On May 23, 2024 Laekna, Inc. (2105.HK), a science-driven, clinical-stage biotechnology company, reported that the company has received approval from the U.S. Food and Drugs Administration for the protocol of the phase III clinical trial of LAE002 (afuresertib, an AKT inhibitor) plus LAE001 (CYP17A1/CYP11B2 dual inhibitor) ("LAE201")in patients with metastatic castration-resistant prostate cancer (mCRPC) following standard of care (SOC) treatment (Press release, Laekna Therapeutics, MAY 23, 2024, https://www.prnewswire.com/news-releases/laekna-announces-fda-approval-for-the-phase-iii-clinical-trial-protocol-of-lae002-afuresertib-plus-lae001-for-the-treatment-of-prostate-cancer-302154036.html [SID1234643647]).

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!

Laekna initiated a Phase II clinical trial of the multi-region clinical trial of the study of LAE201 in the U.S. in June 2021, and South Korea in September 2022. The trial is an open-label, dose-escalation and dose expansion study to assess the efficacy and safety of the combination candidate.

The study demonstrated promising treatment benefit for mCRPC patients. As of Nov 21, 2023, 40 patients who progressed on 1–3 lines of standard treatments, including at least 1 line of abiraterone, or the second generation of AR antagonists, had been enrolled in the recommended phase II dose group. The median rPFS was 8.1 months. This is a significant improvement compared to the median rPFS of 2 to 4 months of mCRPC patients under the standard treatments historically[1]. The combination therapy was generally tolerable with manageable treatment emergent adverse events and recoverable after routine treatments.

"Since the Phase II data of the combination therapy of LAE002 (afuresertib) plus LAE001 demonstrated encouraging anti-tumor activity and safety profile in patients with mCRPC, a following Phase III pivotal trial design has been discussed with the U.S. FDA and the approval for the protocol has been received this month," said Dr. Yong Yue, Chief Medical Officer of Laekna. "The approval marks a significant milestone for Laekna. The mCRPC post 1-3 lines of SOC are difficult-to-treat late stage cancer with poor outcomes. It is an unmet medical need worldwide.We look forward to bringing this precision therapy to mCRPC patients who are in need of novel treatment options."

[1] R. de Wit, et al., 2019;Rhian Sian Davies et al., 2016

About afuresertib

Afuresertib(LAE002) is one of the only two AKT inhibitors in or completed the pivotal-stage clinical development for anti-cancer treatment globally.

Afuresertib is a potent AKT inhibitor that inhibits all three AKT isoforms (AKT1, AKT2 and AKT3). Afuresertib has demonstrated several advantages compared to other AKT inhibitors, including higher efficacy, better potency, more significant tumor inhibition exposure and a better safety profile, based on public data. Capivasertib is the first approved AKT inhibitor from AstraZeneca, which FDA approved for HR+/HER2- breast cancer in November 2023.

With the promising efficacy data from our afuresertib Phase Ib study for HR+/HER2- breast cancer, which was presented in SABCS 2023, Laekna has initiated the Phase III pivotal study. We also continue to develop our clinical trials for the treatment of breast cancer, prostate cancer, ovarian cancer and PD-1/PD-L1 drug-resistant solid tumors to address the unmet medical needs. In several clinical trials, the combination of afuresertib with other therapeutics exhibits favorable efficacy results.

About LAE001

LAE001 is an androgen synthesis inhibitor that inhibits both CYP17A1 and CYP11B2. Laekna in-licensed LAE001 from Novartis in 2017. According to Frost & Sullivan, LAE001 is the only dual CYP17A1/CYP11B2 inhibitor in clinical trials for the treatment of prostate cancer globally.

As a dual CYP17A1/CYP11B2 inhibitor, LAE001 can block both androgen and aldosterone synthesis and potentially be administrated without prednisone, the short-term high dose or long-term exposure of which can lead to a variety of adverse events.

On May 23, 2024 Xspray Pharma AB (publ) (Nasdaq Stockholm: XSPRAY), a Swedish pharmaceutical company which uses its innovative Hynap technology to develop 505(b)(2) improved versions of marketed drugs for the treatment of cancer reported the online publication of its abstract titled "Frequency of Comedication of Proton Pump Inhibitors with Crystalline Dasatinib in Chronic Myeloid Leukemia and Effects on TKI-Bioavailability" for presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on June 3rd, 2024 at 9-12 AM, Poster nr. 120 (1) (Press release, Xspray, MAY 23, 2024, https://www.businesswire.com/news/home/20240523850369/en/Xspray-to-present-data-at-ASCO-highlighting-frequent-comedication-of-PPIs-with-TKIs-in-CML-patients-and-greater-than-expected-negative-effects-on-the-bioavailability-of-crystalline-dasatinib [SID1234643663]).

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!

While Tyrosine Kinase Inhibitors (TKI), including dasatinib, have profoundly improved clinical outcomes in patients with chronic myeloid leukemia (CML), the bioavailability and systematic exposure of the crystalline formulation of dasatinib is reduced by comedication with acid reducing agents which may affect the clinical response and comedication with proton pump inhibitors, such as omeprazole, should be avoided (2).

The collaborative analysis with Uppsala University and the Karolinska Institute and University Hospital demonstrates that 54% of CML patients identified in the Swedish CML-register were prescribed at least one PPI and 34% of TKI-treated patients were comedicated with a PPI. Of those prescribed a PPI, 66% of the prescriptions were by a different healthcare provider. Further, the presentation provides new information on the bioavailability of crystalline dasatinib when comedicated with a PPI, demonstrating a substantially higher than previously reported impact of PPIs on the bioavailability of crystalline dasatinib, with Cmax and AUC24 being reduced by 96% and 88% respectively.

"Consistent absorption and bioavailability of dasatinib are critical for adequate disease control and patient outcomes, this is however often overlooked in clinical practice as our data demonstrates," said Per Andersson, CEO of Xspray. "To address this important issue, we are on track to launch Dasynoc, our optimized version of dasatinib, with a Prescription Act Use Fee Amendment date (PDUFA-date) of 31st of July 2024 and the US commercial launch of Dasynoc on 1st September 2024."

The abstract is now available online at View Source

References:

Dahlén T, Larfors G, Lennernäs H et al. Frequency of Comedication of Proton Pump Inhibitors with Crystalline Dasatinib in Chronic Myeloid Leukemia and Effects on TKI-Bioavailability. American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), Annual Meeting 2024. Chicago. Abstract 6561. Poster 120. View Source
Sprycel (dasatinib) Tablets for oral use. Labeling, Supplement 27. 02 Aug 2023. View Source;ApplNo=021986. Accessed 22 May 2024.

On May 23, 2024 Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS) reported that senior management will present at the upcoming TD Cowen 5th Annual Oncology Innovation Virtual Summit: Insights for ASCO (Free ASCO Whitepaper) & EHA (Free EHA Whitepaper) on Wednesday, May 29, 2024 at 12:00 p.m. Eastern Daylight Time / 9:00 a.m. Pacific Daylight Time (Press release, Coherus Biosciences, MAY 23, 2024, View Source [SID1234643585]). The presentation will be accessible via Webcast through a link on the Investor Events and Presentations section of the Coherus website: View Source This webcast will be available for replay until June 26, 2024.

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 May 23, 2024 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported positive updated results from its Phase 1/2 clinical trial of HB-200 for the treatment of human papillomavirus 16 positive (HPV16+) head and neck cancers (Press release, Hookipa Biotech, MAY 23, 2024, View Source [SID1234643601]). The data were published in the Company’s abstract for the ASCO (Free ASCO Whitepaper) 2024 Annual Meeting and support the Company’s pivotal Phase 2/3 trial design for HB-200 in combination with pembrolizumab in the first line setting.

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 abstract reported data as of January 12, 2024, and included 42 patients treated with HB-200 plus pembrolizumab. The treatment was generally well tolerated with a low rate of treatment-related discontinuation and no treatment-related deaths.

Among a subpopulation of 17 evaluable patients with CPS of 20 or higher, the updated data showed confirmed ORR of 53 percent, CR rate of 18 percent, and DCR of 82 percent. This subpopulation is representative of patients eligible for the Company’s pivotal Phase 2/3 trial, which will begin enrolling patients in the fourth quarter of 2024.

Additional data will be presented in the Head and Neck Oral Abstract Session at the ASCO (Free ASCO Whitepaper) 2024 Annual Meeting on June 4, at 11:09 a.m. CDT. During the presentation, preliminary progression-free survival and overall survival data will be shared for the first time.

"We are happy to provide an update on our clinical data and showcase the meaningful outcomes we are helping to drive for patients," said Joern Aldag, Chief Executive Officer of HOOKIPA. "The data exhibit strong evidence that has helped inform our pivotal Phase 2/3 trial design, which will begin enrolling patients later this year. This update gives us conviction that we are on the right path to achieve our goals and help provide a new targeted therapeutic option for patients battling HPV16+ head and neck cancer."

Results:
HB-200 in combination with pembrolizumab:
The abstract presented data as of January 12, 2024, and included 42 first line patients with HPV16+, PD-L1 positive, recurrent or metastatic head and neck squamous cell carcinoma. The updated data continue to demonstrate a favorable safety profile of HB-200 in combination with pembrolizumab and promising clinical activity as a first line treatment. Median follow-up time was 5.6 months.

HB-200 + pembrolizumab were generally well tolerated. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 6 (14%) patients, serious TRAEs were reported in 3 (7%) patients, and TRAEs leading to treatment discontinuation were reported in 2 (5%) patients. No treatment-related deaths were reported.

Among 35 evaluable patients—those with ≥ 1 post-baseline tumor response assessment—3 confirmed complete responses, 9 confirmed partial responses, and 3 unconfirmed partial responses were observed. Notably, among patients with PD-L1 CPS ≥20 (N=17), ORR, based on confirmed responses, was 53%, CR rate was 18%, and DCR was 82%.

Additional Abstracts at ASCO (Free ASCO Whitepaper) 2024 Annual Meeting:
HB-200 plus chemotherapy (neoadjuvant setting):
In addition, data from an Investigator Initiated Trial (IIT), led by Dr. Ari Rosenberg of the University of Chicago Department of Medicine, will be presented on June 3, in the Head and Neck Rapid Oral Abstract Session. The study concluded that neoadjuvant HB-200 plus chemotherapy for the treatment of patients with non-metastatic HPV16+ oropharyngeal cancers (OPC) is safe and feasible, with early efficacy signal in this setting warranting further study.

Twenty-one patients with HPV16+ OPC were enrolled and treated across multiple cohorts and dose levels. All patients completed neoadjuvant HB-200/chemotherapy and response-stratified locoregional treatment. Deep responses following HB-200/chemotherapy were observed in 17/21 (81%) patients, and in 14/15 (93%) patients treated with higher dose levels 1 or 2. All three patients who underwent transoral robotic surgery (TORS) had no viable tumor at time of surgery. Two patients (9%) had persistent disease following chemoradiotherapy and underwent salvage surgery with no evidence of disease at last follow-up. ctHPV-DNA and HPV16-specific T-cell response data will be presented at the meeting.

Enrollment to the subsequent randomized phase II part is ongoing. Details of the rapid oral presentation are included below.

HB-700 preclinical data:
HB-700 is an investigational arenaviral immunotherapy designed to treat KRAS-mutated lung, colorectal, pancreatic and other cancers. HB-700 is a replicating 2-vector therapy that targets the most common KRAS mutations (G12D, G12V, G12R, G12C and G13D) and has the potential to benefit a broader patient population than single mutation inhibitors.

A transgene cassette consisting of peptide stretches including KRAS mutations G12D, G12V, G12C, G12R and G13D was generated by in silico aided antigen design. KRAS mutation specific CD8+ T cell expansion was evaluated in HLA transgenic mice treated with HB-700 and functionality of induced CD8+ T cells was evaluated by assessing CD8+ T cell mediated killing of mutant KRAS peptide loaded target cells in vivo.

All treatment regimens were well tolerated, and no mortalities or major adverse events were observed. The results indicate efficient induction of KRAS mutation specific T cell responses in HLA transgenic mice. Expanded CD8+ T cells were capable of killing cells loaded with KRAS mutation specific peptides in vivo indicating functionality of the induced T cell responses. No specific cytotoxicity towards target cells pulsed with KRAS wild type peptides was observed in any of the groups. HOOKIPA’s HB-700 investigational product candidate differs from KRAS inhibitors and has a wide range of combinability options including with small-molecule inhibitors. Based on these results, initiation of a Phase I study for the treatment of KRAS mutated cancers is planned.

Abstract details: ASCO (Free ASCO Whitepaper) 2024 Annual Meeting

HB-200:
Title: HB-200 arenavirus-based immunotherapy plus pembrolizumab as first-line treatment of patients with recurrent/metastatic HPV16-positive head and neck cancer: Updated results
Presenter: Dr. Alan L. Ho, Head and Neck Oncologist at Memorial Sloan Kettering Cancer Center and a trial investigator
Abstract Type: Oral abstract
Session Name: Head and Neck Cancer
Session Date and Time: June 4, 2024; 9:45 AM-12:45 PM CDT
Abstract Number: 6005

Investigator Initiated Trial:
Title: Neoadjuvant HPV16-specific arenavirus-based immunotherapy HB-200 plus chemotherapy followed by response-stratified de-intensification in HPV16+ oropharyngeal cancer: TARGET-HPV
Presenter: Dr. Ari Rosenberg, Principal Investigator, TARGET-HPV Trial, University of Chicago Medicine
Abstract Type: Rapid oral abstract
Session Name: Head and Neck Cancer
Session Date and Time: June 3, 2024; 8:00 AM-9:30 AM CDT
Abstract Number: 6017
Trial Sponsor: UChicago Medicine

HB-700
Title: Development of an arenavirus-based immunotherapy for treatment of KRAS mutant cancer
Abstract Type: Abstract only
Session Date: May 23, 2024
Abstract Number: e14672

About HB-200
HB-200 is HOOKIPA’s lead oncology candidate engineered with the company’s proprietary replicating arenaviral vector platform. It comprises two single-vector compounds with arenaviral backbones based on lymphocytic choriomeningitis virus (LCMV) and pichinde virus (PICV). Both express the same transgene encoding an E7E6 fusion protein derived from HPV16. HB-200 is an alternating 2-vector immunotherapy designed to further focus the immune response against the encoded antigen.

HB-200 in combination with pembrolizumab received Fast Track Designation from the U.S. Food and Drug Administration and PRIME designation from the European Medicines Agency for the treatment of first-line HPV16+ recurrent/metastatic oropharyngeal squamous cell carcinoma. These designations are supported by preliminary clinical evidence from the Phase 1/2, open-label, clinical trial (NCT04180215) evaluating safety, T cell response, and efficacy based on objective response rate (ORR) and disease control rate (DCR) as defined by RECIST 1.1. and iRECIST.

About HB-700
HB-700 is an investigational arenaviral immunotherapy designed to treat KRAS-mutated lung, colorectal, pancreatic and other cancers. HB-700 is a replicating 2-vector therapy that targets the most common KRAS mutations (G12D, G12V, G12R, G12C and G13D) and has the potential to benefit a broader patient population than single mutation inhibitors.

On May 23, 2024 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported encouraging clinical data from the dose escalation portion of its Phase 1/2 trial of SNS-101, a conditionally active, human monoclonal antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation) (Press release, Sensei Biotherapeutics, MAY 23, 2024, View Source [SID1234643617]).

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!

"I am pleased that SNS-101 has been well-tolerated in the study, reaching its highest planned dose level with no dose limiting toxicities and demonstrating its potential to successfully overcome the prior challenges of VISTA-targeted programs," said Dr. Shiraj Sen, Medical Oncologist and Director of Clinical Research at NEXT Oncology, Dallas, and a principal investigator for the SNS-101 study. "The data show encouraging signs of clinical activity in a heterogeneous population of patients with advanced solid tumors, where you typically wouldn’t expect to see clinical responses, especially in microsatellite stable colorectal and endometrial tumors. There is a continued unmet need for patient populations that have become resistant or don’t respond to current immunotherapy treatment options. I look forward to continuing to evaluate its progress."

Dose escalation portion of the Phase 1/2 clinical trial

The dose escalation portion of the Phase 1/2 clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101. This study assesses SNS-101 both as monotherapy and in combination with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab, 350 mg), in patients with advanced solid tumors with primary (unfavorable candidates for immunotherapy) or acquired PD-1 therapy resistance (progressed on prior anti-PD-1 therapy).

A total of 34 patients received SNS-101 once every 3 weeks, with 16 patients in the monotherapy arm and 18 patients in the combination arm. The majority of patients (85%) had a tumor type that is typically unresponsive to PD-1 monotherapy ("cold" tumors).

As of the April 30, 2024 data cutoff, SNS-101 demonstrated preliminary evidence of promising clinical activity in multiple tumor types, including:

One microsatellite stable (MSS) endometrial cancer patient that received SNS-101 plus cemiplimab had a confirmed partial response (59% decrease) and remains on study at 30+ weeks. MSS endometrial cancer has been previously shown to have a low response rate to monotherapy immunotherapy treatments.
One MSS colorectal cancer (CRC) patient that received SNS-101 plus cemiplimab remained on study for 18 weeks and had tumor regression of 27%. MSS CRC has been previously shown to be unresponsive to PD-1 treatments.
One pembrolizumab-resistant renal cell carcinoma patient that received SNS-101 plus cemiplimab remained on study for 12 weeks and had tumor regression of 18%.
One pembrolizumab-resistant human papillomavirus (HPV)+ head and neck cancer patient that received SNS-101 as monotherapy remained on study for 12 weeks and had tumor regression of 17%.
These clinical data are consistent with preclinical studies suggesting therapeutically relevant clinical doses of SNS-101 at 3mg/kg or higher. Additionally, preliminary flow-based pharmacodynamic analysis showed dose-dependent changes in specific T-cell populations suggesting SNS-101 may be having a pharmacological effect on T-cell subsets.

SNS-101 demonstrated a potentially best-in-class pharmacokinetic (PK) profile with linear elimination kinetics and dose-proportional increases in exposure, supporting once every three week dosing. The data are consistent with lack of target-mediated drug disposition (TMDD), which has been observed in non-conditionally active anti-VISTA antibodies.

SNS-101 was well tolerated alone and in combination with cemiplimab, with no dose-limiting toxicities observed. The majority of AEs were Grade 1 or 2 in severity. Two patients experienced Grade 1 cytokine release syndrome (CRS), one in monotherapy and one in combination, both at the highest dose of SNS-101. Both cases were mild and manageable, demonstrating that SNS-101 has the potential to overcome a key hurdle that hindered first-generation VISTA-targeting approaches. Four patients in the combination cohort experienced immune-mediated events. There were also no significant changes to key inflammatory cytokine levels, including interferon gamma, interleukin-6, interleukin-10, interleukin-8, TNF-alpha, and CCL5-RANTES, across cohorts.

"The dose escalation portion of the Phase 1/2 trial of SNS-101 answers the critical question of whether a pH-selective approach can overcome the previous hurdles associated with targeting VISTA, which included severe safety and PK issues. We believe the topline data presented today marks an important milestone and validates the mechanism of action by demonstrating the potentially best-in-class PK and a well-tolerated safety profile of SNS-101 at therapeutically relevant dose levels," said Ron Weitzman, Chief Medical Officer of Sensei Bio. "We saw promising clinical activity primarily in tumor types that don’t typically respond to PD-1 monotherapy and look forward to progressing through the expansion phase of the study."

Ongoing dose expansion portion of the Phase 1/2 clinical trial

Patient enrollment is advancing in the dose expansion portion of the Phase 1/2 study. The Company expects to report initial data from the dose expansion cohorts and to hold an end-of-Phase 1 meeting with the FDA by the end of 2024.

ASCO presentation

The data will be presented in a poster presentation entitled "Initial results from a first-in-human phase 1 study of SNS-101 (pH-selective anti-VISTA antibody) alone or in combination with cemiplimab in patients with advanced solid tumors," on June 1, 2024, at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago, IL. The poster will be available on the Sensei website at the start of the poster presentation.

Investor webcast

Sensei will host a webcast on Monday, June 3, 2024, at 8:00 a.m. ET (7:00 a.m. CT) to discuss the data. Participating alongside Company management will be Dr. Shiraj Sen, M.D., Ph.D., Medical Oncologist and Director of Clinical Research at NEXT Oncology-Dallas. Dr. Sen is an investigator on the ongoing Phase 1/2 clinical trial for SNS-101, and lead author of the SNS-101 poster. The live event can be accessed here: View Source and can be accessed on the Investor page of Sensei’s website at View Source A replay of the webcast will be available after the completion of the event.