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

Trial in progress update on ENGOT-cx8/GOG-3024/innovaTV 205: Addition of a new cohort with first-line (1L) tisotumab vedotin (TV) + pembrolizumab (pembro) + carboplatin (carbo) ± bevacizumab (bev) in recurrent/metastatic cervical cancer (r/mCC). (ASCO 2022) - P1b/2 | "The primary endpoint of this dose expansion phase is confirmed ORR per RECIST v1.1; secondary endpoints include DOR, time to response, progression-free survival, OS, and safety. Enrollment is ongoing in the United States and Europe, with additional sites planned globally."

Clinical • Cervical Cancer • Oncology • Solid Tumor • PD-L1

innovaTV 301/ENGOT-cx12/GOG-3057: A global, randomized, open-label, phase III study of tisotumab vedotin vs investigator's choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer (ESMO 2023) - P3 | "Pts were randomized 1:1 to TV monotherapy or investigator's choice of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed...63.9% and 27.5% of pts had prior bevacizumab and prior anti-PD-(L)1 therapy, respectively...AEs were consistent with the known TV safety profile, including for ocular, peripheral neuropathy, and bleeding AEs. Conclusions In the phase 3 innovaTV 301 study, TV showed a statistically significant and clinically meaningful improvement in OS, PFS, and ORR vs chemotherapy, with a manageable and tolerable safety profile in pts with 2L/3L r/mCC."

Clinical • Late-breaking abstract • Metastases • P3 data • Cervical Cancer • Oncology • Solid Tumor

Tissue factor-targeted antibody-drug conjugates in cervical cancer: Focus on tisotumab vedotin. (PubMed, Cancer Treat Res Commun) - "In this review I examine the biological rationale for the use of TV, the design of TV and its clinical use, the clinical evidence for its use, as well as how toxicity is managed with treatment with TV, and I discuss unresolved issues surrounding TV, specifically as they pertain to the very limited clinical data that have been published regarding resistance mechanisms for the TV treatment modality. I also discuss the important need for the development of predictive biomarkers for TV and the development of rational combinations with other agents for use in combination with TV."

Journal • Review • Cervical Cancer • Oncology • Solid Tumor

Patient-reported outcomes with tisotumab vedotin versus chemotherapy in patients with recurrent or metastatic cervical cancer: post hoc analyses from the open-label, randomized, phase 3 ENGOT-cx12/GOG-3057/innovaTV 301 trial. (PubMed, Int J Gynecol Cancer) - P3 | "Results suggest tisotumab vedotin maintained health-related quality of life in patients with previously treated recurrent or metastatic cervical cancer and, together with clinical outcomes with innovaTV 301, support tisotumab vedotin as a treatment option in this setting."

Journal • P3 data • Retrospective data • Cervical Cancer • CNS Disorders • Insomnia • Oncology • Pain • Pulmonary Disease • Sleep Disorder • Solid Tumor

Tisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer. (PubMed, N Engl J Med) - P3 | "In patients with recurrent cervical cancer, second- or third-line treatment with tisotumab vedotin resulted in significantly greater efficacy than chemotherapy. (Funded by Genmab and Seagen [acquired by Pfizer]; innovaTV 301 ClinicalTrials.gov number, NCT04697628.)."

Clinical • Journal • Cervical Cancer • Oncology • Solid Tumor

Targeted Anti-TF Antibody-Drug Conjugates in Advanced Cervical Cancer-Tisotumab Vedotin-Systematic Review. (PubMed, Cancers (Basel)) - "It also has the potential for use in first-line multi-drug treatment regimens. Strict adherence to safety protocols is essential to minimise toxicity and ensure treatment continuity."

Journal • Review • Cervical Cancer • Hematological Disorders • Oncology • Ophthalmology • Pain • Solid Tumor

Establishment of an Onco-Ophthalmology Collaboration for Tisotumab Vedotin and Initial Experience with Ocular Adverse Events (PubMed, Gan To Kagaku Ryoho) - "Whilst preventative measures are crucial, ocular complications remain possible. This case demonstrates that early diagnosis and effective management are achievable through the onco-ophthalmology liaison system, ensuring the safe continuation of TV therapy."

Adverse events • Journal • Cervical Cancer • Conjunctivitis • Ocular Infections • Ocular Inflammation • Oncology • Ophthalmology • Solid Tumor

Antibody drug conjugates in gynaecological cancers: navigating between opportunities and challenges. (PubMed, EClinicalMedicine) - "Currently, three ADCs are clinically available for the treatment of gynaecological cancers: Mirvetuximab soravtansine for FRα-positive ovarian cancer, Tisotumab vedotin (targeting TF) for cervical cancer, and Trastuzumab deruxtecan for HER2-positive solid tumors. Upon positive results from phase III trials, new treatment options will be available to reshape the standard of care of gynaecological malignancies and improve patients' outcome. This review summarizes the major clinical studies of ADCs in ovarian, endometrial and cervical cancer, and explores the main challenges related to their use in clinical practice."

Journal • Review • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • CD276 • CDH6 • CLDN6 • FOLR1 • HER-2 • SLC34A2 • VTCN1

Multi-target-directed drugs: new additions in 2025 and post-marketing safety surveillance of drugs marketed in 2022-2024. (PubMed, Pharmacol Rep) - "Most of them are antibody-drug conjugates, bispecific antibodies, or kinase inhibitors, all of which are indicated for tumor treatment, including datopotamab deruxtecan (hormone receptor-positive, HER2-negative breast cancer), tisotumab vedotin (advanced cervical carcinoma), linvoseltamab (fourth-line treatment of multiple myeloma), and erdafitinib (advanced urothelial carcinoma). New safety signals have been identified, including Stevens-Johnson syndrome and progressive multifocal leukoencephalopathy. The analysis also revealed a more favorable safety profile of the MTDL tirzepatide (a dual glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide analogue) compared to the single-targeted drug semaglutide (glucagon-like peptide-1 analogue), including lower reporting rates of acute kidney injury and no significant suicidality signal."

Journal • P4 data • Review • Acute Kidney Injury • Breast Cancer • Cervical Cancer • CNS Disorders • Hematological Malignancies • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Multiple Myeloma • Nephrology • Oncology • Rare Diseases • Renal Disease • Solid Tumor • Steven-Johnson Syndrome • Urothelial Cancer • HER-2

Molecular Profiling of Tisotumab Vedotin-Treated Patients Identifies Immune Pathways Associated With Clinical Activity. (PubMed, Clin Cancer Res) - P2 | "This work provides supportive evidence for TV mechanisms of action that involve antitumor effects through direct cytotoxic and immune effector-mediated mechanisms. The association of immune-related gene signatures with improved clinical outcomes supports a multimodal mechanism of action for TV in the clinic and provides further rationale for antibody-drug conjugate efficacy in tumors with heterogeneous target expression."

Journal • Cervical Cancer • Oncology • Solid Tumor

Preclinical activity of tisotumab vedotin, an antibody-drug conjugate targeting tissue factor, in uterine serous carcinoma. (PubMed, Gynecol Oncol) - "TF was detected in more than half of evaluable USC specimens. TV exhibits potent preclinical anti-tumor activity in TF-expressing USC cell lines and xenografts. Clinical investigations of TV in USC patients with TF expression are warranted."

Journal • Preclinical • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Oncology • Solid Tumor • Uterine Cancer

Tissue Factor-High Ovarian Clear Cell Carcinoma Shows Immune-Cold Features and Preclinical Activity of Tisotumab Vedotin. (PubMed, Cancer Sci) - "In patient-derived models, higher TF expression was associated with greater sensitivity to tisotumab vedotin (TV) in vitro, and TV treatment significantly suppressed xenograft growth in vivo. These findings support TF-high OCCC as an immune-cold subgroup characterized by proliferative transcriptional programs, frequent B7-H4 co-expression, and preclinical sensitivity to TV."

Journal • Preclinical • Clear Cell Carcinoma • Oncology • Ovarian Cancer • VTCN1

Antibody-drug conjugates in selected solid tumours: a position statement update based on findings from the third workshop held by the ETOP IBCSG Partners Foundation. (PubMed, ESMO Open) - "Recent positive phase III trial data have further incorporated ADCs into the standard of care [e.g. lung: sacituzumab tirumotecan; breast: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan, datopotamab deruxtecan; muscle-invasive bladder cancer: enfortumab vedotin; ovarian cancer: mirvetuximab soravastine; cervical cancer: tisotumab vedotin]...Importantly, although several ADCs have been successfully developed without mandatory biomarker selection, biomarker-driven ADC development enables rational patient selection, as illustrated by multiple ADCs (e.g. T-DXd, mirvetuximab soravtansine and telisotuzumab vedotin)...Additional ADC research priorities include the optimisation of ADC constructs to enhance efficacy/tolerability and the identification of reliable ADC targets, including work to elucidate attributes of already-identified targets. Finally, considering the vast amount of ADC-related data being generated, artificial intelligence could be leveraged to analyse..."

Journal • Review • Bladder Cancer • Breast Cancer • Cervical Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Solid Tumor

Development, Validation, and Application of an LC-MS/MS Method for Pharmacokinetic Studies for the Datopotamab Deruxtecan-Dlnk Quantification in Rat Plasma. (PubMed, Biomed Chromatogr) - "The internal standard was tisotumab vedotin. After intravenous injection, the validated approach was effectively applied to pharmacokinetic research in rats, allowing for accurate estimates of important pharmacokinetic parameters. This approach is ideal for routine bioanalysis and pharmacokinetic evaluation of datopotamab deruxtecan-dlnk in preclinical research."

Journal • PK/PD data • Preclinical

Diverse Conjunctival Adverse Events Associated with Tisotumab Vedotin. (PubMed, Ophthalmology) - No abstract available

Adverse events • Journal

The WEE1 inhibitor azenosertib broadly enhances efficacy of antibody-drug conjugates with topoisomerase I and microtubule inhibitor payloads. (PubMed, iScience) - "Azenosertib enhanced the activity of free TOP1i agents and TOP1i-based ADCs (trastuzumab deruxtecan [T-DXd] and sacituzumab govitecan), increasing DNA damage and apoptosis, and extended the duration of response while overcoming T-DXd resistance in patient-derived xenografts. Synergistic effects were also observed with MTI agents and MTI-based ADCs (mirvetuximab soravtansine, tisotumab vedotin, and enfortumab vedotin), associated with exacerbated mitotic defects and prolonged mitotic arrest. All combinations enhanced efficacy and were well tolerated in vivo. These findings position azenosertib as a broadly applicable enhancer of cytotoxic-payload ADCs, offering a promising strategy for patients with advanced solid tumors."

Journal • Oncology • Solid Tumor • TOP1

Tisotumab Vedotin in Squamous Cell Carcinoma of the Vulva (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: GOG Foundation

New P2 trial • Gynecologic Cancers • Oncology • Solid Tumor • Squamous Cell Carcinoma • Vulvar Cancer

Recurrent cervical carcinoma in the era of antibody-drug conjugates (ADCs): Is sustained, durable remission achievable? (WAGO 2026) - "Objectives Median overall survival for first-line treatment of recurrent/metastatic cervical carcinoma has steadily increased over the past 15 years from 6m (single-agent platinum) to 12m (platinum-based chemoRx doublet) to 17m (chemoRx + bevacizumab) and, for tumors that express PD-L1, to 24m (chemoRx + pembrolizumab ± bevacizumab)...Second-line therapies employing ADCs like tisotumab vedotin (TV) or trastuzumab-deruxtecan (T-DXd for HER2-expressers) demonstrate objective response rates 17.8% (TV) & 50% (T-DXd) and durations of response 5.7m (TV) & 14.2m (T-Dxd)...Referred to academic center and enrolled on GOG-3024/innovate-205 receiving TV (2mg/kg) + carboplatin (AUC5)...Conclusions To our knowledge this is the first report of a >5-year survivor without evidence of disease following 3rd- line treatment for recurrent SCCA cervix, far exceeding reported clinical benefit in this setting (Table 1) and demonstrating possible durable remission with ADCs in..."

ADC • Clinical • IO biomarker • Cervical Cancer • Cervical Squamous Cell Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • HER-2 • NTRK • PD-L1

Antibody–Drug Conjugates in Gynecologic Cancer Patients with Brain Metastases (WAGO 2026) - "Time to median CNS- PFS survival probability with mirvetuximab soravtansine (MIRV) was 5.5 months (95% CI, 1.8–NA) in 4 of 6 patients, 6.8 months (NA) in 1 of 2 trastuzumab deruxtecan (T-DXd)-treated patients, and 9.3 months (NA) in the single patient treated with tisotumab vedotin (TV). These findings should be interpreted with caution given the limited cohort size. Ongoing accrual of patients treated with ADCs and BM, including those with active CNS disease, is essential to better define CNS efficacy and inform inclusion of this historically understudied population in future trials."

ADC • Clinical • Gynecologic Cancers • Oncology • Solid Tumor

Ocular Toxicity in Patients Receiving Antibody–Drug Conjugates for Gynecologic Malignancies in a high-altitude environment (WAGO 2026) - "Majority of patients were on mirvetuximab (n-83, 69.2%), followed by trastuzumab deruxtecan (n=20,16.7%) and tisotumab vedotin (n=18, 15%). The observed association between ocular toxicity and improved survival may be related to improved treatment effect. While dry eye is common in high-altitude environments, it is reassuring that altitude-related hypoxia and ocular surface stress does not seem to contribute significantly to ocular toxicity in this population."

ADC • Clinical • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Peritoneal Cancer

Real-world pharmacovigilance analysis for antibody drug conjugates (ADCs) in treatment of solid tumor malignancies. (ASCO 2026) - " We conducted a disproportionality analysis of FDA Adverse Event Reporting System (FAERS) pharmacovigilance data (Q1 2021–Q1 2024) for six FDA-approved ADCs: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), enfortumab vedotin (EV), mirvetuximab soravtansine (MIRV), tisotumab vedotin (TV), and trastuzumab emtansine (T-DM1). ADC toxicity is not class-wide but is instead affected by payload, linker, and target. TOPO1 inhibitor ADCs showed divergent toxicity profiles despite payloads, while MMAE ADCs have toxicities related to target expression in normal tissues. Maytansinoid ADC toxicities were distinct, reflecting both payload-dependent effects (DM4 vs DM1) and target-dependent effects (T-DM1)."

ADC • Adverse events • Clinical • Real-world • Real-world evidence • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Infectious Disease • Interstitial Lung Disease • Neutropenia • Oncology • Pneumonia • Portal Hypertension • Pulmonary Disease • Respiratory Diseases • Septic Shock • Solid Tumor

Comparison of cardiovascular outcomes among solid tumor ADCs: A tumor-agnostic observational study. (ASCO 2026) - " We utilized data from the Global Collaborative Network-TriNetX to assess cardiovascular outcomes associated with seven ADCs: trastuzumab deruxtecan, sacituzumab govitecan, enfortumab vedotin, ado-trastuzumab emtansine, tisotumab vedotin, mirvetuximab soravtansine, and datopotamab deruxtecan. Our study demonstrates significant variability in cardiovascular toxicity among ADCs. Ado-trastuzumab emtansine, enfortumab vedotin, and sacituzumab govitecan showed the highest cardiomyopathy and heart failure rates, while trastuzumab deruxtecan demonstrated a favorable profile. These findings highlight the importance of cardiovascular risk stratification and monitoring in patients receiving ADC therapy."

ADC • Clinical • Observational data • Pan tumor • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Oncology • Solid Tumor

Antibody-drug conjugates in gynaecological cancers: opportunities and challenges. (PubMed, Nat Rev Clin Oncol) - "Three ADCs are currently approved for previously treated gynaecological cancers: mirvetuximab soravtansine for folate receptor-α-positive ovarian cancer, trastuzumab deruxtecan for solid tumours expressing HER2 (defined as a staining intensity on immunohistochemistry of 3+) and tisotumab vedotin for cervical cancer (independent of tissue factor expression). Moreover, rational combinations could reinforce and extend the clinical potential of these agents, as has already been demonstrated with the addition of ADCs to immune checkpoint inhibitors in an effort to amplify antitumour immunity and prolong the durability of clinical responses. In this Review, we provide an overview of the current landscape of ADCs in gynaecological malignancies, highlighting key advances and future opportunities."

IO biomarker • Journal • Review • Cervical Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • FOLR1 • HER-2

Tisotumab vedotin versus chemotherapy in Chinese patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy. (PubMed, Chin Med J (Engl)) - No abstract available

Journal • Cervical Cancer • Oncology • Solid Tumor

Zai Lab Limited…announced that China’s National Medical Products Administration (NMPA) has approved the Biologics License Application (BLA) for TIVDAK (tisotumab vedotin for injection) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy (Businesswire) - "This approval is based on results from the global, randomized, Phase 3 innovaTV 301 clinical trial, which met its primary endpoint, demonstrating overall survival (OS) benefit in adult patients with previously treated recurrent or metastatic cervical cancer treated with TIVDAK compared to chemotherapy, including in an exploratory subpopulation of patients in China."

China approval • Cervical Cancer