Tivdak (tisotumab vedotin-tftv) / Genmab, ZAI Lab, Pfizer - LARVOL DELTA

Epidemiology of tissue factor expression in soft tissue sarcoma (AACR 2025) - "Doxorubicin-based chemotherapy, the standard treatment for the majority of advanced or metastatic STS, has limited efficacy, with low response rates and poor disease control...Consequently, a TF-targeted antibody-drug conjugate (tisotumab vedotin) has been approved by the Food and Drug Administration for the treatment of cervical cancer.As its expression in STS remains unexplored, we aimed to assess the expression of TF in tissue microarrays (TMA) constructed from archival tumor material from patients and patient-derived xenograft (PDX) models... TF expression in STS is generally limited, with MFS showing the highest number of positivity in clinical samples and xenograft models. Nevertheless, the observed frequency appears insufficient to support TF as suggestive therapeutic target across other subtypes of sarcomas."

Clinical • Angiosarcoma • Cervical Cancer • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

ADCE-T02: A first-in-class topoisomerase-1 inhibitor based antibody drug conjugate against tissue factor demonstrates excellent preclinical efficacy and tolerability (AACR 2025) - P1 | "The TF-ADC tisotumab-vedotin (Tivdak®) has been approved for treatment of cervical cancer but is associated with serious side effects including ocular toxicities, peripheral neuropathy, and bleeding.ADCE-T02 is a first-in-class Topoisomerase-1 inhibitor TF-ADC composed of a humanized anti-TF IgG1 monoclonal antibody (Ab-754), conjugated via a novel T1000 linker moiety to the Topoisomerase-1 inhibitor Exatecan payload at a drug-to-antibody ratio (DAR) of 4.ADCE-T02 binds with high affinity to human recombinant TF protein and multiple TF positive cell lines. In vivo, ADCE-T02 shows strong anti-tumor activity in a wide range of solid tumor models including pancreatic cancer, esophageal squamous cell carcinoma, NSCLC and HNSCC and is well tolerated in non-human primate toxicology studies with no evidence of ocular toxicity, peripheral neuropathy, or bleeding.In summary, ADCE-T02 constitutes a novel first-in-class Topoisomerase-1 inhibitor ADC targeting TF with a..."

Preclinical • Cervical Cancer • Colorectal Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Molecular profiling of tisotumab vedotin-treated patients identified immune pathways associated with clinical activity, supporting the multimodal mechanism of action (AACR 2025) - "Immune gene signatures associated with the Fc-mediated effector mechanisms of antibody-dependent cellular cytotoxicity (NK cells) and antibody-dependent cellular phagocytosis (macrophages/monocytes) were associated with improved OS and overall response rate in innovaTV204 patients. Preclinical results demonstrate Fc-dependent immune cell engagement as a MoA of TV. Together, these results provide additional evidence of TV's multimodal MoA in patients with advanced cervical cancer."

Clinical • Cervical Cancer • Oncology • Solid Tumor

Development of an anti-TF ADC with a potentially improved therapeutic index (AACR 2025) - "Significantly, while Tisotumab displayed significant disruption of TF/factor VII interaction, a potential cause for excessive bleeding observed in clinics using Tisotumab Vedotin, 1E11 showed little or no such activities. These highly relevant function and safety features of 1E11-based ADC plus its excellent developability profile suggest that it is a promising candidate for further development into various ADC based therapeutics either used alone or in combination with other therapeutics."

Cervical Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor

PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs; approval of amivantamab plus lazertinib for non-small cell lung cancer, durvalumab for small cell lung cancer, tislelizumab for esophageal cancer, tisotumab vedotin for cervical cancer, ivosidenib for leukemia, and venetoclax for lymphoma in Japan. (PubMed, Int J Clin Oncol) - No abstract available

Japanese regulatory • Journal • Cervical Cancer • Esophageal Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

The efficacy and safety of Tisotumab Vedotin in the treatment of recurrent/metastatic cervical cancer: a systematic review and meta-analysis of single-arm studies (Frontiers) - "A total of 5 articles (covering 7 studies and 527 patients) were included in this study. The meta-analysis results revealed that the median OS, median PFS, ORR, and DCR were 11.83 months, 4.22 months, 29.9%, and 75.1%, respectively, for patients treated with TV. The incidence of AEs was 99.1%, and AEs at Grades 3-5 were reported in 61.7% of patients."

Retrospective data • Cervical Cancer

Rapidly progressive pneumonitis days after receiving tisotumab vedotin: a new antibody-drug conjugate. (PubMed, BMJ Case Rep) - "The patient was treated with high-dose intravenous steroids and immunoglobulin, leading to eventual recovery. This case exhibits the potential for severe pulmonary toxicity associated with TV and highlights the need for greater awareness and investigation of adverse effects related to ADCs."

Journal • Cervical Cancer • Infectious Disease • Inflammation • Oncology • Pneumonia • Solid Tumor • Squamous Cell Carcinoma

A Review of NICE UK Submissions for Antibody-Drug Conjugates in Oncology (ISPOR 2025) - "All of these ADCs were assessed by NICE from inception to 2024 12 FDA-approved ADCs were identified: Trastuzumab emtansine, Trastuzumab deruxtecan, Sacituzumab govitecan, Inotuzumab ozogamicin, Polatuzumab vedotin, Loncastuximab tesirine, Tisotumab vedotin, Enfortumab vedotin, Mirvetuximab soravtansine-gynx, Belantamab mafodotin-blmf, Gemtuzumab ozogamicin, and Brentuximab vedotin. In conclusion, ADCs have revolutionized cancer treatment with their targeted delivery and significant therapeutic benefits. The evolution of ADCs since 2000 highlights their potential in both refractory and early-stage diseases. Continued advancements in ADC design and technology promise even greater therapeutic efficacy."

NICE • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Cell Lymphoma • Breast Cancer • Cervical Cancer • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer

TIVDAK (tisotumab vedotin) Approved by European Commission for Previously Treated Recurrent or Metastatic Cervical Cancer (Genmab Press Release) - "Genmab A/S...announced today that the European Commission (EC) has granted marketing authorization for TIVDAK (tisotumab vedotin), an antibody-drug conjugate (ADC), as monotherapy treatment for adult patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy. TIVDAK is the first and only ADC to be granted European Union (EU) marketing authorization for people living with recurrent or metastatic cervical cancer....The approval is supported by data from the global, randomized, Phase 3 innovaTV 301 trial (NCT04697628) that evaluated the efficacy and safety of TIVDAK compared to chemotherapy in patients with advanced or recurrent cervical cancer who were previously treated with chemotherapy."

EMA approval • Cervical Cancer

TIVDAK (tisotumab vedotin) Approved by Japan Ministry of Health, Labour and Welfare for the Treatment of Advanced or Recurrent Cervical Cancer that has Progressed on or after Chemotherapy (GlobeNewswire) - "Genmab A/S...today announced that the Japan Ministry of Health, Labour and Welfare has approved TIVDAK (tisotumab vedotin) for the treatment of advanced or recurrent cervical cancer that has progressed on or after cancer chemotherapy. TIVDAK is the first and only ADC to be approved for people living with cervical cancer in Japan....The approval is based on data from the randomized, open-label, global Phase 3 innovaTV 301 clinical trial that evaluated the efficacy and safety of TIVDAK compared to chemotherapy in patients with advanced or recurrent cervical cancer who were previously treated with chemotherapy."

Japan approval • Cervical Cancer

Clinical applications of antibody drug conjugates for gynecologic malignancies: Review of available medicines and emerging therapeutics. (PubMed, Gynecol Oncol) - "For patients with FIGO stage III-IVA locally advanced cervical cancer, irrespective of PD-L1 status, chemoradiation plus pembrolizumab followed by maintenance pembrolizumab also confers a survival benefit. For newly diagnosed advanced ovarian cancer responding to primary systemic chemotherapy, maintenance therapy using PARP inhibitors and/or bevacizumab according to germline and somatic mutational analysis have been demonstrated to improve progression-free survival...Adverse event mitigation strategies, biomarker discovery, and sequencing are paramount in successfully exploiting the therapeutic window provided by these novel compounds. This review discusses the application of ADCs in gynecologic cancers, including the current FDA-approved drugs mirvetuximab soravtansine, tisotumab vedotin, and trastuzumab deruxtecan, as well as relevant ongoing clinical trials, including TROP2 ADCs."

Clinical • IO biomarker • Journal • Review • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • PD-L1

Zai Lab Announces Fourth Quarter and Full Year 2024 Financial Results and Recent Corporate Updates (Businesswire) - "Tisotumab Vedotin (Tissue Factor ADC): BLA submission in recurrent or metastatic cervical cancer following progression on or after chemotherapy in the first quarter of 2025. Bemarituzumab (FGFR2b): BLA submission in first-line gastric cancer in the first half of 2025. Repotrectinib (ROS1/TRK): supplementary NDA submission in NTRK+ solid tumors in the first half of 2025. Tumor Treating Fields (TTFields): Marketing Authorization Application submissions in second-line+ NSCLC following progression on or after platinum-based chemotherapy and in first-line pancreatic cancer...Second-Line+ Extensive-Stage SCLC (ES-SCLC): Zai Lab to present updated data at a major medical conference in the first half of 2025. Zai Lab plans to initiate a pivotal study in 2025...Other neuroendocrine tumors: Zai Lab to initiate a global Phase 1 study in the first half of 2025...ZL-6201 (LRRC15 ADC): Zai Lab to provide preclinical data update and initiate a global Phase 1 study in sarcoma."

China filing • Clinical data • New P1 trial • Preclinical • Cervical Cancer • Gastric Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor

Second-line antibody-drug conjugates for the treatment of metastatic human papillomavirus-independent gastric-type adenocarcinoma of cervix: The Singapore experience. (PubMed, Gynecol Oncol Rep) - "The antibody-drug conjugates (ADCs) tisotumab vedotin-tftv (TV) and trastuzumab deruxtecan (T-DXd) are approved for use in previously treated metastatic cervical cancer, the latter in HER2-expressing tumors. There is paucity of data regarding the efficacy and safety of TV and T-DXd in the management of metastatic GAS. We report outcomes of four patients with metastatic GAS who were treated with these ADCs in the second-line setting in Singapore."

Journal • Cervical Adenocarcinoma • Cervical Cancer • Gastric Cancer • Mucinous carcinoma • Oncology • Solid Tumor • HER-2

F3 Expression Drives Sensitivity to the Antibody-Drug Conjugate Tisotumab Vedotin in Glioblastoma. (PubMed, Cancers (Basel)) - "TisVed targets high-TF-expressing IDHwt GBM, but not low-TF-expressing IDHmut glioma. This is predominately through the vedotin conjugate rather than inhibition of TF signaling. Though the effect size is modest, TisVed shows anticancer effects against IDHwt GBM. However, there could be complications related to hemostasis and hemorrhage."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Hematological Disorders • Oncology • Solid Tumor • IDH1 • IDH2

Zai Lab Announces Acceptance of Biologics License Application for TIVDAK for the Treatment of Patients with Recurrent or Metastatic Cervical Cancer (Businesswire) - "Zai Lab Limited...announced that China’s National Medical Products Administration (NMPA) has accepted the Biologics License Application (BLA) for TIVDAK (tisotumab vedotin-tftv) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy....The BLA submission is supported by the results from the global, randomized, Phase 3 innovaTV 301 clinical trial (NCT04697628) and the results from the China subpopulation of this study."

China filing • Cervical Cancer

innovaTV 301: Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer (clinicaltrials.gov) - P3 | N=502 | Active, not recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Aug 2025 ➔ May 2026

Trial completion date • Cervical Cancer • Oncology • Solid Tumor

Tisotumab vedotin: “The committee was reminded of the status of this application and its remaining outstanding issues. The CHMP agreed to the request by the applicant for an extension to the clock stop to respond to the list of outstanding issues adopted in October 2024.The Committee adopted a list of outstanding issues with a specific timetable”; Metastatic cervical cancer (European Medicines Agency) - CHMP Final Minutes of the meeting on 14- 17 Oct 2024

CHMP • Cervical Cancer • Oncology

KEYNOTE-E02: Efficacy and Safety Study of Tisotumab Vedotin for Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=352 | Active, not recruiting | Sponsor: Seagen Inc. | Trial completion date: Nov 2026 ➔ Aug 2026 | Trial primary completion date: Feb 2026 ➔ Sep 2025

Trial completion date • Trial primary completion date • Colorectal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

F3 Expression Drives Sensitivity to the Antibody-Drug Conjugate Tisotumab Vedotin in Glioblastoma (Multidisciplinary Digital Publishing Institute) - "TisVed was more active against cultured IDHwt GBM cells than IDHmut glioma cells. This activity was increased by the daily washout of soluble TF secreted by IDHwt GBM cells. Unconjugated Tis had less effect than TisVed, and TF signaling was minimally inhibited. TisVed extended the survival of mice intracranially engrafted with IDHwt GBM (p = 0.006), but not mice with IDHmut glioma (p = 0.88). TisVed also reduced the growth of IDHwt GBM flank xenografts."

Preclinical • Glioblastoma

Practical clinical management of ocular adverse events related to Antibody-Drug Conjugates in gynaecological malignancies. (PubMed, Cancer Treat Rev) - "Clinicians ought to be cognizant of the potential ocular toxicity of ADCs. Proactive prophylaxis, patient education and a multidisciplinary approach involving ophthalmologists are paramount to minimising the impact of these AEs. Further research is essential to measure the real outcome of preventive strategies and balance their benefits with potential short and long-term risks."

Adverse events • Journal • Review • Conjunctivitis • Gynecologic Cancers • Ocular Infections • Ocular Inflammation • Oncology • Ophthalmology • Pain

TroFuse-020/GOG-3101/ENGOT-Cx20: A Phase 3, Randomised, Active-Controlled, Open-Label, Multicentre Study Comparing Sacituzumab Tirumotecan Monotherapy Vs Treatment Of Physician's Choice As Second-Line Treatment For Recurrent Or Metastatic Cervical Cancer (ESGO 2025) - P3 | "This phase 3, randomised, open-label, multicentre study (NCT06459180) evaluates the efficacy and safety of sac-TMT monotherapy vs treatment of physician's choice (TPC) as second-line treatment in patients with recurrent/metastatic cervical cancer.Methodology Eligible patients are aged ≥18 years with progressive recurrent/metastatic cervical cancer, measurable per Response Evaluation Criteria in Solid Tumours version 1.1 by the investigator, and had received 1 prior line of platinum doublet chemotherapy (±bevacizumab) and anti‒programmed cell death protein 1/anti‒programmed cell death ligand 1 therapy as a part of cervical cancer regimens...~666 patients will be randomly assigned 1:1 to receive either sac-TMT 4 mg/kg intravenously (IV) every 2 weeks (Q2W) or TPC (pemetrexed 500 mg/m2 IV Q3W; tisotumab vedotin 2 mg/kg IV Q3W; topotecan 1 or 1.25 mg/m2 on days 1–5 of each 3-week treatment cycle; vinorelbine 30 mg/m2 on days 1 and 8 of each 3-week treatment..."

Clinical • Metastases • Monotherapy • P3 data • Cervical Cancer • Oncology • Solid Tumor

KEYNOTE-834: Safety and Efficacy of Tisotumab Vedotin Monotherapy & in Combination With Other Cancer Agents in Subjects With Cervical Cancer (clinicaltrials.gov) - P1/2 | N=214 | Active, not recruiting | Sponsor: Seagen Inc. | Trial completion date: Dec 2024 ➔ Mar 2026 | Trial primary completion date: Dec 2024 ➔ Mar 2026

Monotherapy • Trial completion date • Trial primary completion date • Cervical Cancer • Oncology • Solid Tumor

Updates on Latest Clinical Trials that Have Changed Our Disease Management (ESGO 2025) - "Key updates from recent clinical trials include the use of PARP inhibitors (olaparib, niraparib, rucaparib) for advanced epithelial ovarian cancer, especially in patients with BRCA mutations or HRD...Antibody-Drug Conjugates (ADCs) beyond mirvetuximab soravtansine are also under investigation for ovarian cancer.In endometrial cancer, adding ICIs (e.g., dostarlimab, pembrolizumab) to chemotherapy has significantly improved progression-free survival, with positive overall survival data from the RUBY trial. Trials for MMR-proficient endometrial cancer are ongoing, exploring ADCs.For advanced or recurrent cervical cancer, the KEYNOTE-826 trial demonstrated improved overall survival with pembrolizumab plus chemotherapy (± bevacizumab), establishing pembrolizumab as a standard treatment. Tisotumab vedotin, an ADC-targeting tissue factor, has shown benefit in recurrent cervical cancer after standard treatments. Other ADCs are currently investigated in the recurrent..."

Clinical • IO biomarker • Cervical Cancer • Endometrial Cancer • Epithelial Ovarian Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • BRCA

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 27-30 January 2025 (European Medicines Agency) - "On 30 January 2025, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Tivdak, intended for the treatment of recurrent or metastatic cervical cancer. The applicant for this medicinal product is Pfizer Europe MA EEIG. Tivdak will be available as a 40 mg powder for concentrate for solution for infusion....Tivdak as monotherapy is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy."

CHMP • Cervical Cancer

Ocular surface disease related to tisotumab vedotin-tftv. (PubMed, Gynecol Oncol Rep) - "Oncologists and ophthalmologists should be aware of the possibility of these ocular complications, especially as more ADCs are approved. Further studies are required to determine toxicity mechanisms as well as optimal prophylaxis and management strategies."

Journal • Cervical Cancer • Conjunctivitis • Fibrosis • Immunology • Keratitis • Ocular Infections • Ocular Inflammation • Oncology • Ophthalmology • Solid Tumor • Transplantation