On June 15, 2023 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported new data for CPI-818, the Company’s ITK inhibitor, demonstrating the potential to treat a variety of solid and hematological cancers based on a novel immunotherapy mechanism of action (Press release, Corvus Pharmaceuticals, JUN 15, 2023, View Source [SID1234632723]). The data includes updated interim results from the CPI-818 Phase 1/1b clinical trial that continues to demonstrate the potential of ITK inhibition and the absolute lymphocyte count (ALC) biomarker in T cell lymphoma (TCL). The data is being presented in a poster at the International Conference on Malignant Lymphoma (ICML) meeting, which is taking place June 13-17, 2023 in Lugano, Switzerland.

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"The CPI-818 data presented at the ICML meeting demonstrates the potential of ITK inhibition to provide a novel immunotherapy mechanism of action for cancer therapy," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "The preclinical and clinical data indicate a consistent and comprehensive rationale based on the biology and mechanism of immune enhancement resulting from selective ITK inhibition. This includes the ability to modulate normal T cell differentiation to enhance and strengthen the immune system’s ability to treat lymphomas and solid tumors. We see this in the interim tumor response data, which showed that a majority of the patients treated with the optimal dose of 200mg twice per day of CPI-818 experience tumor regression. As we consider the landscape of cancer therapy targets, ITK is not in the category of immune checkpoints, but rather it is a kinase that controls whether T cells become cancer killing cells or inflammatory cells. This positioning and the supporting research provide a strong foundation for the continued development of CPI-818 as a monotherapy and its future use in combinations with other therapies. We are excited to build upon these results and plan to meet with the U.S. FDA in the third quarter 2023 to discuss a potential registrational Phase 3 clinical trial for CPI-818 in T cell lymphoma. We also have begun planning for clinical trials with CPI-818 monotherapy in solid tumors. Overall, we have increasing confidence that CPI-818, if approved, can be a novel backbone for various immunotherapies of cancer."

CPI-818 Data Presented at ICML
The CPI-818 preclinical and clinical data was presented by Ning Ding, Ph.D. from Peking University Cancer Hospital & Institute in Beijing, China, in a poster session (abstract #193) today at the ICML meeting. The poster is available to ICML attendees in the poster hall and e-poster gallery, is also available on the Publications and Presentations page of the Corvus website. The key highlights from the poster presentation include:

Phase 1/1b Clinical Trial Interim Data
CPI-818 is currently being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed TCL. Corvus recently incorporated a minimum ALC as an eligibility criterion for enrollment in the clinical trial. Based on the current enrollment rate of the Phase 1/1b clinical trial, Corvus believes that the number of patients treated in this clinical trial would provide adequate safety and preliminary efficacy data to inform the design of a potential registrational Phase 3 randomized clinical trial. As recommended by the FDA, Corvus plans to meet with the FDA to discuss such a clinical trial; it is anticipated that this meeting will take place during the third quarter of this year.

Updated interim data as of May 18, 2023 (waterfall plot shown below): A total of 30 patients were enrolled in the Phase 1/1b trial at the optimum 200 mg two-times a day dose, including 20 evaluable for tumor response. There were 3 complete responses (CR) and 3 partial responses (PR) with one of these PRs demonstrating continued regression of the tumor. One of the patients with a CR and 2 with PRs remained on therapy. A total of ten patients remained on therapy, including six who have not had their initial tumor response evaluation. For patients with ALC above 900 per cubic milliliter of blood, objective responses (CR plus PR) were seen in 6 of 14 patients with disease control (CR, PR and stable disease) in 12 of 14 patients. No objective responses were seen in six patients (0 for 6) with ALC below 900.
Updated interim data as of May 18, 2023: In one TCL patient treated with CPI-818 for which serial tumor biopsy samples could readily be obtained, single cell RNA sequencing from paired samples comparing baseline and on-treatment specimens showed an increase in tumor infiltrating CD8+ T cells; an increase in cytolytic effector molecules such as granzymes and perforin in the T cells; and an increase in T effector memory cells (TEMRA cells), which are T cells that have responded to an antigen and are able to mediate effector functions, such as the destruction of tumor cells. In addition, flow cytometry analysis of paired blood samples comparing baseline and on treatment revealed a similar finding in both CD8 T cells and CD4 T cells. These results are consistent with preclinical data described below and support the novel immunotherapy mechanism of action of selective ITK inhibition, which is based on Th1 skewing and the resulting shift in immune response to eliminating cancer cells. Additional laboratory findings indicated that treatment with CPI-818 induces a reversal of T cells expressing exhaustion markers. T cell exhaustion is a known mechanism of resistance to checkpoint inhibitor therapy.
Figure 1: Waterfall Plot for Patients in the 200 mg Dose Cohort of the CPI-818 Phase 1/1b Clinical Trial for T Cell Lymphoma. The plot shows the best percent change in tumor volume in the 18 patients (out of 20 total evaluable patients) that were measurable by CT scan. The two other patients had cutaneous and blood involvement; one was a patient with a PR and one patient had progression.

The plot shows the best percent change in tumor volume in the 18 patients (out of 20 total evaluable patients) that were measurable by CT scan. The two other patients had cutaneous and blood involvement; one was a patient with a PR and one patient had progression.

Preclinical Data Supporting CPI-818’s Novel Immunotherapy Mechanism of Action
ITK inhibition with CPI-818 has the potential to treat solid and hematological cancers through a novel mechanism of action that has demonstrated the ability to modulate T cell differentiation and enhance the anti-tumor immune response via Th1 skewing, increased T cell cytolytic capacity and reduction of T cell exhaustion.

CPI-818 monotherapy provided statistically significant inhibition of tumor growth in established tumors in the following cancer models: EL4 TCL, A20 B cell lymphoma and CT26 colon cancer.
In the EL4 TCL model, treatment with CPI-818 led to increased infiltration of normal CD8+ T cells into the tumor. In addition, these CD8+ T cells had higher expression of perforin, an effector molecule produced by killer T cells that is involved in killing cancer cells.
In the CT26 colon cancer model, the depletion of CD8 cells reduced the efficacy of CPI-818 treatment, indicating that its mechanism of action involves the production of normal CD8+ T cells.
In the CT26 colon cancer model, treatment with CPI-818 reduced the expression of T cell exhaustion markers. T cell exhaustion is a phenomenon seen in tumors and chronic infections where prolonged exposure to antigens results in exhausted or ineffective T cell function and inability to eliminate tumors or infections.
In other murine studies using antigen primed T cells that were repeatedly stimulated, CPI-818 reduced the development of T cell exhaustion and reversed it in already exhausted T cells. These reinvigorated T cells regained their cancer cell killing capacity.
These findings indicate that the inhibition of ITK by CPI-818 produces changes in the tumor microenvironment that enhance anti-tumor immunity creating a less favorable environment for tumor growth.

On June 15, 2023 Circio Holding ASA (OSE: CRNA), a biotechnology company developing next generation RNA therapeutics, reported a general company update, demonstrating substantial progress for the company’s circRNA platform development (Press release, Circio, JUN 15, 2023, View Source [SID1234632722]).

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"Over the recent months we have accelerated the development of our unique circular RNA platform. The transition into a dedicated circRNA technology company has now been completed, with the aim to fully capture the potential of our differentiated approach and early mover advantage in this exciting new therapeutic area. The prioritization of resources to pre-clinical circRNA development over the ONCOS-102 phase 2 clinical program also significantly reduces our cash burn rate and financing needs, and allows us to fully focus our time and resources on the program that is most technologically innovative and provides the best opportunity for value creation in the short- to mid-term," said Circio’s CEO Dr. Erik Digman Wiklund.

Dr. Erik Digman Wiklund will give an online presentation to investors, analysts, and the press at 10:00 CET today (details below),

2022 year-to-date highlights
Corporate development
The new R&D strategy prioritized to accelerate the circular RNA (circRNA) platform development, a rapidly emerging area in RNA therapeutics receiving strong interest from global pharma and specialist investors
To reflect the strategic shift towards circRNA development, the name of the company was changed to Circio, under the Euronext Oslo ticker: CRNA
Chief Medical Officer Dr. Lone H Ottesen and VP Regulatory Affairs Dr. Ingunn M Lindvig have resigned to join other Nordic biotechnology companies. We thank them for their service and highly valued contributions to Circio
The organization has now been streamlined for pre-clinical development of the circRNA platform, resulting in a net staff reduction of 40%, with core scientific operations based at the Karolinska Institute in Stockholm, Sweden
Finance
Up to NOK 300m in financing over the next 3 years was secured through a convertible bond facility from Atlas Capital Markets, providing Circio flexible access to capital during a period of challenging biotech market conditions
circRNA platform development
Key technical proof-of-concept data was established for circVec, Circio’s differentiated vector delivery approach for efficient and durable circRNA expression, including demonstration of 15x extended half-life versus linear mRNA
An important patent application expanding circVec coverage to novel vector systems was filed in March, adding to the general circVec genetic cassette design filed in late 2022
Cancer gene therapy, protein replacement for rare disease and vaccines were selected as the first three therapeutic areas to be explored for circVec
Mutant KRAS platform
The first patient has been dosed in the trial in pancreatic cancer at Kansas University Cancer Center, where TG01 will be tested in combination with PD1 checkpoint inhibitor balstilimab from collaboration partner Agenus
The TG01 trial in multiple myeloma at Oslo University Hospital received regulatory approvals to proceed and the first patient has been enrolled
Important cancer vaccine data was presented by US-based biotechs at major scientific conferences, validating the clinical benefit of neoantigen cancer vaccines in post-surgical settings
Presentation

We invite to a live webcast today at 10.00 CET. Click here to join the webcast. It will be possible to submit questions during the presentation.

On June 15, 2023 BCI Pharma, in collaboration with Mithra Women’s Health, reported the anti-tumor activity of its CSF1R inhibitors in several cancer models (Press release, BCI Pharma, JUN 15, 2023, View Source [SID1234632720]). Significant tumor regression was observed either alone or in combination with a checkpoint inhibitor leading to a complete sustained tumor regression in 50% of the animals in a triple negative breast cancer model, a very aggressive form of breast cancer. These compelling results demonstrate the huge potential of BCI CSF1R inhibitors in cancer and reinforce the partnership between the two companies.

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On June 15, 2023 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported at the International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland and presented updated data from the Phase 1 ALPHA/ALPHA2 trials of ALLO-501/501A in 33 CAR T naïve patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL) treated with the Alloy manufacturing process material across different CAR T dosing and lymphodepletion regimens (Press release, Allogene, JUN 15, 2023, View Source [SID1234632717]). Earlier in June, data from the 12 patients, a subset of these 33 CAR T naïve patients, who received regimen being utilized in ongoing Phase 2 trials was presented at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"We believe these data provide strong support for the ability of our product candidates to induce durable complete remissions at a rate similar to approved autologous CD19 CAR T therapies," said Zachary Roberts, M.D., Ph.D., Executive Vice President, Research & Development and Chief Medical Officer. "The design and execution of our Phase 1 ALPHA/ALPHA 2 trials enabled a systematic evaluation of potential Phase 2 treatment regimens. Based on these data, we were able to select an optimal dosing regimen that we believe will be capable of delivering the benefit of CAR T treatment to patients without the lengthy wait time and risk of manufacturing failure associated with autologous CAR T. We have now turned our attention to enrolling our potentially pivotal Phase 2 trials as quickly as possible."

The updated analysis (data cutoff April 20, 2023) of ALPHA/ALPHA2 examined data from all 33 CAR T-naïve patients with r/r LBCL who were treated with a single infusion or consolidation therapy (two planned infusions) of ALLO-501/501A manufactured using the Alloy manufacturing process. Patients received lymphodepletion with fludarabine (30 mg/m2/day x 3 days) and cyclophosphamide (300 mg/m2/day x 3 days) and varying doses of ALLO-647 (from 13 mg/day to 30 mg/day x 3 days).

The median time from enrollment to the start of therapy was three days and 100% of patients received product per specifications. No patients received bridging therapy. The dosing breakdown for the 33 patients included in this data set is as follows:

12 patients treated with a single dose of ALLO-501/501A and FCA90 lymphodepletion (Phase 2 regimen; recap of the ASCO (Free ASCO Whitepaper) 2023 data presentation)
6 patients treated with a single dose of ALLO-501/501A and FCA<90 lymphodepletion
15 patients treated with consolidation dosing of ALLO-501/501A and split lymphodepletion
CAR T- Naïve Patients with r/r LBCL
Alloy Manufacturing Process
All
(N=33) Phase 2
Regimen (N=12) FCA<90
(N=6) Consolidation
Dosing (N=15)
Overall Response Rate (ORR), n (%) 19 (58) 8 (67) 3 (50) 8 (53)
Complete Response Rate (CR), n (%) 14 (42) 7 (58) 1 (17) 6 (40)
6 Month Complete Response, n (%) 10 (30) 5 (42) 0 5 (33)

Seven of 12 (58%) patients receiving the Phase 2 regimen achieved a CR and five (42%) maintained a CR through Month 6. Of the five patients who were in CR at 6 months, four (80%) remained in CR. The fifth patient had disease progression at 24 months. The median duration of response was 23.1 months with three patients remaining in remission for over 24 months and the longest remaining in remission for over 31 months. Across all 33 patients the CR rate was 42% with 30% maintaining a CR at Month 6. These results indicate complete responses are more common with lymphodepletion regimens containing 90 mg of ALLO-647 (FCA90). Median duration of response for both the overall population (n=33) and the patients treated with the Phase 2 regimen (n=12) was 23.1 months.

CAR T- Naïve Patients with r/r LBCL
All
(N=33) Phase 2
Regimen (N=12) FCA<90
(N=6) Consolidation
(N=15)
All Gr
N (%) Gr 3+
N (%) All Gr
N (%) Gr 3+
N (%) All Gr
N (%) Gr 3+
N (%) All Gr
N (%) Gr 3+
N (%)
CRS 8 (24) 0 4 (33) 0 1 (17) 0 3 (20) 0
Neurotoxicity 13 (39) 2 (6) 4 (33) 0 2 (33) 0 7 (47) 2 (13)
ICANS 0 0 0 0 0 0 0 0
GvHD 0 0 0 0 0 0 0 0
IRR 16 (49) 3 (9) 8 (67) 0 3 (50) 1 (17) 5 (33) 2 (13)
Infection 19 (58) 5 (15) 8 (67) 1 (8) 3 (50) 1 (17) 8 (53) 3 (20)
Prolonged Gr3+ Cytopenia - 4 (12) - 2 (17) - 0 - 2 (13)

Across the 33 patients, treatment was generally well tolerated with no incidences of Grade 3 or greater cytokine release syndrome, and no cases of immune effector cell-associated neurotoxicity syndrome or graft versus host disease. Cytopenia and infections were manageable and comparable to the experience with autologous CAR T cell therapies in patients with r/r LBCL.

The ALPHA/ALPHA2 Phase 1 trials were designed to assess the safety, tolerability, and preliminary efficacy at increasing dose levels of ALLO-501 and ALLO-501A, allogeneic CAR T cell product candidates that target CD19. In addition to exploring multiple cell doses, these studies evaluated various doses of ALLO-647, Allogene’s proprietary lymphodepleting antibody designed to prevent premature rejection of AlloCAR T cells. Allogene is currently enrolling the potentially pivotal Phase 2 ALPHA2 trial of ALLO-501A in LBCL and expects to complete enrollment in 1H2024. The Company expects to open trial sites in Europe, Canada and Australia during 2023.

About ALLO-501 and ALLO-501A
ALLO-501 and ALLO-501A are anti-CD19 AlloCAR T investigational products for the treatment of large B cell lymphoma. ALLO-501A, a next-generation anti-CD19 AlloCAR T, eliminates the rituximab recognition domains in ALLO-501, which could allow for use in a broader patient population, including NHL patients with recent rituximab exposure. This product candidate is currently being studied in an ongoing potentially pivotal Phase 2 trial. In June 2022, the U.S. Food and Drug Administration granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-501A in r/r LBCL.

On June 15, 2023 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, reported that it will present data on its Bruton’s tyrosine kinase inhibitor (BTKi) BRUKINSA (zanubrutinib) at the 17th International Conference on Malignant Lymphoma (ICML), which is taking place from June 13-17 in Lugano, Switzerland (Press release, BeiGene, JUN 15, 2023, View Source [SID1234632709]).

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"The data presented at ICML provide further evidence supporting our confidence in BRUKINSA. Notably, an updated analysis with a median follow-up of 20.2 months, reinforced previous results from the Phase 2 ROSEWOOD trial of BRUKINSA in combination with obinutuzumab," said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology. "We recently announced EMA acceptance of our filing for BRUKINSA in combination with obinutuzumab as a treatment for patients with relapsed or refractory follicular lymphoma who received at least two prior lines of therapy; and additional worldwide regulatory submissions are ongoing."

In an updated analysis from the Phase 2 ROSEWOOD trial shared as an oral presentation at ICML, BRUKINSA in combination with obinutuzumab demonstrated clinically meaningful activity and was generally well-tolerated in patients with heavily pretreated relapsed or refractory (R/R) follicular lymphoma (FL).

BRUKINSA in combination with obinutuzumab showed an overall response rate of 69.0% versus 45.8% in the obinutuzumab arm (p = 0.0012) and median follow-up of 20.2 months. The complete response rate for BRUKINSA in combination with obinutuzumab was 39.3% compared to 19.4% for obinutuzumab alone. Non-hematologic treatment-emergent adverse events of any grade that occurred more frequently (>5% difference) in the combination group were petechiae (6.3% vs. 0%) and herpes zoster infection (6.3% vs. 0%); in contrast, pyrexia (13.3% vs. 19.7%) and infusion-related reaction (2.8% vs. 9.9%) occurred more frequently in patients receiving obinutuzumab alone.

These results will be presented on June 16, 2023, 3:30 – 5:00 pm CEST. (Abstract #81)

Demonstrating a commitment to developing rigorous evidence for potential new treatments for rare hematologic malignancies, BeiGene will detail the trial design of its Phase 3 MAHOGANY study (NCT05100862) of BRUKINSA plus obinutuzumab versus lenalidomide plus rituximab in R/R FL or marginal zone lymphoma in an oral presentation during the Ongoing Trials Session. (Abstract #994)

Additional Data Further Demonstrate Safety and Efficacy Profile for BRUKINSA

At a median follow-up of 43.7 months, extended follow-up data from the pivotal Phase 3 SEQUOIA study (NCT03336333) showed BRUKINSA efficacy was maintained in patients with treatment-naïve CLL/SLL without del(17p) and patients with del(17p) receiving BRUKINSA continued to show progression-free survival (PFS) benefit consistent with the randomized cohort. Rates of atrial fibrillation remained low, and no new safety signals were identified. BRUKINSA continues to be well tolerated over time, with low rates of treatment discontinuation. (Abstract #154)

In a subgroup analysis of the Phase 3 ALPINE trial (NCT03734016), BRUKINSA showed improved PFS over ibrutinib in patients in China with R/R chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), consistent with the global study population. A favorable safety profile was also observed with BRUKINSA compared with ibrutinib, with lower rates of treatment discontinuations and serious adverse events. (Abstract #592)

Preliminary results for the CLL/SLL subgroup of an ongoing Phase 2 trial (NCT04116437) evaluating BRUKINSA in patients with various previously treated with B-cell malignancies who are intolerant to ibrutinib and/or acalabrutinib, demonstrated that treatment with BRUKINSA was well-tolerated and unlikely to lead to recurrence of intolerant adverse events experienced with prior BTK-inhibitor therapy, suggesting BRUKINSA may be a treatment option for these patients. (Abstract #345)

Initial findings from a Phase 2 trial (NCT03824483) of long-term follow-up of BRUKINSA, obinutuzumab and venetoclax (BOVen) demonstrated high rates of durable undetectable minimal residual disease (MRD) in CLL/SLL patients administered BOVen. Of the 46 patients meeting MRD criteria to cease treatment, median time from end of treatment to MRD conversion was 29.8 months. The most common grade ≥3 adverse events were neutropenia (23.1%), thrombocytopenia (7.7%), lung infection (5.8%) (Abstract #153)

More details on BeiGene’s abstracts are available in the ICML online program.

About BRUKINSA (zanubrutinib)

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies.

BRUKINSA is supported by a broad clinical program which includes more than 4,900 patients in 35 trials across 29 markets. To date, BRUKINSA is approved in more than 65 markets around the world, including the United States, China, the European Union, Great Britain, Canada, Australia, South Korea, and Switzerland. The product information may differ from country to country. Prescribers should consult the product information approved in their respective country.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher hemorrhage, including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.6% of patients treated with BRUKINSA monotherapy in clinical trials, with fatalities occurring in 0.3% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 30% of patients.

Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 24% of patients, most commonly pneumonia (11%), with fatal infections occurring in 2.9% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred. Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (22%), thrombocytopenia (8%) and anemia (7%) based on laboratory measurements, developed in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 11% of patients, and Grade 4 thrombocytopenia occurred in 2.8% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 13% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer reported in 7% of patients. Other second primary malignancies included malignant solid tumors (5%), melanoma (1.2%), and hematologic malignancies (0.5%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 3.7% of 1550 patients treated with BRUKINSA monotherapy, including Grade 3 or higher cases in 1.7% of patients. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.2% of patients.

Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

In this pooled safety population, the most common adverse reactions, including laboratory abnormalities, in ≥30% of patients who received BRUKINSA (N=1550) included decreased neutrophil count (42%), upper respiratory tract infection (39%), decreased platelet count (34%), hemorrhage (30%), and musculoskeletal pain (30%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

U.S. INDICATIONS

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with:

Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
Waldenström’s macroglobulinemia (WM)
Mantle cell lymphoma (MCL) who have received at least one prior therapy
Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen
The MCL and MZL indications are approved under accelerated approval based on overall response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Please see full U.S. Prescribing Information at www.beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at www.beigene.com/PDF/BRUKINSAUSPPI.pdf