On January 30, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported an update on the ongoing development of its product candidates, eftilagimod alpha (efti) and IMP761 for the quarter ended 31 December 2023 (Q2 FY24) (Press release, Immutep, JAN 30, 2024, View Source [SID1234639708]).

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EFTI DEVELOPMENT PROGRAM FOR CANCER

TACTI-002 (KEYNOTE-PN798) – Phase II clinical trial in first line NSCLC

Immutep reported excellent new clinical data from the TACTI-002 trial evaluating efti in combination with KEYTRUDA (pembrolizumab) at the ESMO (Free ESMO Whitepaper) Congress in October 2023. A median Overall Survival (OS) of 35.5 months was reported in first line NSCLC patients expressing PD-L1 (TPS ≥1%). Encouragingly, for patients with low PD-L1 expression (TPS 1-49%) median OS was 23.4 months, for patients with negative expression (TPS<1%) median OS was 15.5 months, and a median OS has not yet been reached in patients with high PD-L1 expression (TPS ≥50%).

New biomarker data from the trial was presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November. The data demonstrated an early increase in immune cells (absolute lymphocyte count) was linked to improved clinical outcomes including OS. Significant increases of Th1 biomarkers (IFN-gamma, CXCL-10) and RNA levels of immune activating genes were observed in patients. Similar immune response biomarkers in the blood were reported previously from Immutep’s double-blind, randomised AIPAC Phase IIb trial, which combined efti with chemotherapy alone and did not include any anti-PD-1 therapy.

TACTI-003 (KEYNOTE-PNC34) – Phase IIb clinical trial in 1st line HNSCC

Enrolment was completed for the TACTI-003 trial in November 2023. A total of 171 first line head and neck squamous cell carcinoma (1L HNSCC) patients have been enrolled in this randomized, multicenter Phase IIb trial evaluating efti in combination with pembrolizumab in 138 patients with PD-L1 positive (Combined Positive Score [CPS] ≥1) tumors (Cohort A) and in 33 patients with PD-L1 negative tumors (Cohort B).

The primary endpoint of the study is ORR of evaluable patients according to RECIST 1.1. Secondary endpoints include OS, ORR according to iRECIST, PFS, and DoR. Patients in Cohort A whose tumors express PD-L1 (CPS >1) are stratified by CPS 1-19 and CPS >20, and the clinical results for these CPS groups, as well as for patients in Cohort B with CPS <1, will be evaluated.

Immutep expects to report first data from TACTI-003 in H1 CY2024.

AIPAC-003 – Integrated Phase II/III trial in Metastatic Breast Cancer

The Company completed the safety lead-in portion of the AIPAC-003 trial evaluating for the first time 90mg of efti in combination with paclitaxel in 6 patients during the quarter. The treatment was well tolerated with no dose limiting toxicities. This good safety profile enabled the lead-in phase to be closed after the first 6 patients. Following the recommendation of the independent Data Monitoring Committee (IDMC), the Company proceeded into the randomized Phase II portion of study and is currently dosing patients. Currently 18 patients have been dosed in the randomized part.

TACTI-004 – Phase III registrational trial in 1L NSCLC

Immutep received constructive regulatory feedback from the Paul-Ehrlich-Institut (PEI), a German regulatory authority and part of the Committee for Medicinal Products for Human Use (CHMP), regarding the planned TACTI-004 trial of efti for 1L NSCLC in December. The PEI is supportive of Immutep moving ahead with the registrational trial evaluating efti in combination with an anti-PD-1 therapy in a chemotherapy-free regimen or as a triple combination approach that includes chemotherapy. Also, the PEI acknowledged the good safety profile of efti in combination with anti-PD-1 therapy.

Additional interactions with the FDA, other local European regulators, as well as with other stakeholders and potential partners are ongoing. Immutep plans to announce the final trial design for TACTI-004 in Q1 of CY2024.

INSIGHT-003 – Phase I in 1L NSCLC

Promising efficacy and tolerability data was presented from the INSIGHT-003 trial at the ESMO (Free ESMO Whitepaper) Congress 2023 in October. The trial evaluates efti plus anti-PD-1 therapy and doublet chemotherapy as first line therapy in non-squamous NSCLC patients. A strong ORR of 71.4% was reported, along with a Disease Control Rate of 90.5% and a 10.1-month median PFS. Median OS has not been reached, despite 81% of patients having low or negative PD-L1 expression.

In the difficult-to-treat PD-L1 TPS <50% patient population (i.e. those with cold or tepid tumors), the triple combination achieved a high 70.6% response rate and median PFS that exceeded 10 months in both low (TPS 1-49%) and negative (TPS<1%) PD-L1 patients, which collectively represent roughly 70% of the overall NSCLC patient population and remain an area of high unmet need.

In November, the INSIGHT-003 trial was expanded to four sites across Germany to support faster enrolment. Currently, 30 out of a total of 50 patients are enrolled. Recruitment is expected to be completed in 1H CY2024.

INSIGHT-005 – Phase I trial in Urothelial Carcinoma

The first patient was enrolled and safely dosed in the investigator-initiated INSIGHT-005 trial, following the close of the quarter in January 2024. The study is evaluating efti and the anti-PD-L1 therapy BAVENCIO (avelumab) in up to 30 patients with metastatic urothelial cancer and is jointly funded with Merck KGaA, Darmstadt, Germany.

EFTISARC-NEO – Phase II Trial in Soft Tissue Sarcoma

The EFTISARC-NEO trial continued throughout the quarter, with 9 patients now enrolled and participating. The study will evaluate efti in combination with pembrolizumab and radiotherapy in up to 40 soft tissue sarcoma (STS) patients in the neoadjuvant (prior to surgery) setting. The trial is funded by a Polish grant program and is the first chemo-free triple combination therapy of efti as well as the first to evaluate the product candidate in a neoadjuvant setting. STS is an orphan disease with high unmet medical need and poor patient prognosis. Currently, Immutep expects first clinical data to be reported in H1 of CY2024.

IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE

IMP761 is the Company’s proprietary preclinical candidate and world’s first LAG-3 agonist that aims to treat the underlying cause of multiple autoimmune diseases. Immutep is continuing its pre-clinical development and IND-enabling toxicology studies, which are necessary to evaluate the safety and toxicity of IMP761 before first-in-human trials can begin.

Immutep expects to begin the clinical development of IMP761 by mid-CY2024. Preparations for clinical development are ongoing.

PARTNER UPDATE: MONASH UNIVERSITY

Following the close of the quarter, Immutep entered into a research collaboration agreement with Monash University. The new agreement reflects an extension of the research collaboration agreements with Monash University signed in 2017 and 2020. Importantly, the new agreement will enable the parties to progress their investigations into the structure of LAG-3 and how LAG-3 interacts with its main ligand, MHC Class II. The research continues to be led by Professor Jamie Rossjohn at Monash University and Immutep’s CSO, Dr Frederic Triebel.

INTELLECTUAL PROPERTY

During the quarter, Immutep was granted a new patent for efti by the Korean Intellectual Property Office. The patent protects Immutep’s intellectual property for combination therapies comprised of efti and a chemotherapy agent which is oxaliplatin, carboplatin, or topotecan. The application was filed as a second divisional application and follows the grant of the first divisional patent, announced in 2022.

FINANCIAL SUMMARY

Immutep continued prudent cashflow management and strategic investment into its clinical trial programs for efti and preclinical program for IMP761 during the second quarter (Q2 FY24).

Immutep’s cash position remains very strong with a cash and cash equivalent balance as at 31 December 2023 of approximately $103.7 million. With an expected cash reach till early CY2026, the Company is well financed to reach key milestones that will potentially add value to efti and IMP761.

Cash receipts from customers in Q2 FY24 were $38k, compared to $132k in Q1 FY24. During the quarter, the Company received a $1.1 million cash rebate from the Australian Federal Government’s research and development (R&D) tax incentive program and a €1.6 million (~$2.6 million) R&D tax incentive payment in cash from the French Government under its Crédit d’Impôt Recherche scheme (CIR).

The net cash used in G&A activities in the quarter was $0.8 million, compared to $1.6 million in Q1 FY24.

Payments of $427k to Related Parties (detailed in Item 6 of the Appendix 4C) comprises Non-Executive Directors’ fees and Executive Directors’ remuneration.

The net cash used in R&D activities in the quarter was $6.9 million, compared to $9.7 million in Q1 FY24. The decrease in cash used for the quarter was mainly due to the following:

1)
decreased clinical trial expenses since the TACTI-002 clinical trial is in close out phase;

2)
reduced contract laboratory services compared to last quarter; and

3)
decreased efti manufacturing activity.

Payment for staff costs was $2.2 million in the quarter compared to $2.3 million last quarter.

Total net cash outflows used in operating activities in the quarter were $5.5 million compared to $12.9 million in Q1 FY24.

On January 30, 2024 HUTCHMED (China) Limited (Nasdaq/AIM:​HCM, HKEX:​13) ("HUTCHMED") reported that the marketing approval of ELUNATE (fruquintinib) by the Pharmacy and Poisons Board of Hong Kong for the treatment of adult patients with previously treated metastatic colorectal cancer ("CRC") (Press release, Hutchison China MediTech, JAN 30, 2024, View Source [SID1234639707]). ELUNATE is a selective oral inhibitor of vascular endothelial growth factor ("VEGF") receptors -1, -2 and -3, which play a pivotal role in blocking tumor angiogenesis.

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This marks the first medicine to be approved under the new mechanism for registration of new drugs ("1+" mechanism) announced by the Government of the Hong Kong Special Administrative Region ("SAR") in October last year. The mechanism officially commenced on November 1, 2023. It allows drugs which are beneficial for treatment of life-threatening or severely debilitating diseases to apply for registration for use in Hong Kong, if they have supporting local clinical data and recognition from relevant experts, when they have been approved by only one reference drug regulatory authority (instead of two otherwise). HUTCHMED submitted the application based on the approval of ELUNATE from the China National Medical Products Administration ("NMPA") supported with local clinical data. Fruquintinib was also approved by the U.S. Food and Drug Administration ("FDA") in November 2023.

"We have made it a priority to do everything we can to bring the benefits of our innovative medicines to Hong Kong, our Company’s birthplace, and are excited to have our first medicine now approved here," said Dr Karen Atkin, Executive Vice President and Chief Operating Officer of HUTCHMED. "We appreciate the streamlined drug registration process, showing the efficiency and commitment of the Hong Kong government to accelerate patient access to novel therapies. As we advance our pipeline of drug candidates in other cancer types and immunological diseases, we look forward to bringing additional therapies to benefit patients in Hong Kong."

This approval indication is for patients with metastatic CRC who have previously received fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy, and those who have previously received or are not suitable for receiving anti-VEGF therapy or anti-epidermal growth factor receptor (EGFR) therapy (RAS wild-type).

"CRC is the second most common cancer type in Hong Kong with limited effective treatment options available, especially for previously treated metastatic CRC patients," said Dr Caron Li, Vice President, Oncology and Immunology, Hong Kong and Regional Markets of HUTCHMED. "Fruquintinib, as a third-line treatment administered orally, demonstrated clinically meaningful benefits and a consistent safety profile in global clinical trials. We are honored to be the first through the "1+" mechanism and look forward to bringing this important treatment option to patients in Hong Kong as quickly as possible.

Dr Stephen Chan, an academic and a specialist in Medical Oncology, said, "Cancer remains to be a major challenge for the patients, their families and us as healthcare providers, with a rising trend in incidence over the past decades. The complex nature of cancer has made it particularly arduous for researchers to bring new advancements to the treatment. It is truly encouraging to see homegrown innovations taking on an increasingly active role to address the global unmet medical needs. We are excited to bring such meaningful treatment options to the cancer patients in Hong Kong."

Fruquintinib will be sold and marketed in Hong Kong by HUTCHMED under the brand name ELUNATE. It has been developed and commercialized in mainland China in partnership with Eli Lilly & Company. Takeda has the exclusive worldwide license to fruquintinib outside of mainland China, Hong Kong and Macau. Takeda markets fruquintinib in the United States under the brand name FRUZAQLA. Fruquintinib was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) shortly after FDA approval.

About CRC in Hong Kong

CRC is a cancer that starts in either the colon or rectum. It was the second most common cancer in Hong Kong in 2021, with about 5,900 new patients diagnosed with CRC, and associated with about 2,300 deaths.1 Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.2,3,4,5,6

About Fruquintinib

Fruquintinib is a selective oral inhibitor of VEGF receptors ("VEGFR") -1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for the potential use as part of combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combination with other anti-cancer therapies.

About Fruquintinib Approval in China

Fruquintinib was approved for marketing in China in September 2018, where it is co-marketed by HUTCHMED and Lilly under the brand name ELUNATE. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. The approval was based on data from the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, which were published in The Journal of the American Medical Association, JAMA. Since its launch in China, fruquintinib has benefited more than 80,000 colorectal cancer patients as of mid-2023.

About Fruquintinib Approval in the United States

Fruquintinib received approval in the United States in November 2023, where it is marketed by Takeda under the brand name FRUZAQLA. The approval was based on data from two large Phase III trials: the multi-regional FRESCO-2 trial, data from which were published in The Lancet, along with the FRESCO trial conducted in China. The trials investigated fruquintinib plus best supportive care versus placebo plus best supportive care in patients with previously treated mCRC. Both FRESCO and FRESCO-2 met their primary and key secondary efficacy endpoints and showed consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials.

On January 30, 2024 Bristol Myers Squibb (NYSE: BMY) reported three regulatory acceptances from the U.S. Food and Drug Administration (FDA) and Japan’s Ministry of Health, Labour and Welfare (MHLW) for Breyanzi (lisocabtagene maraleucel) (Press release, Bristol-Myers Squibb, JAN 30, 2024, View Source [SID1234639706]). In the U.S., the FDA has accepted the company’s two supplemental Biologics License Applications (sBLA) for Breyanzito expand into new indications to include the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) and relapsed or refractory mantle cell lymphoma (MCL) after a Bruton tyrosine kinase inhibitor (BTKi). The FDA has granted both applications Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of May 23, 2024 for Breyanzi in relapsed or refractory FL and May 31, 2024 for Breyanzi in relapsed or refractory MCL.

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Japan’s MHLW has also accepted Bristol Myers Squibb’s supplemental New Drug Application (sNDA) for Breyanzi for the treatment of relapsed or refractory FL.

"Patients living with follicular lymphoma and mantle cell lymphoma often experience cycles of remission and relapse with multiple lines of treatment, and we are committed to delivering innovative treatment solutions to this population," said Anne Kerber, M.D., senior vice president, Head of Late Clinical Development, Hematology, Oncology, Cell Therapy (HOCT), Bristol Myers Squibb. "Breyanzi offers the potential for durable response, and these filing acceptances in the U.S. and Japan support our commitment to delivering our best-in-class CAR T cell therapy treatments to as many eligible patients as possible."

Clinical Trials Supporting Regulatory Applications for Breyanzi in FL and MCL

In relapsed or refractory FL, the applications for Breyanzi in the U.S. and Japan are based on results from the TRANSCEND FL study, which represents the largest clinical trial to date evaluating a CAR T cell therapy in patients with relapsed or refractory indolent B cell non-Hodgkin lymphoma (NHL), including high-risk second-line FL. In the study, Breyanzi demonstrated high rates of complete responses.

In relapsed or refractory MCL, the application for Breyanzi in the U.S. is based on results from the MCL cohort of the TRANSCEND NHL 001 study, in which Breyanzi demonstrated statistically significant and clinically meaningful responses in heavily pre-treated patients, with the majority of patients achieving a complete response.

In both studies, Breyanzi demonstrated a consistent safety profile with no new safety signals reported. Results from both trials were presented at the 2023 International Conference on Malignant Lymphoma (ICML) in June 2023 and at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2023.

A sBLA for Breyanzi for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who have received a prior BTKi and B-cell lymphoma 2 inhibitor is also currently under Priority Review with the FDA with an assigned target action date of March 14, 2024.

About TRANSCEND FL

TRANSCEND FL (NCT04245839) is an open-label, global, multicenter, Phase 2, single-arm study to determine the efficacy and safety of Breyanzi in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL), including follicular lymphoma (FL) and marginal zone lymphoma. The primary outcome measure is overall response rate. Secondary outcome measures include complete response rate, duration of response, and progression-free survival.

About TRANSCEND NHL 001

TRANSCEND NHL 001 (NCT02631044) is an open-label, multicenter, pivotal, Phase 1, single-arm, seamless-design study to determine the safety, pharmacokinetics and antitumor activity of Breyanzi in patients with relapsed or refractory B-cell NHL, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, FL Grade 3B and mantle cell lymphoma. The primary outcome measures are treatment-related adverse events, dose-limiting toxicities and overall response rate. Secondary outcome measures include complete response rate, duration of response and progression-free survival.

About FL

Follicular lymphoma is the second most common, slow-growing form of NHL, accounting for 20 to 30 percent of all NHL cases. Most patients with FL are over 50 years of age when they are diagnosed. FL develops when white blood cells cluster together to form lumps in a person’s lymph nodes or organs. It is characterized by periods of remission and relapse, and the disease becomes more difficult to treat after relapse or disease progression.

About MCL

Mantle cell lymphoma (MCL) is an aggressive, rare form of non-Hodgkin lymphoma (NHL), representing roughly 3 percent of all NHL cases. MCL originates from cells in the "mantle zone" of the lymph node. MCL occurs more frequently in older adults with an average age at diagnosis in the mid-60s, and it is more often found in males than in females. In MCL, relapse after initial treatment is common, and for most, the disease eventually progresses or returns.

About Breyanzi

Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment.

Breyanzi is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with LBCL, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma grade 3B who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy, or refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant due to comorbidities or age, or relapsed or refractory disease after two or more lines of systemic therapy. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding cytokine release syndrome and neurotoxicity.

Breyanzi is also approved in Japan and Europe for the second-line treatment of relapsed or refractory LBCL, and in Japan, Europe, Switzerland, United Kingdom and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy. Bristol Myers Squibb’s clinical development program for Breyanzi includes ongoing and planned clinical studies in earlier lines of treatment for patients with relapsed or refractory LBCL and other types of lymphoma and leukemia. For more information, visit clinicaltrials.gov.

U.S. Important Safety Information

BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:

refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
relapsed or refractory disease after two or more lines of systemic therapy.
Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
Cytokine Release Syndrome (CRS)

Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Among patients receiving BREYANZI for LBCL (N=418), CRS occurred in 46% (190/418), including ≥ Grade 3 CRS (Lee grading system) in 3.1% of patients.

In patients receiving BREYANZI after two or more lines of therapy for LBCL, CRS occurred in 46% (122/268), including ≥ Grade 3 CRS in 4.1% of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 98% with a median duration of 5 days (range: 1 to 17 days).

In patients receiving BREYANZI after one line of therapy for LBCL, CRS occurred in 45% (68/150), including Grade 3 CRS in 1.3% of patients. The median time to onset was 4 days (range: 1 to 63 days). CRS resolved in all patients with a median duration of 4 days (range: 1 to 16 days).

The most common manifestations of CRS (≥10%) included fever (94%), hypotension (42%), tachycardia (28%), chills (23%), hypoxia (16%), and headache (12%).

Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.

Of the 418 patients who received BREYANZI for LBCL, 23% received tocilizumab and/or a corticosteroid for CRS, including 10% who received tocilizumab only and 2.2% who received corticosteroids only.

Neurologic Toxicities

Neurologic toxicities that were fatal or life-threatening, including immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following treatment with BREYANZI. Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, also occurred.

In patients receiving BREYANZI after two or more lines of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 35% (95/268), including ≥ Grade 3 in 12% of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of neurotoxicity was 8 days (range: 1 to 46 days). Neurologic toxicities resolved in 85% with a median duration of 12 days (range: 1 to 87 days).

In patients receiving BREYANZI after one line of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 27% (41/150) of patients, including Grade 3 cases in 7% of patients. The median time to onset of neurologic toxicities was 8 days (range: 1 to 63 days). The median duration of neurologic toxicity was 6 days (range: 1 to 119 days).

In all patients combined receiving BREYANZI for LBCL, neurologic toxicities occurred in 33% (136/418), including ≥ Grade 3 cases in 10% of patients. The median time to onset was 8 days (range: 1 to 63), with 87% of cases developing by 16 days. Neurologic toxicities resolved in 85% of patients with a median duration of 11 days (range: 1 to 119 days). Of patients developing neurotoxicity, 77% (105/136) also developed CRS. The most common neurologic toxicities (≥ 5%) included encephalopathy (20%), tremor (13%), aphasia (8%), headache (6%), dizziness (6%), and delirium (5%).

CRS and Neurologic Toxicities Monitoring

Monitor patients daily for at least 7 days following BREYANZI infusion at a REMS-certified healthcare facility for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion and treat promptly. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Manage neurologic toxicity with supportive care and/or corticosteroid as needed. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time.

BREYANZI REMS

Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:

Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
Certified healthcare facilities must have on-site, immediate access to tocilizumab.
Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.
Further information is available at www.BreyanziREMS.com, or contact Bristol-Myers Squibb at 1-888-423-5436.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).

Serious Infections

Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion.

In patients receiving BREYANZI for LBCL, infections of any grade occurred in 36% with Grade 3 or higher infections occurring in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections occurred in 4.3%, viral infections in 1.9% and fungal infections in 0.5%.

Febrile neutropenia developed after BREYANZI infusion in 8% of patients with LBCL. Febrile neutropenia may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines.

Avoid administration of BREYANZI in patients with clinically significant active systemic infections.

Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells.

In patients who received BREYANZI for LBCL, 15 of the 16 patients with a prior history of HBV were treated with concurrent antiviral suppressive therapy. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. In patients with prior history of HBV, consider concurrent antiviral suppressive therapy to prevent HBV reactivation per standard guidelines.

Prolonged Cytopenias

Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion.

Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 36% of patients with LBCL and included thrombocytopenia in 28%, neutropenia in 21%, and anemia in 6%.

Monitor complete blood counts prior to and after BREYANZI administration.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI.

In patients receiving BREYANZI for LBCL, hypogammaglobulinemia was reported as an adverse reaction in 11% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 28% of patients.

Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.

Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.

Secondary Malignancies

Patients treated with BREYANZI may develop secondary malignancies. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol-Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for developing altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 8 weeks.

Adverse Reactions

The most common nonlaboratory adverse reactions (incidence ≥ 30%) are fever, CRS, fatigue, musculoskeletal pain, and nausea.

The most common Grade 3-4 laboratory abnormalities (≥ 30%) include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease.

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.

On January 30, 2024 Breakpoint therapeutics reported that its Managing Directors Daniel Speidel and Jon Hollick will attend the DDR Inhibitors Summit 2024 in Boston (30 January- 1 February 2024) (Press release, Breakpoint Therapeutics, JAN 30, 2024, View Source [SID1234639705]). At this international meeting, experts from industry and academia gather to share and discuss updates in the development of novel therapeutics targeting the DNA Damage response in cancer cells.

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

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Daniel Speidel will chair the conference and also moderate a panel entitled "What Makes the Perfect Next-Generation DDR Inhibitor Target?". In addition, Jon Hollick will present a poster highlighting new data from Breakpoint’s PolQ programme.

On January 30, 2024 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported that it has entered into a strategic collaboration with Mass General Brigham (President and CEO: Anne Klibanski, MD) that is focused on translational medicine and early development to establish an integrated approach to scientific advancement and clinical expertise (Press release, Astellas, JAN 30, 2024, View Source [SID1234639703]).

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!

Initial projects of mutual interest will be focused in key areas of R&D investment for Astellas, including oncology, rare disease, and cell and gene therapy. Through the alliance, Astellas and Mass General Brigham aim to:

Accelerate innovation through collaborative research, as well as exploring and expanding new research frontiers.

Translate innovative research into clinical trials and actionable solutions that address serious unmet needs and aim to improve healthcare for all.

Leverage scientific and clinical expertise to inform and accelerate the development of novel therapies.
Academic collaborations are a critical component of Astellas’ innovation strategy. They underpin the company’s ongoing commitment to enhance scientific knowledge, better understand diseases and modalities, optimize clinical trials, and ultimately, transform patient care. Located in Boston, Massachusetts, Mass General Brigham is one of the leading academic medical centers in the United States. The healthcare system has extensive discovery and translational research in all areas, including oncology, rare disease, and cell and gene therapy, through its research initiatives and thematic centers, including the Gene and Cell Therapy Institute. This collaboration will leverage Mass General Brigham’s clinical and research expertise, and capabilities including clinical data and human-derived cell models.

Chris Coburn, Chief Innovation Officer, Mass General Brigham

"Industry alliances are critical to advancing novel therapies toward commercialization and bringing the ‘bench to the bedside’. This collaboration supports three critical areas of rapid clinical advancement and high patient need: oncology, rare diseases, and cell and gene therapy and reflects our commitment to advancing patient-centered research and innovation."

Tadaaki Taniguchi, MD, PhD, Chief Medical Officer, Astellas

"We are incredibly excited about this collaboration with Mass General Brigham – one of the leading biomedical research organizations in the U.S. – and the promise it represents. As a global innovation community, we face significant challenges when exploring complex, potential breakthrough modalities. Only by working alongside the most innovative institutions and experts can we find solutions that can help deliver life-changing value to patients, faster."