On March 18, 2025 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on developing innovative CAR T-cell therapies, reported its 2024 Annual Results (Press release, Carsgen Therapeutics, MAR 18, 2025, View Source [SID1234651243]).

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Business Highlights

Zevor-cel was approved by China’s National Medical Products Administration (NMPA).
As of December 31, 2024, certification and filings for zevor-cel completed in 23 provinces or cities, covering over 200 healthcare institutes; CARsgen has received a total of 154 valid orders from its commercialization partner Huadong Medicine.
Satri-cel ST-01 confirmatory Phase II trial for gastric cancer in China: enrollment has been completed, and the study has met its primary endpoint. Satri-cel received BTD designation from CDE of China NMPA. CARsgen plans to submit a New Drug Application (NDA) to the China NMPA during the first half of 2025.
Results from the investigator-initiated trial (IIT) of satri-cel were published in Nature Medicine and at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting.
The results of the IIT of an allogeneic BCMA-targeting CAR-T product CT0590, which deploys the THANK-uCAR technology platform, were presented at the 2024 ASH (Free ASH Whitepaper) Annual Meeting.
Developed THANK-u Plus platform as an enhanced version of THANK-uCAR allogeneic CAR-T platform. Multiple allogeneic CAR-T products in development, covering treatment areas such as hematologic malignancies, solid tumors, and autoimmune diseases.
Introduced Zhuhai SB Xinchuang to accelerate allogeneic CAR-T development in mainland China.
Cash and bank balances were around RMB1,479 million as of December 31, 2024. Cash and cash equivalents and deposits at the end of 2025 are expected to be not less than RMB1,080 million. Expect to have adequate cash into the 2028.
"In 2024, CARsgen achieved its first drug commercialization and made remarkable progresses in key pipeline products and technological innovations. Looking ahead, we will continue developing innovative CAR T-cell therapies to address the significant unmet medical needs," said Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics.

Zevor-cel: Approved by the NMPA and Launched in China

Zevorcabtagene autoleucel (zevor-cel, R&D code: CT053) is an autologous fully human CAR T-cell product against B-cell maturation antigen (BCMA). On February 23, 2024, zevor-cel was approved by China’s NMPA for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have progressed after at least 3 prior lines of therapy (including a proteasome inhibitor and an immunomodulatory agent). CARsgen entered into a collaboration agreement with Huadong Medicine for the commercialization of zevor-cel in mainland China. As of December 31, 2024, certification and regulatory filings for zevor-cel have been completed in 23 provinces or cities, covering over 200 healthcare institutes and we have received a total of 154 valid orders from Huadong Medicine.

Updated results of the pivotal Phase II registrational trial of zevor-cel in China were reported as an oral presentation at the 29th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress, and a subgroup analysis was presented a poster at the 66th ASH (Free ASH Whitepaper) annual congress. We anticipate that growth of sales revenue of zevor-cel will further accelerate with continuous marketing activities and broader insurance coverage.

Satri-cel: Confirmatory Phase II trial Met Primary Endpoint, Plans to Submit an NDA

Satri-cel is an autologous CAR T-cell product candidate against the protein Claudin18.2 that has the potential to be first-in-class globally. Satri-cel targets Claudin18.2 positive solid tumors with a primary focus on gastric cancer/gastroesophageal junction cancer (GC/GEJ) and pancreatic cancer (PC). Patient enrollment has been completed in confirmatory Phase II trial in China (NCT04581473) in advanced GC/GEJ. The study has met its primary endpoint of a statistically significant improvement in progression-free survival (PFS) as assessed by the Independent Review Committee (IRC). Patients treated with satri-cel infusion achieved statistically significant improvement in PFS compared to those treated with physician’s choice (paclitaxel, docetaxel, irinotecan, apatinib, or nivolumab). Based on the confirmatory Phase II clinical data, satri-cel has been granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of China NMPA.

CARsgen plans to submit an NDA to the NMPA in China during the first half of 2025. Satri-cel is expected to become the world’s first CAR-T therapy for solid tumors to be approved for market.

Updated results from the investigator-initiated trial (CT041-CG4006, NCT03874897) were published in Nature Medicine in June 2024 and presented orally at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2024. Additionally, more research findings have been published in prestigious academic journals such as the Journal of Clinical Oncology and the Journal for ImmunoTherapy of Cancer.

A Phase I clinical trial for PC adjuvant therapy (CT041-ST-05, NCT05911217), and an investigator-initiated trial for GC/GEJ adjuvant therapy (CT041-CG4010, NCT06857786) are ongoing in China.

Advancing the Development of Allogeneic CAR-T Products

In addition to autologous products, CARsgen has also been advancing differentiated allogeneic CAR T-cell products utilizing the proprietary THANK-uCAR platform. CARsgen has recently developed the THANK-u Plus platform as an enhanced version of its proprietary THANK-uCAR allogeneic CAR-T technology to address the potential impact of NKG2A expression levels on therapeutic efficacy.

The results of the IIT proof-of-concept study of an allogeneic BCMA-targeting CAR T-cell product candidate CT0590, which deploys the THANK-uCAR technology platform, were presented as a poster at the 66th ASH (Free ASH Whitepaper) Annual Meeting in December 2024. The data indicates that CT0590 has achieved a DoR of over 20 months in patients with sCR, with a peak CAR copy number exceeding 280,000 copies/µg gDNA, which is comparable to autologous BCMA CAR-T therapies, preliminarily demonstrating the durability of its efficacy.

In addition, there are several universal CAR-T products under development, covering areas such as hematologic malignancies, solid tumors, and autoimmune diseases:

CT059X: Targeting BCMA, for the treatment of R/R MM and R/R PCL. The first patient in the IIT achieved sCR at the Day-28 assessment.
KJ-C2219: Targeting CD19/CD20, for the treatment of B-cell malignancies, as well as SLE and SSc. The IITs are ongoing.
KJ-C2320: Targeting CD38, for the treatment of AML. The IIT is ongoing.
KJ-C2114: For the treatment of solid tumors.
KJ-C2526: Targeting NKG2DL, for the treatment of AML, other malignancies, and senescence.
On February 25, 2025, CARsgen announced reaching agreements with an investment fund managed by Zhuhai Hengqin SB Xinchuang Equity Investment Management Enterprise (Limited Partnership) ("Zhuhai SB Xinchuang") to jointly invest in UCARsgen Biotech Limited ("UCARsgen"), to accelerate allogeneic CAR-T development in mainland China. Under the agreements, UCARsgen has secured the exclusive rights in mainland China for the research, development, manufacture, and commercialization of the following allogeneic CAR-T products from CARsgen Therapeutics: the BCMA-targeted allogeneic CAR-T cell therapy for the treatment of multiple myeloma and plasma cell leukemia and the CD19/CD20 dual-targeted allogeneic CAR-T cell therapy for the treatment of B-cell malignancies. An investment fund managed by Zhuhai SB Xinchuang (currently undergoing registration and filing procedures) subscribed to the newly increased registered capital of UCARsgen for a consideration of RMB 80,000,000, thus retaining an 8% equity stake in the registered capital of UCARsgen upon completion of the transaction, equity stake of CARsgen Therapeutics in UCARsgen will be diluted from 100% to 92%.

Financial Highlights

The revenue was around RMB39.4 million for the year ended December 31, 2024 mainly from zevor-cel, in which was calculated on the basis of ex-works price, rather than end-of-market prices. Our revenue is recognized upon completion of ex-works delivery of products. Besides, the Company received a milestone payment of RMB75 million from Huadong Medicine for zevor-cel for the year ended December 31, 2024. Due to the inherent time cycle of CAR-T manufacturing, there is a discrepancy between the number of orders obtained from Huadong Medicine and number of ex-works deliveries. The gross profit was around RMB14.8 million for the year ended December 31, 2024, with the selling and distribution expenses around RMB0.88 million. In the commercialization stage, we are demonstrating a strong cost competitive advantage, which is mainly due to self-manufacture for plasmids and vectors with stable output and high yield per batch.

Cash and bank balances were around RMB1,479 million as of December 31, 2024. Cash and cash equivalents and deposits at the end of 2025 are expected to be not less than RMB1,080 million. We expect to have adequate cash into the 2028 excluding subsequent cash inflows.

On March 18, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, and HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13), reported that the FRUSICA-2 Phase 2/3 clinical trial evaluating sintilimab in combination with fruquintinib as second-line treatment for locally advanced or metastatic renal cell carcinoma (RCC) in China has met its primary endpoint of progression free survival (PFS) per RECIST 1.1 as assessed by blinded independent central review (BICR) (Press release, Innovent Biologics, MAR 18, 2025, View Source [SID1234651242]).

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The combination of sintilimab and fruquintinib received conditional approval from China’s National Medical Products Administration (NMPA) for the treatment of patients with advanced endometrial cancer with Mismatch Repair proficient (pMMR) tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation, based on data from the FRUSICA-1 study (NCT03903705).

The FRUSICA-2 study is a randomized, open-label, active-controlled study to evaluate the efficacy and safety of sintilimab in combination with fruquintinib versus axitinib or everolimus monotherapy for the second-line treatment of advanced RCC (NCT05522231). In addition to the primary endpoint PFS, the combination also demonstrated improvements in secondary endpoints, including objective response rate (ORR) and duration of response (DoR). Full results will be submitted for presentation at an upcoming scientific conference.

Prof Dingwei Ye of Fudan University Shanghai Cancer Center and the co-leading Principal Investigator of the FRUSICA-2 study, said: "The rapid advancements in targeted therapies, immunotherapies, and their combination regimens have led to a significant evolution in the treatment landscape for advanced renal cell carcinoma. Targeted therapy remains an indispensable and crucial component in systemic treatment of advanced RCC in China. Optimizing the selection of targeted therapy, either as monotherapy or in combination with immunotherapy, for individual patients is a key focus of clinical interest. The results from the FRUSICA 2 study underscore the potential of the sintilimab and fruquintinib combination to address the pressing medical needs of patients with this challenging disease."

Prof Zhisong He of Peking University First Hospital and the co-leading Principal Investigator of the FRUSICA-2 study, said: "The positive results from this Phase 3 study of the sintilimab and fruquintinib combination represent a significant advancement in the treatment of advanced renal cell carcinoma. We are optimistic about the clinical implications of the findings as we strive to provide more effective treatment options for patients who may not have had adequate responses to previous therapies."

Dr Hui Zhou, Senior Vice President of Innovent, stated: "We are encouraged by the positive results in the FRUSICA-2 clinical trial. These outcomes not only underscore the great potential of the combination therapy of sintilimab and fruquintinib but also bring new hope to previously treated patients with advanced renal cell carcinoma. We look forward to working closely with HUTCHMED to jointly advance the registrational communication of this innovative combo therapy and make it available to patients as soon as possible."

Dr Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED, stated: "The encouraging results from our study provide clear evidence for the combination of fruquintinib and sintilimab as a viable new treatment option for advanced renal cell carcinoma patients who have progressed on previous therapy. This not only reaffirms our commitment to advancing cancer therapies but also represents an important step forward in addressing unmet medical needs within this patient population. I extend my heartfelt gratitude to the patients and investigators who participated in this research; their contributions have been vital to our success. We look forward to sharing detailed findings with regulatory authorities and progressing toward NDA filings in the coming months."

About Kidney Cancer and RCC

It is estimated that approximately 435,000 new patients were diagnosed with kidney cancer worldwide in 2022.[i] In China, an estimated 74,000 new patients were diagnosed with kidney cancer in 2022.[ii] Approximately 90% of kidney tumors are RCC.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells.[iii]

In China, sintilimab has been approved and included in the updated NRDL for seven indications. The updated NRDL reimbursement scope for TYVYT (sintilimab injection) includes:

For the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy;
For the first-line treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
For the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer who progressed after EGFR-TKI therapy;
For the first-line treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
For the first-line treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
For the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
For the first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
Furthermore, sintilimab’s eighth indication, in combination with fruquintinib for the treatment of patients with advanced endometrial cancer with pMMR tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation, was conditional approved by the NMPA in December 2024. And the NDA for sintilimab in combination with ipilimumab as neoadjuvant treatment for resectable MSI-H/dMMR colon cancer is under the NMPA review and has been granted Priority Review designation.

In addition, three clinical studies of sintilimab have met their primary endpoints:

Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
Phase 3 study of sintilimab monotherapy as second-line treatment for squamous non-small cell lung cancer with disease progression following platinum-based chemotherapy;
Phase 2/3 study of sintilimab in combination with fruquintinib versus axitinib or everolimus monotherapy for the second-line treatment of advanced RCC.
About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three vascular endothelial growth factor (VEGF) receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy.[iv]

About Fruquintinib Approvals

Fruquintinib is co-developed and co-marketed in China by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE. It is approved for the treatment of patients with metastatic colorectal cancer 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) in China. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib.

The combination of ELUNATE (fruquintinib) and TYVYT (sintilimab injection) has conditional approval in China for the treatment of patients with advanced endometrial cancer with Mismatch Repair proficient (pMMR) tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation.

Takeda holds the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside mainland China, Hong Kong and Macau, marketing it under the brand name FRUZAQLA. Fruquintinib received approval for the treatment of previously treated metastatic colorectal cancer in the US in November 2023, in the EU in June 2024, in Switzerland and Argentina in August 2024, in Canada, Japan and the United Kingdom in September 2024, in Australia and Singapore in October 2024 and in Israel and the United Arab Emirates in December 2024. Regulatory applications are progressing in many other jurisdictions.

The global regulatory submissions are based on data from two large, randomized, controlled Phase III trials in colorectal cancer, the global, multi-regional FRESCO-2 trial and the FRESCO trial conducted in China, showing consistent benefit among a total of 734 metastatic colorectal cancer patients treated with fruquintinib. Safety profiles were consistent across trials. Results from the FRESCO-2 trial were published in The Lancet in June 2023,[v] while results from the FRESCO trial were published in The Journal of the American Medical Association, JAMA.[vi]

The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated:

About Fruquintinib for Second-line Treatment of RCC

The U.S. Food and Drug Administration (FDA) has approved five immune-oncology combination therapies for the first-line treatment of advanced RCC. However, only one immune-oncology combination therapy has been approved in China for advanced RCC patients classified as having intermediate or poor risk by the International mRCC Database Consortium (IMDC). Single-agent targeted therapy continues to be one of the primary choices for first-line treatment of advanced RCC in China. Notably, advanced RCC patients who have experienced failure with single-agent targeted therapy previously still indicate an unmet medical need.

Results from a proof-of-concept Phase Ib/II study of fruquintinib plus sintilimab were published in Targeted Oncology in January 2025. The combination demonstrated promising efficacy and a tolerable safety profile in this setting. At the data cutoff of October 9, 2024, all 20 enrolled previously treated patients were evaluable for efficacy, with a median follow-up duration of 45.7 months. The confirmed ORR was 60.0% and DCR was 85.0%. Median DoR was 13.9 months and median PFS was 15.9 months. Overall survival ("OS") was not reached, and the 36-month OS rate was 58.3%.

On March 18, 2025 Oncorena reported that the FDA has approved the Company’s IND application to initiate the Phase I/II study Oncorella-1: A Phase 1/2, open label, single arm study on safety, tolerability and anti-tumor efficacy of orellanine treatment in patients with metastatic clear-cell or papillary renal cell carcinoma (NCT05287945, ONC001-CL-001) (Press release, Oncorena, MAR 18, 2025, View Source [SID1234651241]).

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In the study Oncorella-1, up to 75 patients with severe metastatic renal cancer requiring dialysis will be enrolled. These patients have exhausted their treatment options and ONC175 represents a potentially new first-in-class treatment for patients with urgent unmet medical need.

The study is currently being conducted at Karolinska University Hospital in Stockholm, Sweden.

Börje Haraldsson, CEO & co-founder of Oncorena comments:

"This approval brings us closer to being able to evaluate the potential for this novel treatment in patients in desperate need for new and better options. We are excited to start the first US site, MD Andersson in Houston, Texas, where the study will be led by investigator Professor Nizar Tannir, a world-leading expert in renal cancer."

About ONC175

ONC175 is an investigational drug product under development that contains synthetically produced orellanine as active ingredient. Orellanine is highly specific to the kidney and induces irreversible renal failure. It is clinically well-known that orellanine does not affect organs other than the kidneys.

In pioneering preclinical studies ONC175 demonstrated a powerful and highly organ-specific mode of action capable of eradicating human metastatic renal cancer cells. The primary goal is to develop ONC175 as a potential curative treatment of metastatic renal cell carcinoma in patients with no remaining kidney function, i.e., patients on dialysis.

About kidney cancer

Approximately 400,000 patients are affected by kidney cancer globally according to the WHO. The disease can often be cured by surgery if detected early, but the prognosis is less favorable if there are metastases. Today, the disease is treated with various types of targeted and immuno-active drugs, that seldom are curative. There is therefore a great and urgent unmet medical need for new, effective and safe drugs.

On March 18, 2025 Medison Pharma , a global company focused on accelerating access to highly innovative therapies in international markets, and Immunocore Holdings plc (NASDAQ: IMCR), a commercial-stage biotechnology company pioneering the delivery of transformative immunomodulatory medicines to radically improve patient outcomes for cancer, infectious diseases and autoimmune diseases, reported that KIMMTRAK (tebentafuspe) has received approval for health registration by the National Health Surveillance Agency (ANVISA), under the regulatory approval pathway for rare diseases (Press release, Medison Pharma, MAR 18, 2025, View Source [SID1234651240]).

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Tebentafuspe is indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mum). This is the first therapy approved by ANVISA for metastatic uveal melanoma in Brazil [1],[2] .
Uveal melanoma is a rare and aggressive eye cancer with limited treatment options available at an advanced stage. Once metastasized, it carries a poor prognosis, and survival rates have remained largely unchanged for decades [ 3] . Developed by Immunocore,
tebentafuspe is an innovative immune mobilization monoclonal T-cell receptor therapy against cancer (ImmTAC) [ 4] designed to engage the body’s immune system to specifically target and destroy uveal melanoma cells.
As part of their long-standing global partnership, Medison and Immunocore are collaborating to bring this therapy to Latin America and beyond the U.S., Japan and Western Europe. Brazil has become the first country in the region to obtain approval for the drug, which offers a new treatment option for patients living with this disease [ 5] .

Mark Moyer , Senior Vice President of Regulatory Sciences at Immunocore said: "Following the approval of the registration, HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in Brazil can now access tebentafuspe. With approvals in 39 countries, this underscores Immunocore’s firm commitment to providing our medicines to patients who can benefit from them around the world."

The approval of tebentafuspe in Brazil underscores Medison’s commitment to expanding access to innovative oncology treatments in Latin America. Victor Papamoniodis , Chief Commercial Officer of Medison Pharma, said: "We are proud of our global partnership with Immunocore that allows us to bring this treatment to Brazilian patients who have not had access to an approved therapy until now. Medison is dedicated to providing the most advanced therapies for rare and serious diseases to patients around the world."

Edson Paixão, General Manager of Medison Pharma in Brazil, Andean Region, Central America and the Caribbean , reinforced: "Medison remains committed to accelerating access to highly innovative therapies for Brazilian patients. The approval of tebentafuspe is an important milestone, and we are proud to make this therapy available to patients who can benefit from it."

About KIMMTRAK (tebentafuspe)

Solution for dilution for infusion with 100 micrograms/0.5 mL in a pack containing 1 vial of 0.5 mL.

INTRAVENOUS USE

ADULT USE

WARNING: Cytokine Release Syndrome (CRS), which can be serious or life-threatening, has occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours after the first three infusions and then as clinically indicated.

Indications: As monotherapy for the treatment of adult patients with unresectable or metastatic uveal melanoma positive for human leukocyte antigen (HLA) A*02:01.

Patients treated with KIMMTRAK must have an HLA-A*02:01 genotype determined by any validated HLA genotyping assay.

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

Warnings and Precautions: Most patients experienced CRS following tebentafuspe infusions. The diagnosis of CRS was most frequently based on pyrexia followed by hypotension and infrequently on hypoxia. Other symptoms commonly observed with CRS included chills, nausea, vomiting, fatigue, and headache. In most cases, CRS began on the day of infusion, with a median time to resolution of 2 days. Pyrexia was observed in nearly all cases of CRS, and in these patients, an increase in body temperature typically occurred within the first 8 hours after tebentafuspe infusion. CRS rarely (1.2%) led to discontinuation of treatment. Patients should be monitored for signs and symptoms of CRS for at least 16 hours after the first three tebentafuspe infusions in a hospital setting with immediate access to resuscitation drugs and equipment to manage CRS. If CRS is observed, immediate supportive care, including antipyretics, intravenous fluids, tocilizumab, or corticosteroids, should be initiated to prevent worsening of the syndrome or potential fatality, and monitoring should continue until resolution. With subsequent doses, patients should be closely monitored after treatment for early identification of signs and symptoms of CRS. Patients with comorbidities, including cardiovascular disorders, may be at increased risk of sequelae associated with CRS. Tebentafuspe treatment has not been studied in patients with clinically significant cardiac disease. Depending on the persistence and severity of CRS, tebentafuspe treatment should be withheld or discontinued. Acute skin reactions with infusion have been reported, including rash, pruritus, erythema, and skin edema. Cardiac events, such as tachycardia and sinus arrhythmia, have been observed in patients on treatment. Cases of QT prolongation have been reported following treatment with tebentafuspe. An electrocardiogram (ECG) should be performed on all patients before and after treatment, during the first 3 weeks and thereafter as clinically indicated. This medicine may potentiate QT interval prolongation, which increases the risk of serious ventricular arrhythmias such as "torsades de pointes", which is potentially fatal (sudden death). This medicine may cause hepatotoxicity. Therefore, it requires careful use, under strict medical supervision and accompanied by periodic controls of liver function, at the physician’s discretion.

Pregnancy and lactation: Women of childbearing potential must use effective contraception during treatment and for at least 1 week after the last dose of treatment. The drug is not recommended during pregnancy and in women of childbearing potential who are not using contraception. Pregnancy in women of childbearing potential should be ascertained before starting treatment. There is insufficient information on the excretion of tebentafuspe/metabolites in human milk. A risk to the newborn/infant cannot be excluded. Breast-feeding should be discontinued during treatment with tebentafuspe.

Drug, food and alcohol interactions: No formal interaction studies have been performed with tebentafuspe. Initiation of tebentafuspe therapy causes a transient release of cytokines that may suppress CYP450 enzymes . The highest risk of drug-drug interactions occurs within the first 24 hours of the first three doses of tebentafuspe in patients who are receiving concomitant CYP450 substrates , particularly those with a narrow therapeutic index. These patients should be monitored for toxicity (e.g., warfarin) or drug concentrations (e.g., cyclosporine). The dose of concomitant medications should be adjusted as necessary.

Dosage: Hospitalization is recommended for at least the first three infusions. The recommended dose is 20 micrograms on Day 1, 30 micrograms on Day 8, 68 micrograms on Day 15, and 68 micrograms once weekly thereafter. Treatment should continue as long as the patient derives clinical benefit and in the absence of unacceptable toxicities. To minimize the risk of hypotension associated with CRS, intravenous fluids should be administered prior to initiating the infusion, based on clinical assessment and the patient’s volume status. Tebentafuspe should be withheld or discontinued to manage adverse reactions. The recommended infusion period is 15 to 20 minutes.

Adverse reactions and laboratory test abnormalities: The most common adverse reactions in patients treated with tebentafusp were CRS (88%), rash (85%), pyrexia (79%), pruritus (72%), fatigue (66%), nausea (56%), chills (55%), abdominal pain (49%), edema (49%), hypo/hyperpigmentation (48%), hypotension (43%), dry skin (35%), headache (32%), and vomiting (34%). Adverse reactions led to permanent discontinuation in 4% of treated patients. The most common adverse reaction resulting in discontinuation of tebentafusp was CRS. Adverse reactions resulting in at least one dose interruption occurred in 26% of treated patients (weekly dosing) and resulted in a median of one missed dose. Adverse reactions requiring dose interruption in ≥2% of patients included fatigue (3%; Grade 1-3), pyrexia (2.7%; Grade 1-3), alanine aminotransferase increased (2.4%; Grade 1-4), aspartate aminotransferase increased (2.4%; Grade 1-3), abdominal pain (2.1%; Grade 1-3), and lipase increased (2.1%; Grade 1-3). Adverse reactions leading to dose modification in ≥1% of patients were CRS (1.9%; Grade 1-3) and hypotension (1.1%; Grade 2-4). Very common adverse reactions were: CRS, decreased appetite, hypomagnesemia, hyponatremia, hypocalcemia, hypokalemia, insomnia, headache, dizziness, paresthesia, tachycardia, hypotension, flushing, hypertension, cough, dyspnea, nausea, vomiting, diarrhea, abdominal pain, constipation, dyspepsia, rash, pruritus, dry skin, hypo/hyperpigmentation, erythema, arthralgia, back pain, myalgia, pain in extremity, pyrexia, fatigue, chills, edema, influenza-like illness, increased aspartate aminotransferase, increased alanine aminotransferase, increased serum bilirubin, increased lipase, anemia, decreased lymphocyte count, decreased serum phosphate, increased serum creatinine. See other adverse reactions in the full product leaflet.

Registration: 1.9132.0001/ Medison Pharma Brasil Produtos Farmacêuticos LTDA /CNPJ 48.682.588/0001-37/ Rua Nelson Pontes , 125 Bloco 5 e 6. Jardim Margarida. Vargem Grande Paulista/SP/Indústria Brasileira/ KIMMTRAK/SAC: 0800-633-4766. SALE UNDER PRESCRIPTION. USE RESTRICTED TO HEALTHCARE ESTABLISHMENTS. If symptoms persist, a physician should be consulted. Scientific documentation and additional information are available from Customer Service and the service department for prescribers and dispensers of medication. Product information approved by Anvisa is available at View Source

On March 18, 2025 Hoth Therapeutics, Inc. (NASDAQ: HOTH), a clinical-stage biopharmaceutical company, reported breakthrough preclinical findings demonstrating the efficacy of HT-KIT, a novel targeted therapy for gastrointestinal stromal tumors (GIST) (Press release, Hoth Therapeutics, MAR 18, 2025, View Source [SID1234651239]). The results highlight HT-KIT’s ability to significantly reduce tumor burden in humanized mouse models, disrupt KIT signaling pathways, and induce tumor cell death.

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"These exciting findings mark a significant milestone in the development of HT-KIT as a potential new therapeutic for patients with GIST," said Robb Knie, CEO of Hoth Therapeutics.

"By targeting KIT mutations, which are a major driver of GIST progression, HT-KIT has shown remarkable efficacy in preclinical models, demonstrating its potential as a transformative treatment option for this difficult-to-treat cancer."

Key Findings from the Preclinical Study:

Significant Reduction in KIT Expression – HT-KIT effectively reduced KIT receptor expression within 24 hours, with effects sustained for 72 hours.
Induction of Tumor Cell Death – HT-KIT triggered significant tumor cell death as early as 24 hours post-treatment, while the lower dose led to delayed but substantial cell death at 72 hours.
Decreased Tumor Cell Proliferation – HT-KIT treatment inhibited cell growth and proliferation in GIST-T1 cells, as confirmed by cell count reductions and decreased fluorescence intensity in proliferation assays.
Marked Tumor Volume Reduction in GIST Mouse Models – In a humanized xenograft model, HT-KIT treatment led to a significant reduction in tumor growth, with differences becoming statistically significant by day 8 and increasing over time.
Consistent Tumor Size Reduction – Excised tumors from HT-KIT-treated mice were smaller and lighter than those in the control group, reinforcing tumor volume measurements.
HT-KIT: A Potential New Treatment for GIST

GIST is a rare but aggressive cancer often driven by activating mutations in the KIT receptor. Current treatment options, including tyrosine kinase inhibitors (TKIs), can face resistance over time, leading to disease progression. Hoth Therapeutics’ HT-KIT offers a novel approach by effectively reducing KIT receptor expression, disrupting tumor survival pathways, and inhibiting tumor growth in vivo.

"These results provide compelling preclinical proof-of-concept for HT-KIT in GIST treatment," said Robb Knie. "By directly targeting the underlying genetic drivers of GIST, HT-KIT has the potential to overcome limitations of existing therapies and provide a new therapeutic strategy for patients with KIT-driven malignancies."

Next Steps in Development

Hoth Therapeutics is committed to advancing HT-KIT toward clinical evaluation. The company is currently conducting additional preclinical studies to further validate HT-KIT’s efficacy and safety profile, with plans to initiate regulatory discussions for first-in-human trials.