (NCT04886804): An open-label, Phase I dose escalation trial, with dose confirmation and expansion, of zongertinib as monotherapy in people with advanced or metastatic solid tumors and NSCLC with activating HER2 mutations. The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumors with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with non-small cell lung cancer with a specific mutation in the HER2 gene. Beamion LUNG-2 is a phase 3, open label, randomized, active-controlled study that will enroll 270 patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring HER2 tyrosine kinase domain mutations to evaluate zongertinib compared with standard of care.

On September 8, 2024 Akeso (9926. HK) reported that its internally developed PD-1/VEGF bispecific antibody ivonescimab showed clinically significant results from a Phase II study, either as a monotherapy or in combination with chemotherapy, for the perioperative treatment of resectable non-small cell lung cancer (NSCLC) at the 25th World Conference on Lung Cancer (WCLC) (Press release, Akeso Biopharma, SEP 8, 2024, View Source [SID1234646408]). This marks ivonescimab’s third oral presentation at an international conference in 2024. Professor Zhao Xiaoliang from Tianjin Medical University Cancer Hospital delivered an oral presentation at WCLC, sharing China’s advancements in innovative cancer immunotherapies with global experts.

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As of February 2024, the AK112-205 study enrolled 60 patients, with 78.3% in stage III and 90% in N+ stage (Among N+ stage patients, 70% are in N2 stage). Of these, 49 underwent surgery (all R0 resections). The study results demonstrated that perioperative ivonescimab monotherapy or combined with chemotherapy for resectable NSCLC demonstrated high rates of pathological complete response (pCR) and major pathological response (MPR) in this phase II study.

Compared with ivonescimab monotherapy, rates of MPR and pCR in ivonescimab combined with chemotherapy were numerically higher, and across tumor stage and PD-L1 expression subgroups.

Ivonescimab + chemotherapy cohort: pCR rate was 43.6%, MPR rate was 71.8%. 69.2% of patients are with residual viable tumor (RVT) ＜ 5%.
As of Aug, 2024, 55 patients in this cohort completed surgery, pCR and MPR rates were improved to 52.7% and 72.7%, respectively. For squamous NSCLC, pCR and MPR rates were 63.6% and 84.1%, respectively.
Ivonescimab monotherapy cohort: pCR rate was 30.0%, MPR rate was 60.0%.
Event-Free Survival (EFS) is not mature yet. Related studies have point to a strong correlation between pCR and EFS.

The safety profile was manageable. There were no TRAEs that led to cancelled or delayed surgery or wound healing complications.

About Ivonescimab

Ivonescimab is a novel global first-in-class PD-1/VEGF bi-specific immunotherapy drug internally developed by Akeso. Ivonescimab has been approved in China for treating EGFR mutated locally advanced or metastatic non-squamous NSCLC patients who have progressed after EGFR TKI treatment. It is the world’s first approved bispecific antibody with a "cancer immunotherapy + anti-angiogenesis" synergistic mechanism.

Akeso out-licensed Summit Therapeutics exclusive rights to ivonescimab for the development and commercialization in certain territories including United States, Canada, Europe, Japan, Latin America, Africa and the Middle East. Ivonescimab is known as AK112 within Akeso and SMT112 in the territories licensed to Summit.

Currently, a Phase III study of ivonescimab monotherapy versus pembrolizumab monotherapy as first-line treatment for PD-L1+ NSCLC has met its primary endpoint of progression-free survival (PFS) in an interim analysis, achieving a decisive positive outcome. Based on this study, a supplemental New Drug Application (sNDA) for ivonescimab monotherapy as first-line treatment for PD-L1+ NSCLC has been submitted and granted priority review. Additionally, a Phase III clinical study of ivonescimab combined with chemotherapy versus tislelizumab combined with chemotherapy as first-line treatment for squamous NSCLC is ongoing. The HARMONi study, an international multicenter Phase III clinical study led by Akeso’s partner Summit, is investigating ivonescimab combined with chemotherapy for EGFR-mutated, locally advanced or metastatic nsq-NSCLC that has progressed after third-generation EGFR-TKI therapy. Another international multicenter Phase III study is comparing ivonescimab combined with chemotherapy to pembrolizumab combined with chemotherapy as first-line treatment for squamous NSCLC.

Furthermore, 3 new Phase III clinical studies are either initiated or about to start, including ivonescimab combined with AK117 (CD47) as first-line treatment for PD-L1 positive squamous cell carcinoma of the head and neck (vs. pembrolizumab), ivonescimab combined regimen as first-line treatment for cholangiocarcinoma (vs. durvalumab combined regimen), and ivonescimab combined regimen as first-line treatment for pancreatic cancer. Overall, ivonescimab is engaged in over 25 clinical trials across 17 indications, including lung cancer, pancreatic cancer, breast cancer, hepatocellular carcinoma, and colorectal cancer, through both monotherapy and combination therapy approaches.

On September 8, 2024 PRISM BioLab, Co. Ltd. ("PRISM"), a leading discovery and development biotechnology company designing small molecule inhibitors of protein-protein interaction (PPI) targets, reported that the interim analysis of a combination study of E7386(*1), created through collaboration research with Eisai Co., Ltd. ("Eisai"), and Lenvatinib mesylate ( "lenvatinib") (*2) will be presented by Eisai at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024, held in Barcelona, Spain from September 13 to 17, 2024 (Press release, Eisai, SEP 8, 2024, View Source [SID1234646409]). The abstract of the study has been released today.

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To determine the recommended dose of E7386 in combination with Lenvatinib in the open-label Phase Ib study(NCT0400879(*3)), expansion cohort of advanced endometrial cancer patients progressed following platinum-based chemotherapy and anti-PD-(L)1 immunotherapy have been implemented by Eisai. By data cutoff (Mar 7, 2024) in 16 patients, 31% (5 patients) showed the confirmed partial response (decrease of tumor size > 30%), and 31% (5 patients) showed the stable disease (tumor size -30% to +20%).

These results confirmed promising preliminary antitumor activity of E7386 + Lenvatinib with a manageable safety profile. To complete the study, enrollment to the expansion part is ongoing.

(*1) E7386

E7386 is an orally available small molecule CBP/ β-catenin inhibitor that inhibits protein-protein interactions between the transcription factor CBP and β-catenin, and regulates the Wnt signaling. E7386 achieved clinical POC (Proof of concept) in October 2021 and following clinical studies are ongoing including phase I for solid tumors as monotherapy, Phase Ib for solid tumors in combination with tyrosine kinase inhibitor Lenvatinib, Phase Ib/II for solid tumors in combination with pembrolizumab, the anti-PD-1 antibody from Merck & Co., Inc., Rahway, NJ, USA.

(*2) Lenvatinib

Lenvatinib is a multi-kinase inhibitor, discovered by Eisai and being co-developed and co-commercialized under a collaboration agreement with Merck & Co., Inc., Rahway, NJ, USA, which inhibits vascular endothelial growth factor receptors (VEGFRs),VEGFR1, VEGR2, VEGFR3 and fibroblast growth factor receptors (FGFRs), FGFR1, FGFR2, FGFR3, FGFR4, and other receptor tyrosine kinases, PDGFR-alpha, KIT, RET. Lenvatinib have been approved for thyroid cancer, hepatocellular carcinoma, thymic caner and renal cell carcinoma (in combination with Everolimus or pembrolizumab, the anti-PD-1 antibody from Merck & Co., Inc., Rahway, NJ, USA.). Lenvatinib is also approved for endometrium cancer in combination with pembrolizumab

(*3) NCT04008797

NCT04008797 is an open-label Phase Ib study of E7386 in combination with other anticancer drug, Lenvatinib for the patients with solid tumors. The study has been implemented by Eisai in Japan, Korea, Taiwan, US, and France determine the safety and the recommended phase 2 dose (RP2D) and also to see the pharmacokinetics and efficacy of E7386 + Lenvatinib. Enrolment of each cohort of hepatic, colon, endometrial cancers are ongoing.