TIVDAK® (tisotumab vedotin) Approved by European Commission for Previously Treated Recurrent or Metastatic Cervical Cancer
Genmab A/S (NASDAQ: GMAB) announced that the European Commission has approved TIVDAK® (tisotumab vedotin) for treating adult patients with recurrent or metastatic cervical cancer who experienced disease progression after systemic therapy. TIVDAK is the first and only antibody-drug conjugate (ADC) approved for this indication in the EU.
The approval is based on the Phase 3 innovaTV 301 trial results, where TIVDAK demonstrated:
- 30% reduction in death risk compared to chemotherapy
- Median overall survival of 11.5 months vs 9.5 months for chemotherapy
- 33% reduction in disease progression risk
Common adverse reactions (≥25%) included peripheral neuropathy (39%), nausea (37%), epistaxis (33%), conjunctivitis (32%), alopecia (31%), anaemia (27%), and diarrhoea (25%).
Genmab A/S (NASDAQ: GMAB) ha annunciato che la Commissione Europea ha approvato TIVDAK® (tisotumab vedotin) per il trattamento di pazienti adulti con carcinoma cervicale ricorrente o metastatico che hanno mostrato progressione della malattia dopo terapia sistemica. TIVDAK è il primo e unico coniugato anticorpale-farmaco (ADC) approvato per questa indicazione nell'UE.
L'approvazione si basa sui risultati dello studio di Fase 3 innovaTV 301, dove TIVDAK ha dimostrato:
- riduzione del 30% del rischio di morte rispetto alla chemioterapia
- una sopravvivenza globale mediana di 11,5 mesi contro 9,5 mesi per la chemioterapia
- riduzione del 33% del rischio di progressione della malattia
Le reazioni avverse comuni (≥25%) includevano neuropatia periferica (39%), nausea (37%), epistassi (33%), congiuntivite (32%), alopecia (31%), anemia (27%) e diarrea (25%).
Genmab A/S (NASDAQ: GMAB) anunció que la Comisión Europea ha aprobado TIVDAK® (tisotumab vedotin) para el tratamiento de pacientes adultos con cáncer cervical recurrente o metastásico que experimentaron progresión de la enfermedad después de la terapia sistémica. TIVDAK es el primer y único conjugado anticuerpo-fármaco (ADC) aprobado para esta indicación en la UE.
La aprobación se basa en los resultados del ensayo de Fase 3 innovaTV 301, donde TIVDAK demostró:
- una reducción del 30% en el riesgo de muerte en comparación con la quimioterapia
- una supervivencia global media de 11,5 meses frente a 9,5 meses para la quimioterapia
- una reducción del 33% en el riesgo de progresión de la enfermedad
Las reacciones adversas comunes (≥25%) incluyeron neuropatía periférica (39%), náuseas (37%), epistaxis (33%), conjuntivitis (32%), alopecia (31%), anemia (27%) y diarrea (25%).
Genmab A/S (NASDAQ: GMAB)는 유럽연합 집행위원회가 TIVDAK® (tisotumab vedotin)을 전신 요법 후 질병 진행이 있었던 성인 재발성 또는 전이성 자궁경부암 환자 치료를 위해 승인했다고 발표했습니다. TIVDAK는 이 적응증에 대해 EU에서 승인된 첫 번째이자 유일한 항체-약물 접합체(ADC)입니다.
이번 승인은 TIVDAK가 다음을 입증한 3상 innovaTV 301 임상 시험 결과를 기반으로 합니다:
- 화학요법에 비해 30% 사망 위험 감소
- 화학요법의 9.5개월에 비해 11.5개월의 중앙 전체 생존 기간
- 질병 진행 위험 33% 감소
일반적인 부작용(≥25%)으로는 말초 신경병증(39%), 메스꺼움(37%), 비출혈(33%), 결막염(32%), 탈모(31%), 빈혈(27%), 설사(25%)가 포함되었습니다.
Genmab A/S (NASDAQ: GMAB) a annoncé que la Commission européenne a approuvé TIVDAK® (tisotumab vedotin) pour le traitement des patients adultes atteints d'un cancer du col de l'utérus récurrent ou métastatique ayant présenté une progression de la maladie après une thérapie systémique. TIVDAK est le premier et unique conjugé anticorps-médicament (ADC) approuvé pour cette indication dans l'UE.
Cette approbation est basée sur les résultats de l'essai de phase 3 innovaTV 301, où TIVDAK a démontré :
- une réduction de 30 % du risque de décès par rapport à la chimiothérapie
- une survie globale médiane de 11,5 mois contre 9,5 mois pour la chimiothérapie
- une réduction de 33 % du risque de progression de la maladie
Les réactions indésirables courantes (≥25 %) comprenaient neuropathie périphérique (39 %), nausées (37 %), épistaxis (33 %), conjonctivite (32 %), alopécie (31 %), anémie (27 %) et diarrhée (25 %).
Genmab A/S (NASDAQ: GMAB) gab bekannt, dass die Europäische Kommission TIVDAK® (tisotumab vedotin) zur Behandlung von erwachsenen Patienten mit rezidivierendem oder metastasiertem Zervixkarzinom, die nach einer systemischen Therapie eine Krankheitsprogression erfahren haben, genehmigt hat. TIVDAK ist der erste und einzige Antikörper-Wirkstoff-Konjugat (ADC), das für diese Indikation in der EU zugelassen ist.
Die Genehmigung basiert auf den Ergebnissen der Phase-3-Studie innovaTV 301, in der TIVDAK folgendes zeigte:
- 30% Reduktion des Sterberisikos im Vergleich zur Chemotherapie
- Medianes Gesamtüberleben von 11,5 Monaten gegenüber 9,5 Monaten bei Chemotherapie
- 33% Reduktion des Risikos einer Krankheitsprogression
Häufige Nebenwirkungen (≥25%) umfassten periphere Neuropathie (39%), Übelkeit (37%), Nasenbluten (33%), Bindehautentzündung (32%), Haarausfall (31%), Anämie (27%) und Durchfall (25%).
- First and only ADC approved for recurrent/metastatic cervical cancer in EU
- Superior overall survival benefit vs chemotherapy (11.5 vs 9.5 months)
- 30% reduction in death risk compared to chemotherapy
- 33% reduction in disease progression risk
- Expansion into European market creates new revenue opportunity
- Significant adverse reactions reported in ≥25% of patients
- efficacy with median survival benefit of only 2 months
Insights
The EC approval of TIVDAK for recurrent or metastatic cervical cancer represents a significant therapeutic advancement for a patient population with treatment options. The drug demonstrated a
What's particularly noteworthy is TIVDAK's novel mechanism as an antibody-drug conjugate (ADC). This technology precisely delivers cytotoxic payloads to cancer cells while minimizing damage to healthy tissue. The
The approval's clinical significance extends beyond statistical endpoints. For patients with disease progression after systemic therapy, therapeutic options have historically been , with poor prognoses. TIVDAK addresses this critical treatment gap with a manageable safety profile despite expected ADC-associated toxicities like peripheral neuropathy (
With this third major market approval (after US and Japan), TIVDAK is positioned to potentially become a new standard of care in the second-line setting for advanced cervical cancer, replacing conventional chemotherapy with its modest efficacy and challenging toxicity profile.
This European Commission approval significantly strengthens Genmab's commercial position in oncology. As the first and only ADC approved for recurrent or metastatic cervical cancer in the EU, TIVDAK enjoys first-mover advantage in a treatment landscape with substantial unmet needs.
The approval represents a crucial milestone as it marks Genmab's first independent European commercialization effort. This evolution from primarily licensing its technologies to bringing products to market independently demonstrates the company's strategic transition into a fully integrated biopharmaceutical company with end-to-end capabilities.
The robust Phase 3 data showing superior survival benefits provides compelling clinical differentiation from existing chemotherapy options. This positions TIVDAK favorably for inclusion in European treatment guidelines and reimbursement decisions, though country-by-country negotiations will determine ultimate market access and uptake rates.
The cervical cancer indication, while not among the most common cancers, represents a strategically sound initial market. With cervical cancer ranking as the 11th most frequent cancer among European women and up to
This approval further validates Genmab's ADC technology platform and strengthens their position in the rapidly expanding ADC market segment, potentially enhancing the company's partnership opportunities and pipeline valuation for future ADC candidates.
- TIVDAK® is the first and only antibody-drug conjugate (ADC) approved to treat recurrent or metastatic cervical cancer with disease progression on or after systemic therapy
- In the global Phase 3 innovaTV 301 clinical trial TIVDAK demonstrated superior overall survival compared to chemotherapy
-
TIVDAK is approved for the treatment of recurrent or metastatic cervical cancer in the European Union,
United States andJapan
Despite progress in cervical cancer prevention and early detection, there remains a high need for new treatment options, particularly in advanced forms of the disease. In fact, cervical cancer is the fourth most common cause of cancer death among women globally.i In the European Union, cervical cancer is the 11th most frequently occurring cancer among women.ii Up to
“Recurrent or metastatic cervical cancer is a devastating disease, and patients can face a difficult treatment journey with limited options,” said Ignace Vergote, M.D., Ph.D., University Hospitals Leuven, co-founder of European Network of Gynaecological Oncological Trial groups (ENGOT), and lead investigator on the innovaTV 301 clinical trial. “In clinical trials, TIVDAK demonstrated a superior overall survival benefit and manageable safety profile compared to chemotherapy, supporting its position to become a potential new standard of care in this setting with a novel mechanism of action. This approval is an important step forward in the treatment landscape for advanced 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. The trial met its primary endpoint of overall survival (OS), demonstrating a
The most common (≥
“We recognize the urgent need to accelerate science and innovate new treatment options for gynecologic cancers, including cervical cancer,” said Brad Bailey, Executive Vice President and Chief Commercial Officer of Genmab. “The European Commission approval of TIVDAK marks a milestone in our work to transform the treatment paradigm and help improve outcomes for patients. As the first medicine that Genmab will bring to patients in
About the innovaTV 301 Trial
The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating tisotumab vedotin versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who received one or two prior systemic regimens in the recurrent or metastatic setting.
Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology, and disease progression during or after treatment with chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint was overall survival. The main secondary outcomes were progression-free survival and objective response rate.
The study was conducted by Seagen, which was acquired by Pfizer in December 2023, in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057), as well as other global gynecological oncology cooperative groups. For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.
About Tisotumab Vedotin
Tisotumab vedotin (approved under the brand name TIVDAK® in the EU,
About the Pfizer and Genmab Collaboration
Tisotumab vedotin is co-developed and co-commercialized globally by Genmab and Pfizer, under an agreement in which the companies share costs and profits.
With respect to the commercialization of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer, Genmab leads commercialization in
Pfizer is currently the marketing authorization holder (MAH) for tisotumab vedotin in the European Union. This responsibility is expected to transfer to Genmab in 2025.
TIVDAK® (tisotumab vedotin-tftv)
Indication
TIVDAK is a tissue factor-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
Important Safety Information
BOXED WARNING: OCULAR TOXICITY
TIVDAK can cause severe ocular toxicities resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam, including an assessment of ocular symptoms, visual acuity, and slit lamp exam of the anterior segment of the eye prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated. Adhere to the required premedication and eye care before, during, and after infusion. Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity.
Warnings and Precautions
Ocular adverse reactions: TIVDAK can cause severe ocular adverse reactions, including conjunctivitis, keratopathy (keratitis, punctate keratitis, and ulcerative keratitis), and dry eye (increased lacrimation, eye pain, eye discharge, pruritus, irritation, and foreign body sensation), that may lead to changes in vision and/or corneal ulceration.
Ocular adverse reactions occurred in
In innovaTV 301, 8 patients (
Refer patients to an eye care provider to conduct an ophthalmic exam prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated. The exam should include visual acuity, slit lamp exam of the anterior segment of the eye, and an assessment of normal eye movement and ocular signs or symptoms which include dry or irritated eyes, eye secretions, or blurry vision.
Adhere to the required premedication and eye care before, during, and after infusion to reduce the risk of ocular adverse reactions. Monitor for ocular toxicity and promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold, reduce, or permanently discontinue TIVDAK based on the severity or persistence of the ocular adverse reaction.
Peripheral Neuropathy (PN) occurred in
Monitor patients for signs and symptoms of neuropathy such as paresthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia. For new or worsening PN, withhold, then dose reduce, or permanently discontinue TIVDAK based on the severity of PN.
Hemorrhage occurred in
Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or central nervous system hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK.
Pneumonitis that is severe, life-threatening, or fatal can occur in patients treated with antibody-drug conjugates containing vedotin, including TIVDAK. Among cervical cancer patients treated with TIVDAK across clinical trials, 4 patients (
Monitor patients for pulmonary symptoms of pneumonitis. Symptoms may include hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations. Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis.
Severe cutaneous adverse reactions (SCAR), including events of fatal or life-threatening Stevens-Johnson syndrome (SJS), can occur in patients treated with TIVDAK. SCAR occurred in
Monitor patients for signs or symptoms of SCAR, which include target lesions, worsening skin reactions, blistering or peeling of the skin, painful sores in mouth, nose, throat, or genital area, fever or flu-like symptoms, and swollen lymph nodes. If signs or symptoms of SCAR occur, withhold TIVDAK until the etiology of the reaction has been determined. Early consultation with a specialist is recommended to ensure greater diagnostic accuracy and appropriate management. Permanently discontinue TIVDAK for confirmed Grade 3 or 4 SCAR, including SJS.
Embryo-fetal toxicity: TIVDAK can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.
Adverse Reactions
Across clinical trials of TIVDAK in 425 patients with r/mCC, the most common (≥
innovaTV 301 Study: 250 patients with r/mCC with disease progression on or after systemic therapy
Serious adverse reactions occurred in
Adverse reactions leading to permanent discontinuation occurred in
innovaTV 204 Study: 101 patients with r/mCC with disease progression on or after chemotherapy
Serious adverse reactions occurred in
Adverse reactions leading to permanent discontinuation occurred in
Drug Interactions
Strong CYP3A4 inhibitors: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for TIVDAK adverse reactions.
Use in Specific Populations
Moderate or severe hepatic impairment: MMAE exposure and adverse reactions are increased. Avoid use.
Lactation: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.
Please see full
About Genmab
Genmab is an international biotechnology company with a core purpose of guiding its unstoppable team to strive toward improving the lives of patients with innovative and differentiated antibody therapeutics. For more than 25 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational, quantitative and data sciences, resulting in a proprietary pipeline including bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators and effector function-enhanced antibodies. By 2030, Genmab’s vision is to transform the lives of people with cancer and other serious diseases with knock-your-socks-off (KYSO®) antibody medicines.
Established in 1999, Genmab is headquartered in
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____________________ i Wu, Jie, and Qianyun Jin. “Global Burden of Cervical Cancer: Current Estimates, Temporal Trend and Future Projections Based on the Globocan 2022.” Journal of the National Cancer Center, 23 Jan. 2025, www.sciencedirect.com/science/article/pii/S2667005425000134. ii “Cervical Cancer Burden in EU-27 - Europa.Eu.” Cancer Factsheets in EU-27 Countries, ECIS - European Cancer Information System, 17 Nov. 2021, https://ecis.jrc.ec.europa.eu/sites/default/files/2023-12/cervical_cancer_en-Nov_2021.pdf. iii National Cancer Institute. SEER Cancer Stat Facts: Cervical Cancer. 2023. https://seer.cancer.gov/statfacts/html/cervix.html. iv McLachlan J, Boussios S, Okines A, et al. The impact of systemic therapy beyond first-line treatment for advanced cervical cancer. Clin Oncol (R Coll Radiol). 2017;29(3):153-60. v Pfaendler KS, Tewari KS. Changing paradigms in the systemic treatment of advanced cervical cancer. Am J Obstet Gynecol. 2016 Jan;214(1):22-30. doi: 10.1016/j.ajog.2015.07.022. Epub 2015 Jul 26. PMID: 26212178; PMCID: PMC5613936.
vi Gennigens, C., |
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