On September 10, 2022 Cardiff Oncology, Inc. ( Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported new preclinical and clinical data from its program in KRAS-mutated mCRC (Press release, Cardiff Oncology, SEP 10, 2022, View Source [SID1234619372]). The data are featured in two posters being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022, which is taking place at the Paris Expo Porte de Versailles in Paris, France, and virtually.

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Poster 397P: Early Decreases in KRAS Mutant Allele Frequency (MAF) Predict Clinical Benefit to the PLK1 Inhibitor Onvansertib in Combination with FOLFIRI/bev in 2L Treatment of Metastatic Colorectal Carcinoma (mCRC)

Poster 397P includes updated data (data cut-off date: July 25, 2022), as well as the results of correlative biomarker analyses from a Phase 1b/2 clinical trial of onvansertib plus FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC. Measures of clinical response were compared between subsets of patients defined as KRAS responders or non-responders. KRAS responders were defined as patients with a ≥90% decrease in KRAS mutant allele frequency (MAF) in circulating tumor DNA (ctDNA) after one treatment cycle.

"The data from this trial show onvansertib plus FOLFIRI and bevacizumab outperforming historical controls on multiple key endpoints and are highly encouraging," said Heinz-Josef Lenz, MD, FACP, professor of medicine at USC Norris Comprehensive Cancer Center and the trial’s principal investigator. "They suggest trial participants with various KRAS mutations experience durable clinical benefits and that the onvansertib-FOLFIRI combination is avoiding the mechanisms that typically drive rapid acquired resistance to the standard-of-care (SoC). This highlights onvansertib’s potential to fill a crucial gap in mCRC’s therapeutic paradigm, as there are currently limited options available for second line patients. In addition, the significant increases between response rates and progression-free survival in KRAS responders point to changes in MAF as a potential blood-based biomarker that could aid in treatment decisions."

Key data and conclusions presented in the poster include:

Overall response rate (ORR) and median progression-free survival (mPFS) reported in Phase 1b/2 trial substantially exceed those reported in historical control trials

ORR across all evaluable patients was 35%, with 17 of 48 evaluable patients achieving an objective response and responses have been observed across multiple KRAS variants
Median duration of response (mDoR) across all evaluable patients was 11.7 months (95% confidence interval (CI): 8.9 – not reached)
mPFS across all evaluable patients was 9.3 months (95% CI: 7.6 – 13.5)
Historical control trials of different drug combinations, including the standard-of-care (SOC) of FOLFIRI with bevacizumab, in similar patient populations have shown ORR and mPFS of 5 – 13% and ~4.5 – 5.7 months, respectively1-4
KRAS responders showed significantly greater ORR and mPFS compared to non-responders

ORR in KRAS responders vs. KRAS non-responders: 63.6% (14/22) vs. 8.7% (2/23) (p = 0.00014)
mPFS in KRAS responders vs. KRAS non-responders: 12.6 months vs. 6.0 months (p=0.019)
Poster 366P: The PLK1 Inhibitor Onvansertib Overcomes Irinotecan Resistance in RAS-mutated Metastatic Colorectal Cancer (mCRC) In Vivo and in Patients

Poster 366P includes findings (as of August 5, 2022) from Cardiff Oncology’s EAP of onvansertib in KRAS-mutated mCRC, as well as data from murine studies evaluating onvansertib in combination with irinotecan in 6 PDX models of irinotecan-resistant, RAS-mutated CRC. Clinical findings reported in the Expanded Access Program (EAP) were compared between KRAS responders and non-responders. To enroll in the EAP, a patient must have been ineligible for the Phase 1b/2 clinical trial having received prior treatment with irinotecan or failed or progressed on multiple prior lines of standard-of-care therapy. EAP patients are treated with the same treatment regimen (onvansertib 15 mg/m2 plus FOLFIRI and bevacizumab) and dosing schedule as patients in the Phase 1b/2 clinical trial.

Scott Kopetz, MD, PhD, FACP, professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center commented, "Currently available third-line or later treatment options for patients are severely limited, due in large part to the high prevalence of tumors that show resistance to irinotecan. Based on the findings being presented at ESMO (Free ESMO Whitepaper), combining onvansertib with the current SOC appears to be an innovative strategy that can overcome irinotecan resistance and address a broad and pressing unmet need. This hypothesis is further supported by onvansertib’s mechanism of action, which targets DNA damage repair pathways underlying resistance to irinotecan and other chemotherapeutic agents."

Key findings and conclusions presented in the poster include:

EAP patients with prior irinotecan treatment (43 out of a total of 51 EAP patients) showed clinical benefit following treatment with onvansertib plus FOLFIRI/bevacizumab

mPFS was 4.04 months (95% CI: 2.96 – 8.38); 6-month PFS rate was 37.3% (95% CI: 24.9 – 55.8)
Of EAP patients with prior irinotecan treatment, KRAS responders had significantly longer PFS compared to non-responders.

mPFS in KRAS responders vs. KRAS non-responders: 11.18 months vs. 3.25 months (p=0.0014)
The combination of onvansertib and irinotecan showed significantly greater anti-tumor activity compared to onvansertib monotherapy in 5 of 6 tested PDX models of irinotecan-resistant, RAS-mutated CRC.

The ESMO (Free ESMO Whitepaper) posters are currently available for viewing on the congress’s virtual platform and will also be presented by Drs. Lenz and Kopetz during Poster Sessions 8 and 7, respectively, on September 11, 2022. Following the congress, the posters will be available on the "Scientific Presentations" section of the Cardiff Oncology website at View Source

Clinical and Corporate Update Conference Call and Webcast
Cardiff Oncology will host a webcast and conference call to provide a clinical and corporate update to the investment community on Monday, September 12, 2022 at 4:30 PM ET. The event will feature discussions on the planned development pathway for onvansertib in KRAS-mutated metastatic colorectal cancer and updates on other development programs. In addition, company management will provide data updates from ongoing clinical trials. To access the call, please dial 1-877-407-9208 (domestic) or 1-201-493-6784 (international) and refer to conference ID 13731618. The conference call will also be webcast live and a link to the webcast can be accessed here. A replay of the webcast will be available by visiting the "Events" section of the Cardiff Oncology website after its conclusion.

About the Phase 1b/2 Trial of Onvansertib in the Second-Line Treatment of KRAS-mutated mCRC
This is a multi-center, single-arm, Phase 1b/2 trial of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab) to evaluate the safety and preliminary efficacy of the combination regimen in the second-line treatment of patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second–Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, is enrolling patients with histologically confirmed metastatic and unresectable colorectal carcinoma harboring a KRAS mutation. Patients must also have experienced disease progression or treatment intolerance to first-line treatment with fluoropyrimidine and oxaliplatin (FOLFOX or CapeOx) with or without bevacizumab to be eligible. The trial is being conducted at the following cancer centers across the U.S.: USC Norris Comprehensive Cancer Center, The Mayo Clinic (Arizona, Rochester, and Jacksonville), Kansas University Medical Center (KUMC), CARTI Cancer Center and Inova Schar Cancer Institute. For more information on the trial, please visit NCT03829410.

About the EAP for Onvansertib in KRAS-mutated mCRC
Sometimes called "compassionate use", expanded access is a potential pathway for a patient with a serious or life-threatening disease to gain access to an investigational drug for treatment outside of a clinical trial, particularly when no comparable or satisfactory alternative therapy options are available. The Cardiff Oncology EAP in KRAS-mutated mCRC is using the same combination treatment regimen (onvansertib 15 mg/m2 + FOLFIRI and bevacizumab) and dosing schedule as the ongoing Phase 1b/2 clinical trial and is intended for patients that have progressed on prior therapy and do not meet the second line eligibility criteria for enrollment in the clinical trial. The program has reached capacity and is no longer open to enrollment.

On September 10, 2022 POINT Biopharma Global Inc. (NASDAQ: PNT) (the "Company" or "POINT"), a company accelerating the discovery, development and global access to life-changing radiopharmaceuticals, reported a poster at ESMO (Free ESMO Whitepaper) Congress 2022 containing updated efficacy and safety data from the 27-patient safety and dosimetry lead-in cohort for the Company’s phase 3 SPLASH trial (NCT04647526) evaluating PNT2002 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) (Press release, Point Biopharma, SEP 10, 2022, View Source [SID1234619371]). Key findings include a median rPFS time of 11.5 months, along with a well-tolerated safety profile with no treatment-related deaths and few treatment-related AEs of grade 3 or higher.

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"rPFS is the primary endpoint of the SPLASH trial, making these positive signals from the lead-in cohort extremely promising," said Dr. Neil Fleshner, Chief Medical Officer of POINT Biopharma. "I believe the dosing schedule of four cycles of 177Lu-PNT2002 at 6.8 GBq per cycle every 8 weeks is a unique differentiator offering lower overall whole-body radiation and shorter overall treatment than currently approved PSMA RLT therapies."

The full poster is available to download at the Company’s investor relations website, located at View Source Upcoming third-party coverage of the data will include video interviews of Dr. Fleshner by UroToday, and of Dr. Aaron R. Hansen by VuMedi. Dr. Hansen is Deputy Director for the Division of Cancer Services at Metro South Health, a Medical Oncologist at Princess Alexandra Hospital, and an Associate Professor of Medicine at the University of Toronto and the University of Queensland.

The phase 3 SPLASH trial is a multi-center, randomized, open label assessment of PNT2002 in participants with prostate-specific membrane antigen (PSMA)-expressing mCRPC who have progressed on androgen receptor pathway inhibitor (ARPI) therapy. Compared to other currently approved radioligand therapies for prostate cancer, SPLASH is evaluating PNT2002 earlier in the treatment pathway and using fewer and lower doses. The treatment regimen for the lead-in cohort is the same as the regimen being investigated in the randomization part of the trial: participants receive up to four cycles of 177Lu-PNT2002 at 6.8 GBq per cycle every 8 weeks. The SPLASH trial is currently enrolling patients across 53 sites in North America, Europe, and UK, and site activations remain ongoing to expedite accrual.

The poster is titled "Efficacy and Safety of 177Lu-PNT2002 prostate-specific membrane antigen (PSMA) Therapy in Metastatic Castration Resistant Prostate Cancer (mCRPC): Initial Results from SPLASH" (e-Poster #1400P). The poster’s newly released data were based on a median follow-up of 11.7 months, updating the previously published abstract which was based on a median follow-up of 7.6 months. Key findings for the lead-in cohort include:

Median rPFS was 11.5 months, as compared to the control arm benchmarks of 3.5–4.2 months for individuals with progressive mCRPC post-ARPI failure receiving similar treatment1,2
Median overall survival had not been reached with an 11.7-month median duration of follow-up from time of enrollment
A radiographic objective response was achieved in 60% of the 10 participants with evaluable disease at baseline
84.8% of individuals imaged met PSMA eligibility criteria
From a median baseline PSA (ng/mL) of 22 (range 0.3–701.0), 11 (42%) participants achieved a PSA50 response
PNT2002 was well tolerated with no treatment-related deaths and few treatment-related AEs of grade 3 or higher
Treatment-related adverse events occurring in >10% of participants included dry mouth (25.9% of participants; all grade 1), fatigue (22.2%; grades 1-2), nausea (18.5%; grades 1-2), and anaemia (14.8%; grades 1-3)
"In this patient population, which was not as heavily pre-treated as the population studied in the published randomized trials of 177Lu-PSMA-617, PNT2002 was very well tolerated," said Scott Tagawa, MD, MS, FACP, Medical Oncologist at Weill Cornell Medicine, Professor of Medicine at Meyer Cancer Center, SPLASH trial investigator, and senior author on the SPLASH poster at ESMO (Free ESMO Whitepaper). "The early efficacy signals of PSA and measurable disease responses, combined with the favorable, though non-randomized, rPFS data, are encouraging for success of the phase 3 study."

Prior to the publication of the lead-in cohort data, the Company hosted a 45-minute educational webinar on August 18, 2022 entitled "Understanding the PNT2002 SPLASH Trial Control Arm" featuring presentations from Dr. Oliver Sartor and Dr. Kim Chi.

Both the poster and the webinar are available under the Presentations tab of the Investors section of the Company’s website, located at View Source

1. de Bono J, Mateo J, Fizazi K, et al. N Engl J Med 2020;382:2091–102.
2. Powles T, Yuen KC, Gillessen S, et al. Nature 2022;28:144–53.

Potential conflict of interest disclosure: Dr. Tagawa has received research funding and honoraria for consulting from POINT.

About the SPLASH Trial
The phase 3 SPLASH trial is a multi-center, randomized, open label assessment of PNT2002 in participants with PSMA-expressing mCRPC who have progressed on androgen receptor pathway inhibitor (ARPI) therapy and refuse, or are not eligible for, chemotherapy. The randomization phase of the study is expected to enroll approximately 400 participants across North America, Europe, and the United Kingdom. Participants will be randomized 2:1 with participants in arm A receiving PNT2002 and participants in arm B receiving either abiraterone or enzalutamide. Participants in arm B who experience centrally assessed radiographic progression and meet protocol eligibility will have the option to crossover and receive PNT2002. Patients will be subject to follow-up for up to 5 years from their first PNT2002 dose. The primary endpoint of the study is radiographic progression-free survival. Key secondary endpoints include overall response rate, overall survival, and pharmacokinetics.

On September 10, 2022 Bicara Therapeutics, a clinical-stage biotechnology company developing dual-action biologics designed to modulate the tumor microenvironment to elicit a potent and durable anti-tumor response, reported that new clinical data from the ongoing Phase 1/1b trial of BCA101, an EGFR / TGF-b bifunctional antibody, as a monotherapy and in combination with pembrolizumab (Press release, Bicara Therapeutics, SEP 10, 2022, View Source;utm_medium=rss&utm_campaign=bicara-therapeutics-presents-new-data-from-ongoing-phase-1-1b-trial-of-lead-first-in-class-bifunctional-program-bca101-at-the-european-society-for-medical-oncology-esmo-congress-2022 [SID1234619363]). These data were presented in an oral presentation session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022, being held in Paris, France.

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"Seeing durable responses in our patients with head and neck cancer at this early stage of clinical development is very encouraging," said Glenn J. Hanna, M.D., Director of the Center for Salivary and Rare Head and Neck Cancers, Dana-Farber Cancer Institute, and Principal Investigator for the Phase 1/1b clinical trial of BCA101. "BCA101, a first-in-class molecule, may represent a potential new option for our patients. We look forward to continuing enrollment in the dose expansion portion of the study."

"The data presented today underline the significant progress we have made in the last few months to demonstrate the efficacy of BCA101," said Liviu Niculescu, M.D., Chief Medical Officer of Bicara Therapeutics. "We are extremely encouraged by the durable responses we are seeing in heavily pre-treated patients, and by the responses we are seeing in combination with pembrolizumab in a front-line head and neck patient population, enabling us to achieve the first efficacy threshold in dose expansion."

BCA101 Data Highlights:

In the first-line recurrent/metastatic HNSCC dose expansion combination cohort, the four partial responses needed to open Stage 2 have been observed prior to completing Stage 1 enrollment.
BCA101 is well tolerated and clinically active as a single agent and in combination with pembrolizumab in patients with head and neck squamous cell carcinoma (HNSCC), squamous cell carcinoma of the anal canal (SCAC) and squamous non-small cell lung cancer (SqNSCLC).
In dose escalation, single-agent activity, including one durable partial response, was observed among late-line patients treated with BCA101. A disease control rate of 58% was observed in evaluable patients at doses above 1000 mg.
In the combination dose escalation arm, a partial response was observed in four out of 13 (31%) evaluable patients (two each in SCAC and HNSCC) as well as a disease control rate of 69%. Patients had a median of four prior lines of therapy prior to entering the BCA101 study.
All four patients with responses have been on study for more than eight months, including one HNSCC patient who was refractory to anti-PD-1 therapy and cetuximab.
BCA101 is currently being evaluated in a Phase 1/1b study as monotherapy and in combination with pembrolizumab as a first-line therapy in patients with unresectable, recurrent or metastatic HNSCC and as second-line therapy in patients with advanced SCAC who have received prior chemotherapy. A third cohort of patients with advanced or incurable cutaneous squamous cell carcinoma who have received previous anti-PD-1 therapy will be treated with BCA101 as monotherapy. Bicara initiated the dose expansion arm of this study in February 2022.

Webcast Details:

Date and time: Monday, September 12, 2022 at 10:30 a.m. ET
To register: Please visit the Online Experiences website to register for the live event. Following the live webcast, an archived replay will be available on the Bicara website.
About BCA101

BCA101 is a first-in-class EGFR / TGF-β-trap bifunctional antibody designed to enhance both innate and adaptive immune responses directly at the site of the tumor by binding to the well-validated EGFR antigen and disabling TGF-β, a signaling molecule that plays a key role in suppressing the immune response in the tumor microenvironment. Promising preclinical data suggest that BCA101 is superior to the anti-EGFR antibody cetuximab in preventing tumor recurrence, as well as in restoring immune activation. An ongoing Phase 1/1b dose-escalation clinical trial of BCA101 is currently enrolling in front-line HNSCC and additional solid tumors. For more information, please visit study number NCT04429542 at www.clinicaltrials.gov.

On September 10, 2022 Wugen, Inc., a clinical-stage biotechnology company developing a pipeline of off-the-shelf cell therapies to treat a broad range of hematological and solid tumor malignancies, reported that preclinical data on WU-NK-101, the company’s lead memory natural killer (NK) cell therapy product, in a poster session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022, taking place in Paris, France from September 9-13, 2022 (Press release, Wugen, SEP 10, 2022, View Source [SID1234619362]).

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"We are pleased to present these data and build on the growing body of evidence validating our best-in-class memory NK cell platform," said Dan Kemp, Ph.D., President and Chief Executive Officer of Wugen. "Today’s findings are an important step forward as we continue to advance WU-NK-101 into clinical development for both solid tumors and acute myeloid leukemia (AML)."

"While adoptive cell therapies have proven a powerful tool against hematological cancers, their application to solid tumors has historically been limited by restricted cell trafficking to tumors and the harsh tumor microenvironment (TME)," added Sergio Rutella, M.D., Ph.D., FRCPath, FRSB, Professor of Cancer Immunotherapy at Nottingham Trent University and presenting author. "These findings are highly promising and suggest that memory NK cells can circumvent these challenges, with broad potential therapeutic applications for solid tumors."

Today’s presentation highlighted the following:

WU-NK-101 exhibited enhanced metabolic fitness and metabolic flexibility, contributing to resilient and enhanced function within the adverse immunosuppressive TME relative to conventional NK (cNK) cells.
WU-NK-101 showed potent cytotoxicity against tumor cells. In vitro, WU-NK-101 in combination with monoclonal antibodies (mAbs) demonstrated a statistically significant increase in antibody-dependent cellular cytotoxicity (ADCC) activity when compared to mAbs alone, which was further validated by significant anti-tumor activity in vivo when compared to WU-NK-101 alone.
WU-NK-101 in combination with mAbs demonstrated robust anti-tumor activity, showing enhanced trafficking, tumor infiltration, and persistence.
These data suggest that WU-NK-101 may overcome the current limitations of adoptive cellular therapies and support its clinical development in the solid tumor setting.
The details of Wugen’s presentation at ESMO (Free ESMO Whitepaper) are as follows:

Title: WU-NK-101: An Enhanced NK Cell Therapy Optimized for Function in the Tumor Microenvironment (TME)

Abstract Number: 11P

Date and Time: Sunday, September 11, 2022, from 12:00 – 13:00 CEST (6:00 – 7:00 a.m. EDT)

Location: Paris Expo Porte De Versailles, Poster Area, Hall 4

Additional meeting information can be found at View Source

About WU-NK-101

WU-NK-101 is a novel immunotherapy harnessing the power of memory natural killer (NK) cells to treat liquid and solid tumors. Memory NK cells are hyper-functional, long-lasting immune cells that exhibit enhanced anti-tumor activity and a cytokine-induced memory-like (CIML) phenotype. This rare cell population has a superior phenotype, proliferation capacity, and metabolic fitness that makes it better suited for cancer therapy than other NK cell therapies. Wugen is applying its proprietary MonetaTM platform to advance WU-NK-101 as a commercially scalable, off-the-shelf cell therapy for cancer. WU-NK-101 is currently in development for acute myelogenous leukemia (AML) and solid tumors.

On September 10, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, reported that updates from its solid tumor development program for cornerstone PD-1 antibody tislelizumab at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 in Paris (Press release, BeiGene, SEP 10, 2022, View Source [SID1234619361]).

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Results from the Phase 3 RATIONALE 301 trial of tislelizumab versus sorafenib as first-line treatment in patients with unresectable hepatocellular carcinoma were accepted as a late-breaking abstract (LBA36) and presented at an oral session on Saturday, September 10. In the final analysis of 674 patients enrolled from Asia, Europe, and U.S., RATIONALE 301 met its primary endpoint of overall survival (OS) non-inferiority, with a median OS of 15.9 months for tislelizumab compared with an OS of 14.1 months for sorafenib (HR: 0.85 [95.003% CI: 0.712, 1.019]); superiority was subsequently tested, which was not met. OS data were consistent across all pre-specified subgroups, including regions.

In the RATIONALE 301 trial, tislelizumab was associated with a higher objective response rate (ORR) (14.3% vs. 5.4%) and more durable responses (median duration of response (DoR) 36.1 months vs. 11.0 months) compared with sorafenib. Median progression-free survival (PFS) for tislelizumab versus sorafenib was 2.1 months vs. 3.4 months respectively; HR: 1.11 [95% CI: 0.92, 1.33].

The safety profiles for tislelizumab and sorafenib treatments were consistent with previous studies, and tislelizumab demonstrated a comparatively favorable profile versus sorafenib with lower incidence rates of grade >3 adverse events (AEs) and AEs leading to discontinuation (48.2% vs 65.4% and 10.9% vs 18.5% respectively). AEs leading to death were low across both tislelizumab (4.4%) and sorafenib (5.2%) arm.

"The RATIONALE 301 study results confirm a durable overall survival benefit of single agent tislelizumab and we are pleased that the safety profile for tislelizumab is consistent with previous studies. While targeted therapies can be an important treatment modality for advanced hepatocellular cancer, the safety and tolerability profile remain an important consideration," said Mark Lanasa, M.D., Ph.D, Chief Medical Officer, Solid Tumors, at BeiGene. "We’re pleased to share the data at ESMO (Free ESMO Whitepaper) today and to engage with leading oncology researchers about our expansive clinical development program for tislelizumab in solid tumors."

In addition to the late-breaking Phase 3 RATIONALE 301 results, BeiGene shared posters demonstrating a consistent response for tislelizumab across pre-specified subgroups in a Phase 3 trial and indications of anti-tumor activity and tolerable safety profile in a Phase 1 trial with tislelizumab in combination with chemotherapy and investigational anti-TIGIT antibody ociperlimab:

Abstract 1031P – RATIONALE 303 (NCT03358875): Tislelizumab demonstrated favorable OS, PFS, DoR, and ORR compared with docetaxel, regardless of subgroup, in a prespecified analysis of Asian versus non-Asian patients in the global RATIONALE 303 study of tislelizumab versus docetaxel as second- or third-line therapy in previously treated patients with locally advanced non-small cell lung cancer (NSCLC) Lower rates of treatment-emergent adverse events were reported for tislelizumab versus docetaxel (41.1% vs 75.2% of Asian patients and 45.9% vs 72.9% of non-Asian patients, respectively).
Abstract 1017P –AdvanTIG-105 (NCT04047862): Ociperlimab and tislelizumab plus chemotherapy demonstrated antitumor activity in cohorts 1 and 2 of this Phase 1b dose-expansion study and the recommended Phase 2 dose showed a manageable safety profile in patients with metastatic squamous and non-squamous NSCLC.
BeiGene also shared posters describing the trial design for ongoing tislelizumab combination clinical trials:

Abstract 1194TiP – AdvanTIG-205 (NCT05014815): Phase 2 trial of ociperlimab + tislelizumab + chemotherapy in first line treatment of patients with locally advanced, unresectable, or metastatic NSCLC.
Abstract 1187TiP – BGB-A317-Sitra-301 (NCT04921358): Phase 3 study of tislelizumab with sitravatinib versus chemotherapy in patients with locally advanced/metastatic NSCLC previously treated with chemo and an anti-programmed cell death protein 1/ligand 1 antibody.
About Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

Tislelizumab is the first investigational medicine from BeiGene’s immuno-oncology biologics program and is being evaluated in solid tumor and hematologic malignancies, as monotherapy and in combination.

The global tislelizumab clinical development program includes more than 11,000 subjects enrolled to-date in 30 countries and regions. More information on the tislelizumab development program, including clinical trials and regulatory submissions, can be found on the Tislelizumab Fact Sheet in our corporate press kit.

About RATIONALE 301

RATIONALE 301 (NCT03412773) is a global, Phase 3, randomized, open-label study of tislelizumab compared with sorafenib as a first-line treatment in adult patients with unresectable HCC. The primary endpoint of the study is non-inferiority of OS between the two treatment groups. The key secondary endpoint is ORR, as assessed by Blinded Independent Review Committee (BIRC) per RECIST v1.1. Other secondary endpoints include other efficacy assessments such as PFS, DoR, and Time to Progression per BIRC, as well as measures of health-related quality of life, and safety and tolerability.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 3,300 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 16,000 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in more than 50 markets including the U.S., China, the European Union, Great Britain, Canada, Australia, and South Korea; and the non-FC-gamma receptor binding anti-PD-1 antibody, tislelizumab, as well as the PARP inhibitor, pamiparib, in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including with Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021, BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD1 antibody, tislelizumab, in North America, Europe, and Japan. Building upon this productive collaboration, BeiGene and Novartis announced an option, collaboration, and license agreement in December 2021 for BeiGene’s TIGIT inhibitor, ociperlimab, that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene will promote five approved Novartis Oncology products across designated regions of China.