Investigational Tisotumab Vedotin Phase 2 Data Demonstrates Encouraging Antitumor Activity in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
Genmab announced Phase 2 results from the innovaTV 207 trial, showing that tisotumab vedotin demonstrated encouraging antitumor activity in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The study, presented at the 2024 ASCO Annual Meeting, revealed a 32.5% confirmed objective response rate (cORR) with one complete response and 12 partial responses. Median duration of response was 5.6 months, and median time-to-response was 1.4 months. The study highlighted treatment options for these patients, emphasizing the need for further clinical development. Safety findings were consistent with previous trials, with the most common Grade ≥3 treatment-emergent adverse events being peripheral neuropathy (40%).
- 32.5% confirmed objective response rate (cORR) in HNSCC patients.
- One patient achieved a complete response (CR) and 12 patients achieved partial responses (PR).
- Median duration of response (DOR) was 5.6 months.
- Median time-to-response (TTR) was 1.4 months.
- 40% cORR achieved among patients with no more than one or two lines of prior therapy.
- Safety findings consistent with previous trials, no new safety signals observed.
- 67.5% of patients experienced Grade ≥3 treatment-emergent adverse events (TEAEs).
- 40% of patients experienced peripheral neuropathy events.
- Adverse events of special interest included ocular (52.5%), peripheral neuropathy (47.5%), and bleeding events (40%).
- High prior treatment rates among patients: 80% had previous platinum-based therapy, 100% had prior checkpoint inhibitor (CPI) therapy.
The data from the Phase 2 innovaTV 207 trial highlights an encouraging antitumor activity of tisotumab vedotin, with a confirmed objective response rate (cORR) of
A critical aspect to note is the median duration of response (DOR) of 5.6 months, which indicates the treatment's efficacy duration. Investors should weigh this against the high incidence of Grade ≥3 treatment-emergent adverse events (TEAEs) occurring in
From a clinical standpoint, the innovaTV 207 trial results for tisotumab vedotin in patients with recurrent or metastatic HNSCC are quite notable. The objective response rate (32.5%) and the occurrence of a complete response (CR) in one patient are promising, particularly in a heavily pre-treated population where treatment options are typically exhausted. The rapid time-to-response (TTR) of 1.4 months also suggests a fairly quick onset of action, which is beneficial for patients facing aggressive disease.
However, the high rate of adverse events, especially peripheral neuropathy (40%), ocular events (52.5%) and bleeding events (40%), must be considered. These side effects could impact the overall quality of life for patients and may necessitate supportive care measures. The data supports further clinical exploration but underscores the need for balancing efficacy with safety.
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Results from innovaTV207 evaluating tisotumab vedotin, showing
32.5% confirmed objective response rate in patients with recurrent or metastatic HNSCC, presented in a rapid oral session at 2024 ASCO® Annual Meeting -
HNSCC is the sixth most common cancer worldwide, with incidence rates expected to increase
30% by 2030i
In the HNSCC cohort of innovaTV 207 Part C (n=40), median duration of response (DOR) was 5.6 months and median time-to-response (TTR) was 1.4 months. All patients were required to have received a platinum-based regimen in the recurrent or metastatic setting or have persistent disease following platinum-based chemoradiation and a checkpoint inhibitor (CPI), if eligible. The study also showed that among patients with no more than one or two lines of therapy in the recurrent or metastatic setting (n=25),
“Most patients with recurrent or metastatic head and neck squamous cell carcinoma experience disease progression despite the use of platinum-based therapy and immunotherapy, and treatment options are limited,” said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab, “These updated results underscore the importance of our ongoing work with our partner to advance the clinical development program for tisotumab vedotin and investigate potential treatment options for pretreated patients living with unmet needs.”
The safety findings were consistent with previous tisotumab vedotin trials, and no new safety signals were observed. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in
As of December 2023, 40 patients with recurrent or metastatic HNSCC were treated with tisotumab vedotin monotherapy (1.7 mg/kg intravenously, once every two weeks). In this cohort, 32 (
About the innovaTV 207 Trial
The innovaTV 207 trial (NCT03485209) is an open-label, global, Phase 2, multicohort, multicenter study evaluating tisotumab vedotin monotherapy or in combination for advanced solid tumors. In Part C, patients with recurrent or metastatic HNSCC received tisotumab vedotin monotherapy (1.7 mg/kg IV once every two weeks). All patients were required to have received a platinum-based regimen, either in the recurrent/metastatic setting, or to have persistent disease following platinum-based chemoradiation and a checkpoint inhibitor, if eligible. The primary endpoint of the trial is confirmed objective response rate (cORR) per RECIST 1.1 per investigator, defined as the proportion of patients who achieve a confirmed complete or partial response. Selected secondary endpoints include duration of response (DOR), time-to-response (TTR), and safety. For more information about the phase 2 innovaTV 207 clinical trial of tisotumab vedotin, please visit www.clinicaltrials.gov.
About Tisotumab Vedotin
Tisotumab vedotin is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin-tftv is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin-tftv also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.
Tisotumab vedotin (TIVDAK®) has received full approval by the
See TIVDAK
Indication
TIVDAK is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer (r/mCC) 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 prescribing information, including BOXED WARNING for TIVDAK here.
Virtual mid- to late-stage pipeline update at ASCO 2024
On Monday, June 3, at 9:00 AM CDT (10:00 AM EDT/4:00 PM CEST), Genmab will host a review of data presented at ASCO from its mid- to late-stage pipeline. The event will be virtual and webcast live. Details, including the webcast link and registration will be available on www.genmab.com. This meeting is not an official program of the ASCO Annual Meeting.
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 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
About the Pfizer and Genmab Collaboration
Tisotumab vedotin is co-owned by Genmab and Pfizer, under an agreement in which the companies share costs and profits for the product on a 50:50 basis.
This Media Release contains forward looking statements. The words “believe,” “expect,” “anticipate,” “intend” and “plan” and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab’s most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab’s most recent Annual Report on Form 20-F and other filings with the
Genmab A/S and/or its subsidiaries own the following trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in combination with the Y-shaped Genmab logo®; HuMax®; DuoBody®; HexaBody®; DuoHexaBody®, HexElect® and KYSO™. Tivdak® is a trademark of Pfizer Inc.
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i Johnson, Daniel E., et al. “Head and Neck Squamous Cell Carcinoma.” Nature Reviews Disease Primers, Nature Publishing Group, 26 Nov. 2020, https://www.nature.com/articles/s41572-020-00224-3#Fig2.
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FAQ
What is the confirmed objective response rate (cORR) for tisotumab vedotin in HNSCC patients?
How many patients achieved a complete response in the innovaTV 207 trial?
What were the common treatment-emergent adverse events in the Phase 2 trial of tisotumab vedotin?
What was the median duration of response (DOR) for tisotumab vedotin in HNSCC patients?
How long was the median time-to-response (TTR) for tisotumab vedotin in HNSCC patients?