On July 10, 2024 Kazia Therapeutics Limited (NASDAQ: KZIA), an oncology-focused drug development company, reported results from GBM-AGILE, a phase II/III study that included an evaluation of paxalisib versus standard of care (SOC) for patients with glioblastoma (NCT03522298), a life-threatening brain cancer, where there is an urgent unmet need for new therapeutics (Press release, Kazia Therapeutics, JUL 10, 2024, View Source [SID1234644771]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

GBM AGILE STUDY

GBM AGILE is an adaptive phase II/III global trial sponsored by the Global Coalition for Adaptive Research (GCAR), a nonprofit organization comprised of some of the world’s foremost clinical, translational, and basic science researchers, from institutions such as Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute. The trial is designed to efficiently screen for and characterize the response of glioblastoma (GBM) patients to novel investigative agents. Utilizing a complex innovative design, Bayesian principles are applied to the primary endpoint (Overall Survival) comparison of the investigational agents to patients receiving Standard of Care (SOC) enrolled from the study start (also referred to as cumulative control population). In general, secondary analyses and endpoints are assessed based on established statistical models in comparison to the control patients enrolled at the same time as the investigational agent (concurrent control population).

Paxalisib is the third drug candidate to complete its evaluation in the study and was evaluated in newly diagnosed glioblastoma patients with unmethylated MGMT promoter status as well as in patients with recurrent disease.

GBM AGILE Paxalisib Results

Kazia CEO, Dr John Friend stated, "We are excited to have shown a 3.8 month improvement in overall survival, an approximate 33% improvement, for newly diagnosed unmethylated patients with GBM compared to the concurrent standard of care arm. Having comparable Overall Survival data across two independent studies is a compelling outcome in this difficult to treat glioblastoma population. We look forward to discussing possible approaches for an accelerated approval pathway for paxalisib with the FDA."

A total of 313 newly diagnosed unmethylated (NDU) patients and recurrent patients being treated at top US cancer hospitals were randomized in Stage 1 to either a paxalisib treatment arm (60 mg/day) or the SOC concurrent control arm from January 2021 to May 2022. The cumulative control arm was enrolled from July 2019 (GBM Agile study start date) to May 2022.

For the primary analysis the median Overall Survival (OS) was 14.77 months for paxalisib-treated NDU patients (n=54) versus 13.84 months for cumulative SOC NDU patients (n=75).

For a prespecified secondary analysis in the NDU patients, median OS was 15.54 months in the paxalisib arm (n=54) versus 11.89 months for concurrent SOC (n=46). In addition, a prespecified sensitivity analysis in NDU patients showed similar median OS difference between paxalisib treated patients (15.54 months) and concurrent SOC patients (11.70 months).

The secondary analysis results are consistent with the previously reported Company-sponsored phase II study, where median OS was 15.7 months (n=27) for paxalisib treated NDU patients compared to 12.7 months historically reported with temozolomide in this patient group (Wen 2022).

Paxalisib was well tolerated in GBM-AGILE, and no new safety signals were identified in this patient population.

An efficacy signal was not detected in the recurrent disease population (median OS of 9.69 months for concurrent SOC (n=113) versus 8.05 months for paxalisib (n=100). Similar results in this population have been reported in the other two drug candidates that have completed the GBM AGILE trial. Kazia is currently pursuing further analyses of this data to elucidate potential signals for further consideration.

Based on the totality of data available from all completed paxalisib clinical studies in newly diagnosed unmethylated GBM patients, Kazia will request a meeting with the US Food & Drug Administration (FDA) to discuss the results and determine if a potential path to accelerated approval is appropriate for paxalisib.

Paxalisib has previously received orphan drug designation and fast track designation from the FDA for glioblastoma in unmethylated MGMT promoter status patients, following radiation plus temozolomide therapy.

Full data including secondary endpoints from the paxalisib arm of the GBM AGILE study is expected to be presented at a scientific meeting later this year.

On July 10, 2024 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company that aims to develop the world’s most potent vaccines, reported that the Compensation Committee of the company’s Board of Directors granted one employee nonqualified stock options to purchase an aggregate of 39,000 shares of its common stock with an exercise price of $0.57, which is equal to the closing price of Gritstone’s common stock on July 3, 2024, the date of the grant (Press release, Gritstone Bio, JUL 10, 2024, View Source [SID1234644770]). These stock options are part of an inducement material to the new employees becoming an employee of Gritstone, in accordance with Nasdaq Listing Rule 5635(c)(4).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The stock options will vest over a four-year period, with 25% of the options vesting on the first anniversary of the employees’ date of hire, and 1/48th of the options vesting monthly thereafter, subject to the employees’ continued employment with Gritstone on such vesting dates. The stock options are subject to the terms and conditions of Gritstone’s 2021 Employment Inducement Incentive Award Plan and the stock option agreement covering the grant.

On July 10, 2024 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of emavusertib (CA-4948), an orally available, small molecule IRAK4 inhibitor, reported that James Dentzer, President and Chief Executive Officer of Curis, will present at the Jones Healthcare Seaside Summit 2024 on July 15, 2024 at 8:00 a.m. PT (11:00 a.m. ET) (Press release, Curis, JUL 10, 2024, View Source [SID1234644768]). A live webcast and archived replay will be available and can be accessed here or on the Events & Presentations section of Curis’s website.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On July 10, 2024 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported an update on the on-going OPTIMIZE-1 clinical Phase 2 trial with the company’s lead asset, mitazalimab (Press release, Alligator Bioscience, JUL 10, 2024, View Source [SID1234644766]). All patients in the 450 µg/kg back-fill cohort have been enrolled.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The additional cohort was enrolled in order to provide further dose characterization following advice from the FDA, to ensure mitazalimab Phase 3 readiness.

"We are pleased to see the recruitment completed in a very swift manner, a testament to the committed work by the Alligator team and the great engagement of the study investigators and their research staff involved in the OPTIMIZE-1 trial", said Søren Bregenholt, CEO of Alligator Bioscience. "We are committed to bringing mitazalimab to patients as soon as possible, and this back-fill cohort is an important step to complete the dose-characterization and ensure mitazalimab’s Phase 3-readiness in accordance with the guidance from FDA."
OPTIMIZE-1, an open-label, single-arm, multicenter, Phase 1b/2 study, assessed the safety and efficacy of mitazalimab (CD40 mAb agonist) in combination with standard of care chemotherapy mFOLFIRINOX in 1st line pancreatic cancer. On June 26, the 18-month follow-up analysis was reported, demonstrating robust data with substantial survival benefits compared to standard of care chemotherapy.

About pancreatic cancer

Pancreatic cancer is the 12th largest cancer by number of patients. It is expected to become the second leading cause of cancer death in the western world by 2030. There are about 200,000 annual cases in the U.S. and the EU, with very poor prognosis: five-year survival is about 10% and median survival about 6 months. For 80% of patients, the only option is chemotherapy that offers only marginal benefit. FOLFIRINOX is expected to be the preferred first line regimen in the U.S. and the EU for patients with good performance status.

On July 10, 2024 Imugene Limited (ASX:IMU), a clinical stage immune-oncology company, reported that the first patient has been dosed in its trial for bile tract cancer (cholangiocarcinoma) patients (Press release, Imugene, JUL 10, 2024, View Source [SID1234644754]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This is an expansion of the MAST (Metastatic Advanced Solid Tumours) Phase 1 trial after early responses were observed in gastrointestinal cancers, and particularly cholangiocarcinoma, using Imugene’s cancer-killing virus CF33 (VAXINIA).

The first patient in the trial was treated at St. Vincent’s Hospital, with a total of 10 patients to be enrolled.

Imugene Managing Director & CEO Leslie Chong said: "Given the results we’ve seen to date we are eager to see the potential of VAXINIA in bile tract cancer. We look forward to now advancing to the higher doses in the trial to gather further key data and make a genuine difference to patients in need of innovative treatment options."

In November 2023, the FDA granted the VAXINIA MAST clinical program Fast Track Designation for the treatment of bile tract cancer, which allows Imugene closer cooperation with the FDA to expedite the program and potential approval process.

Bile tract cancer is a rare disease in which malignant cancer cells form in the bile ducts. It is difficult to treat and generally responds poorly to immunotherapy drugs.

One patient with bile tract cancer who had failed three prior lines of therapy received a mid-dose of IT-administered monotherapy VAXINIA achieved a complete response, meaning the disappearance of all signs of cancer in response to treatment, and the patient has been on the study for over 620 days. A second patient with cholangiocarcinoma, who has also progressed on prior drug therapies, achieved stable disease for more than four months upon receiving IV-administered VAXINIA.

The Cohort Review Committee has now cleared the fifth cohort for both arms, intratumoral (IT) and intravenous (IV), of the monotherapy dose escalation portion of the MAST trial, with no safety signals observed thus far. Consequently, the sixth cohort of each arm of the dose escalation trial are now open and enrolling.

*Further dose escalation to continue as long as no safety issues are observed

The multicenter, Phase 1, MAST trial commenced by delivering a low dose of VAXINIA to patients with metastatic or advanced solid tumours who have had at least two prior lines of standard of care treatment. With no safety signals identified to date, the trial has since progressed through the monotherapy dose escalation cohorts as well as the combination study, whereby VAXINIA is administered with well-known checkpoint inhibitor pembrolizumab. CF33 oncolytic virus, developed by City of Hope, has been shown to shrink colon, lung, breast, ovarian and pancreatic cancer tumours in preclinical laboratory and animal models¹.