On June 28, 2024 Waypoint Bio (aka "Waypoint"), a biotechnology company pioneering novel cell therapies for solid tumors using in vivo spatial pooled screening technology, reported $14.5 million in seed funding led by Hummingbird Ventures with participation from other institutional investors, including Recode Ventures and pre-seed lead Fifty Years (Press release, Waypoint Bio, JUN 28, 2024, View Source [SID1234644605]).

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 FDA recently approved the first ever cell therapy for solid tumors, yet innovation in this area has been slow given the challenges of the solid tumor microenvironment and difficulty testing therapies in relevant model systems at-scale. Waypoint’s platform – which uniquely combines spatial biology with pooled screening for the purpose of drug discovery – can conduct initial screens of cell therapy designs in vivo and simultaneously measure hundreds of phenotypes at the single cell level, helping illuminate which designs work and why. This novel approach enables the simultaneous measurement of how many cell therapy candidates can navigate multiple aspects of the solid tumor microenvironment, helping guide the engineering of cell therapy designs for the treatment of historically intractable diseases, such as pancreatic cancer.

"Pooled screening is an incredibly powerful technology for drug discovery, but it’s historically been limited to measuring simple cell phenotypes, such as growth or drug resistance. This limits the technology’s value in more complex diseases where interactions between cells and their environment are key, including T cell interactions with solid tumors in cancers," said Xinchen Wang, PhD, Co-founder and CEO. "Our platform turbocharges traditional pooled screening by leveraging spatial biology to generate complex, multivariate and spatial readouts for every perturbation, helping us quickly generate novel drug candidates with a greater probability of clinical success."

"We built our platform so that we could start our discovery process directly in mouse models, skipping the in vitro step while still testing cell therapy designs at high-throughput and lower cost," said David Phizicky, PhD, Co-founder and Chief Scientific Officer. "This scale of in vivo testing allows us to screen many more innovative cell therapy designs with higher potential for clinical translatability. Using spatial biology, we’re able to read out not only which assets show efficacy in vivo, but also why these assets succeed or fail, and which assets match the phenotypes observed from patient samples. This level of detail presents a potential leap forward in cell therapy design."

Waypoint will use its seed financing toward first designing CAR T-cell therapies with superior efficacy against the tumor microenvironment, and later, Treg therapies for autoimmune diseases.

"We’re thrilled to partner with Xinchen and Dave and lead Waypoint Bio’s seed funding, which will accelerate Waypoint’s plans to develop solid tumor cell therapy designs using spatial biology at scale," said Pablo Lubroth, Investor, Hummingbird Ventures. "Waypoint Bio’s founders are part of an extremely unique subset of scientists that understand the wet lab and computational biology equally well, evidenced by how they combine an in vivo spatial pooled screening platform to generate interpretations of disease that open the door for many new therapies for underserved patients."

Waypoint Bio was co-founded by Xinchen Wang and David Phizicky, MIT alum with complementary wet and dry lab backgrounds and a shared vision for leveraging AI, automation and spatial biology to build a next-generation platform for drug discovery that could impact our treatment of intractable disease. They are joined by a team of 11 researchers, scientists and engineers, and a diverse, expert Scientific Advisory Board, comprised of:

Melina Claussnitzer, PhD, Broad Institute of Harvard & MIT
Robbie Majzner, MD, Dana-Farber Cancer Institute
Yvonne Chen, PhD, UCLA
Shantanu Singh, PhD, Broad Institute
Ron Lennox, D.Phil. MBA, Biotech entrepreneur and investor
To learn more about Waypoint Bio, including partnering and career opportunities, please visit waypointbio.com.

On June 28, 2024 Physician scientists from City of Hope, one of the largest cancer research and treatment organizations in the United States, reported that people with metastatic kidney cancer who orally took a live biotherapeutic product called CBM588 while in treatment with immunotherapy and enzymatic tyrosine kinase inhibitors experienced improved health outcomes (Press release, City of Hope, JUN 28, 2024, View Source [SID1234644604]). The phase 1 trial was published today in Nature Medicine.

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!

Microorganisms in the gut modulate the immune system. City of Hope researchers are now in discussions with the global SWOG Cancer Research Network to design a phase 2/3 trial to assess the City of Hope-identified novel use of CBM588 and microbiome modulation in people with advanced cancer. Sumanta Pal, M.D., professor and vice chair of academic affairs in City of Hope’s Department of Medical Oncology & Therapeutics Research, is slated to be co-leader of the potential phase 2/3 SWOG trial.

"We at City of Hope are the first to demonstrate a live bacterial product’s ability to improve clinical outcomes for patients with kidney cancer treated with immunotherapy. CBM588 could be exciting in cancer treatment because of its potential to enhance the efficacy of immune checkpoint inhibitor-based treatment, improve patient outcomes and modulate the gut microbiota in beneficial ways," said Pal, a City of Hope medical oncologist and corresponding author of the new study. "Ongoing and larger clinical trials are crucial to validate these benefits and address current challenges. If the positive results observed in this small trial and a previous trial with nivolumab and ipilimumab are confirmed, CBM588 could become a valuable supplement in the treatment of various cancers, particularly for patients treated with immune checkpoint inhibitors."

An estimated 44% of U.S. patients with cancer in 2018 were eligible for checkpoint inhibitor drugs, according to a JAMA Network Open article that flags the increasing trend of this percentage.

In the single-center, phase 1 trial, 30 people with metastatic kidney cancer were randomized to receive cabozantinib, an inhibitor of vascular endothelial growth factor receptor, and targeted immunotherapy nivolumab with or without CBM588 as first-line treatment. Participants’ gut microbiome were analyzed via stool samples in the beginning for a baseline and then 13 weeks into treatment.

City of Hope has granted an exclusive worldwide license to Osel for intellectual property on the novel use of CBM588 to enhance the efficacy of checkpoint inhibitors used to treat cancer, including metastatic renal cell carcinoma. Scientists from Osel and Miyarisan Pharmaceutical Co. Ltd, the manufacturer of CBM588, collaborated on the study.

To date, many studies on lung cancer, melanoma and metastatic kidney cancer, among other diseases, have shown that the composition of the gut microbiome could predict immunotherapy outcomes for patients with cancer. Current guidelines for metastatic renal cell carcinoma (kidney cancer) recommend that newly diagnosed patients receive either dual checkpoint inhibitor therapy or a combination of immunotherapy and tyrosine kinase inhibitor, but most patients eventually experience disease progression while on treatment. Positive patient outcomes usually do not last, and subsequent treatments are largely palliative rather than curative. So, physician scientists are looking to combine current strategies with new treatments that do not introduce toxic side effects, such as through microbiome modulation.

In the trial, City of Hope researchers observed an increase in the abundance of unclassified Ruminococcaceae genera, which has been linked with improved clinical outcomes with immune checkpoint inhibitors in recent studies. Clostridium butyricum MIYAIRI 588, the bacterium in CBM588, produces butyric acid, which is critical for intestinal health and is a well-known immunomodulator.

"While not yet part of standard cancer treatment protocols, microbiome modulation is a promising area of research with the potential to enhance the efficacy of cancer therapies, particularly immunotherapies. Current applications are primarily within clinical trials, but the growing body of evidence suggests that microbiome-based interventions may soon become a valuable component of cancer treatment strategies," said Hedyeh Ebrahimi, M.D, M.P.H., City of Hope postdoctoral medical oncology fellow and first author of the study.

City of Hope is accelerating its research on the direct link between a healthy gut and the effectiveness of immune therapies, such as CAR T cell therapy. Its enhanced microbiome program spans from basic to clinical research and includes studying the gut microbiome’s role in protecting transplant patients from complications experienced during their recovery.

"This study demonstrates again that the microbiome has an important role in the efficacy and toxicity of cancer immunotherapy and can be targeted to improve outcome," said Marcel van den Brink, M.D., Ph.D., president of City of Hope Los Angeles and City of Hope National Medical Center, and the Deana and Steve Campbell Chief Physician Executive Distinguished Chair.

The Nature Medicine study entitled "Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial" was supported by Exelixis Inc. (XL184-IST123). CBM588 was supplied by Miyarisan Pharmaceutical Co., Ltd. and Osel Inc.

On June 28, 2024 Shorla Oncology (‘Shorla’), a U.S.-Ireland specialty pharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has approved the company’s New Drug Application (NDA) for TEPYLUTE, a ready-to-dilute formulation to treat breast and ovarian cancer in an easier to prepare, injectable product that enables dosing accuracy (Press release, Shorla Oncology, JUN 28, 2024, View Source [SID1234644603]).

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 approval fulfills an unmet need by addressing the shortcomings and handling complexities of the current lyophilized powder formulation," said Sharon Cunningham, Chief Executive Officer and Co-Founder of Shorla Oncology. "We have taken a vital oncology drug and made it easier for oncology clinics and hospitals to use, while also reducing medical personnel exposure to a hazardous drug."

TEPYLUTE, formerly SH-105, is the third FDA-approved drug for Shorla, and a significant milestone for the company as it seeks approval for several cancer-fighting drugs for the U.S. market.

"The approval of TEPYLUTE represents an important milestone for Shorla as our first in-house developed NDA," said Orlaith Ryan, Chief Technical Officer and Co-Founder of Shorla Oncology.

TEPYLUTE is a liquid form of a well-established, standard of care oncology drug, thiotepa. The new formulation eliminates the need for complex and time-consuming reconstitution. It provides consistent dosing accuracy and allows for "just in time" preparation.2

"Among TEPYLUTE’s many benefits, it removes the necessity to reconstitute which can introduce additional risks of drug preparation errors," emphasized Rayna Herman, Chief Commercial Officer. "We look forward to providing an update on our launch plans for TEPYLUTE in the near future."

The American Cancer Society estimates that more than 300,000 women will be diagnosed with breast cancer in the U.S in 2024.3 About 19,680 women will be diagnosed with ovarian cancer in the United States.4

Shorla Oncology is currently marketing two products with a robust pipeline including SH-201, the first palatable oral liquid treatment for certain forms of leukemia and other cancers. In April, the company announced the FDA had accepted SH-201 for an NDA review with an expected action date of November 30, 2024.

On June 28, 2024 Sirnaomics Ltd. (the "Company", together with its subsidiaries, the "Group" or "Sirnaomics"; stock code: 2257), a leading biopharmaceutical company engaging in discovery and development of advanced RNAi therapeutics, reported that the Group has completed STP707 Phase I clinical study with strong safety profile and stable disease activity for treatment of pancreatic cancer patients (Press release, Sirnaomics, JUN 28, 2024, View Source [SID1234644602]). This is a dose escalation study conducted in 11 oncology clinics in the U.S. The study involved six cohorts, consisting of 50 patients with various cancers, of which 11 had pancreatic cancer.

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!

In an earlier news release from the Company in August 2023, the Group noted completion of all dosing regimens for its Phase I study of STP707 for the treatment of multiple solid tumors. This basket study has enrolled patients suffering from various types of late-stage cancers and failing after multiple rounds of treatments. The study is to evaluate the safety, tolerability and anti-tumor activity of the Group’s siRNA (small interfering RNA) drug candidate, STP707, through intravenous infusion (IV) with six cohorts of escalating doses. Patients including pancreatic, colorectal, liver, melanoma and other cancers, with advanced/ metastatic or surgically unresectable solid tumors, refractory to standard therapy, were recruited. Six dose levels (3mg, 6mg, 12mg, 24mg, 36mg and 48mg) were explored in ascending doses. Patients received IV infusion on Day 1, 8, 15 and 22 of a 28-days cycle.

11 pancreatic patients (five males and six females, average age 64 years) were enrolled in the study. Patients were heavily pre-treated and received, on average, three lines of therapy prior to enrollment in the study (including Gemcitabine, Paclitaxel and Folfirinox). The preliminary results indicated that the mean treatment cycles completed was three cycles (average 12 doses). The average days for stable disease for all 11 patients with STP707 treatment was 92 days, while 31 days for the 12mg group, 65 days for 24mg group and 112 days for 48mg group, including one patient ongoing at 281 days. No treatment related adverse events (TRAE) were reported for the 11 patients, except for one patient with a Grade 2 infusion reaction. Non-treatment related adverse events were secondary to their advanced metastatic disease including intestinal obstruction, abdominal distention, gastrointestinal obstruction, embolism, gastrointestinal hemorrhage, tumor pain, hypoxia and dyspnea.

The maximum tolerated dose of STP707 for all 50 late-stage cancer patients was not reached even at 48mg dosage level. STP707 was very well-tolerated in a heavily pretreated cancer patient population. The 11 pancreatic subset of patients showed low toxicity and relatively long stable disease at various dosages (106, 281 and 302 days), and warrants further study with STP707 alone or in combination with immune check point inhibitors, given the preclinical documented ability of STP707 to recruit T-cells to the tumor microenvironment (TME). This is the first time a polypeptide nanoparticle-based siRNA cancer therapeutic has demonstrated early positive safety and efficacy results for the treatment of late-stage pancreatic cancer patients.

"We are very excited to see STP707, our leading siRNA drug product for the treatment of heavily pre-treated pancreatic cancer (one of the deadliest tumor types), shows these strong results upon intravenous administration. This is a very promising result for RNAibased cancer therapeutics for the treatment of metastasized tumors." said Dr. Patrick Lu, Ph.D., Founder, Chairman of the Board, Executive Director, President and Chief Executive Officer of Sirnaomics. "The strong safety profile, long-lasting stable disease efficacy and dose-dependent antitumor activity of this intravenously administered STP707 formulation, present a potential novel cancer therapeutic, either as a single drug or in combination with immune check point inhibitor drugs."

For more information about Sirnaomics’ clinical trials please visit ClinicalTrials.gov (Identifier NCT05037149) and the Company’s website at www.sirnaomics.com.

About STP707

STP707 is composed of two siRNA oligonucleotides, targeting TGF-β1 and COX-2 mRNA respectively, formulated in nanoparticles with a Histidine-Lysine Co-Polymer (HKP+H) peptide as the carrier. The specific carrier peptide is distinct from the carrier used in Sirnaomics’ STP705 product. Each individual siRNA was demonstrated to inhibit the expression of their target mRNAs and combining the two siRNA’s produces a synergistic effect that diminishes pro-inflammatory factors. Over-expression of TGF-β1 and COX-2 have been well-characterized in playing key regulatory roles in tumorigenesis. In preclinical studies with STP707, IV administration resulted in knock-down of TGF-β1 and COX-2 gene expressions in various organs including liver, lung and xenograft tumor. In addition, in preclinical models STP707 had shown strong antitumor activity in various solid tumor types. Using a mouse liver orthotopic tumor model, a combination regimen of STP707 with an immune checkpoint antibody has demonstrated a potent antitumor activity.

On June 28, 2024 AbbVie (NYSE: ABBV) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the conditional marketing authorization of epcoritamab (TEPKINLY), the first and only T-cell engaging bispecific antibody administered subcutaneously (under the skin), as a monotherapy for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more prior therapies (Press release, AbbVie, JUN 28, 2024, View Source [SID1234644601]). The European Commission decision on this indication for epcoritamab is anticipated later this year.

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!

"Patients with follicular lymphoma are likely to face disease recurrence and shorter durability of response with each subsequent line of treatment. This positive opinion recognizes the unmet need in the European Union for individuals with relapsed or refractory follicular lymphoma, following failure of other therapies," said Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie.

FL is typically an indolent (or slow-growing) form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes and is the second most common form of NHL accounting for 20-30% of all cases.1 In 2023, there were an estimated 13,000 cases of FL in Western Europe.2 FL is considered incurable with current standard of care therapies.3

The CHMP opinion is supported by overall and complete response data from the Phase 1/2 EPCORE NHL-1 clinical trial in 128 patients with R/R FL treated with epcoritamab after two or more lines of prior therapy. The study included patients who were refractory to both anti-CD20 monoclonal antibody therapy and an alkylating agent, patients who were refractory to last prior treatment, and patients whose disease progressed within two years of first systemic therapy. The safety profile of epcoritamab in the pivotal cohort was similar to reports of epcoritamab monotherapy in the pivotal EPCORE NHL-1 diffuse large B-cell lymphoma (DLBCL) cohort.4

An additional cohort of 86 patients evaluated a 3-step-up dosing (SUD) schedule to reduce the incidence and severity of cytokine release syndrome (CRS), which is an associated adverse effect from immune-engaging cancer treatments. For the first full dose of this 3-step regimen, mandatory hospitalization was not required. In this cohort, the incidence of CRS was 49% (42 of 86 patients; 9% were grade 2). There were no grade 3 or higher CRS events. The data from this optimization cohort of the EPCORE NHL-1 study were recently published in the Lancet Haematology.

"Each year, thousands of people in Europe are diagnosed with follicular lymphoma, and it’s an upsetting reality that many of them will experience relapse and refractory disease," said Catherine Thieblemont, M.D., Ph.D., head of the hemato-oncology department, Paris University, Hôpital Saint-Louis Assistance-Publique-Hopitaux de Paris (APHP) in Paris. "Patients deserve new treatment options, and this positive opinion is the first step to bringing epcoritamab to more patients who need it."

Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the investigational R/R FL indication and additional approvals for the R/R DLBCL indication.

About the Phase 1/2 EPCORE NHL-1 Trial
EPCORE NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a dose escalation part; an expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin’s lymphoma (B-NHL), including FL. In the expansion part, additional patients were enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who have limited therapeutic options. The optimization part evaluates the potential for alternative step-up dosing regimens to help further minimize Grade 2 cytokine release syndrome (CRS) and mitigate Grade ≥3 CRS. The primary endpoint of the expansion part was ORR as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints. The primary endpoint of the optimization part was the rate of ≥ Grade 2 CRS events and all grade CRS events from first dose of epcoritamab through 7 days following administration of the second full dose of epcoritamab.

Topline results of the study were shared in December 2023. More information can be found on www.clinicaltrials.gov (NCT03625037).

About Follicular Lymphoma (FL)
FL is typically an indolent (or slow-growing) form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes and is the second most common form of NHL accounting for 20-30% of all cases.1 FL is considered incurable with current standard of care therapies.3 Patients often relapse and with each relapse, the remission and time to next treatment is shorter.5 Over time, transformation to DLBCL, an aggressive form of NHL associated with poor survival outcomes, can occur in more than 25% of FL patients.6

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.7

Epcoritamab (approved under the brand name EPKINLY in the United States and TEPKINLY in the European Union) has received regulatory approval in certain lymphoma indications in several countries.

AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets. Both Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy and in combination across lines of therapy in a range of hematologic malignancies. Please visit clinicaltrials.gov for more information.

EU Indications and Important Safety Information about Tepkinly▼(epcoritamab)

Indications
Tepkinly (epcoritamab) as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.

Important Safety Information

Contraindications
Hypersensitivity to the active substance or to any of the excipients.

Special warnings and precautions for use
Cytokine release syndrome (CRS)
CRS, which may be life-threatening or fatal, occurred in patients receiving Tepkinly. The most common signs and symptoms of CRS include pyrexia, hypotension and hypoxia. Other signs and symptoms of CRS in more than two patients include chills, tachycardia, headache and dyspnoea.

Most CRS events occurred in Cycle 1 and were associated with the first full dose of Tepkinly. Administer prophylactic corticosteroids to mitigate the risk of CRS. Patients should be monitored for signs and symptoms of CRS following Tepkinly administration. Patients should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of CRS. At the first signs or symptoms of CRS, institute treatment of supportive care with tocilizumab and/or corticosteroids as appropriate. Patients should be counselled on the signs and symptoms associated with CRS and patients should be instructed to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time. Management of CRS may require either temporary delay or discontinuation of Tepkinly based on the severity of CRS.

Immune effector cell-associated neurotoxicity syndrome (ICANS)
ICANS, including a fatal event, have occurred in patients receiving Tepkinly. ICANS may manifest as aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, seizures, and cerebral oedema. The majority of cases of ICANS occurred within Cycle 1 of Tepkinly treatment, however some occurred with delayed onset. Patients should be monitored for signs and symptoms of ICANS following Tepkinly administration. Patients should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of ICANS. At the first signs or symptoms of ICANS treatment with corticosteroids and non-sedating-anti-seizure medicinal products should be instituted as appropriate. Patients should be counselled on the signs and symptoms of ICANS and that the onset of events may be delayed. Patients should be instructed to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time. Tepkinly should be delayed or discontinued as recommended.

Serious infections
Treatment with Tepkinly may lead to an increased risk of infections. Serious or fatal infections were observed in patients treated with Tepkinly in clinical studies. Administration of Tepkinly should be avoided in patients with clinically significant active systemic infections. As appropriate, prophylactic antimicrobials should be administered prior to and during treatment with Tepkinly. Patients should be monitored for signs and symptoms of infection, before and after Tepkinly administration, and treated appropriately. In the event of febrile neutropenia, patients should be evaluated for infection and managed with antibiotics, fluids and other supportive care, according to local guidelines.

Tumour Lysis Syndrome (TLS)
TLS has been reported in patients receiving Tepkinly. Patients at an increased risk for TLS are recommended to receive hydration and prophylactic treatment with a uric acid lowering agent. Patients should be monitored for signs or symptoms of TLS, especially patients with high tumour burden or rapidly proliferative tumours, and patients with reduced renal function. Patients should be monitored for blood chemistries and abnormalities should be managed promptly.

Tumour flare
Tumour flare has been reported in patients treated with Tepkinly. Manifestations could include localized pain and swelling. Consistent with the mechanism of action of Tepkinly, tumour flare is likely due to the influx of T-cells into tumour sites following Tepkinly administration. There are no specific risk factors for tumour flare that have been identified; however, there is a heightened risk of compromise and morbidity due to mass effect secondary to tumour flare in patients with bulky tumours located in close proximity to airways and/or a vital organ. Patients treated with Tepkinly should be monitored and evaluated for tumour flare at critical anatomical sites.

CD20-negative disease
There are limited data available on patients with CD20-negative DLBCL treated with Tepkinly, and it is possible that patients with CD20-negative DLBCL may have less benefit compared to patients with CD20- positive DLBCL. The potential risks and benefits associated with treatment of patients with CD20- negative DLBCL with Tepkinly should be considered.

Immunisation
Live and/or live-attenuated vaccines should not be given during Tepkinly therapy. Studies have not been conducted in patients who received live vaccines.

Fertility, pregnancy and lactation
Tepkinly is not recommended during pregnancy and in women of childbearing potential not using contraception.

Effects on ability to drive and use machines
Tepkinly has minor influence on the ability to drive and use machines. Due to the potential for ICANS, patients should be advised to exercise caution while (or avoid if symptomatic) driving, cycling or using heavy or potentially dangerous machines.

Undesirable effects
Summary of the safety profile
The most common adverse reactions (≥ 20%) were CRS, fatigue, neutropenia, injection site reactions, musculoskeletal pain, abdominal pain, pyrexia, nausea, and diarrhoea.

Serious adverse reactions occurred in 52% of patients. The most frequent serious adverse reaction (≥ 10%) was cytokine release syndrome (31%). Seven patients (4.2%) experienced a fatal adverse reaction (pneumonia in 3 (1.8%) patients, viral infection in 3 (1.8%) patients, and ICANS in 1 (0.6%) patient). Adverse reactions that led to discontinuation occurred in 6.6% of patients. Discontinuation of Tepkinly due to pneumonia occurred in 6 (3.6%) patients, viral infection in 3 (1.8%) patients, and CRS, ICANS, or fatigue in 1 (0.6%) patient each. Dose delays due to adverse reactions occurred in 32% of patients. Adverse reactions leading to dose delays (≥ 3%) were viral infections (9.6%), CRS (7.2%), neutropenia (4.8%), pyrexia (3.0%), and thrombocytopenia (3.0%).

This is not a complete summary of all safety information.

See Tepkinly full Summary of Product Characteristics (SmPC) at www.ema.europa.eu

Globally, prescribing information varies; refer to the individual country product label for complete information.