Seagen to Highlight Research in Urothelial Cancer at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium

Rhea-AI Summary

Seagen Inc. (NASDAQ: SGEN) has announced the presentation of new data for PADCEV (enfortumab vedotin) at the ASCO-GU symposium from February 16-18, 2023. The study focuses on patient-reported outcomes from the Phase 1b/2 EV-103 Cohort K, which evaluates PADCEV alone and with KEYTRUDA in patients with unresectable locally advanced or metastatic urothelial cancer. Additional analyses will include the confirmed objective response rate and qualitative insights from patients and caregivers, showcasing Seagen's commitment to addressing unmet clinical needs in urothelial cancer.

Positive

• Presentation of new data for PADCEV at ASCO-GU emphasizes its potential in treating urothelial cancer.
• Patient-reported outcomes demonstrate Seagen's focus on quality of life for patients.
• Partnership with Merck for combination therapy with KEYTRUDA enhances treatment options.

Negative

• None.

- Data presentations demonstrate continued potential of PADCEV^® (enfortumab vedotin-ejfv) in multiple types of urothelial cancer -

- Patient-reported outcomes underscore Seagen’s commitment to addressing patients’ needs and quality of life -

BOTHELL, Wash.--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq: SGEN) today announced the presentation of new data featuring PADCEV^® (enfortumab vedotin-ejfv) at the upcoming American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) taking place from February 16-18, 2023. A podium presentation will feature noteworthy patient-reported outcomes from the registrational Phase 1b/2 EV‐103 Cohort K study.

Cohort K is evaluating enfortumab vedotin developed in partnership with Astellas, as monotherapy and in combination with Merck’s anti-PD-1 therapy KEYTRUDA^® (pembrolizumab) as first-line treatment in patients with unresectable locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible to receive cisplatin-based chemotherapy. Merck is known as MSD outside the United States and Canada.

“Patients are at the heart of the work we do, and we are committed to developing innovative solutions for people with urothelial cancer and challenging clinical needs,” said Marjorie Green, M.D., Senior Vice President and Head of Late-Stage Development, Seagen. “We look forward to presenting patient-reported outcomes for PADCEV at ASCO GU, and further addressing unmet needs that people with cancer experience in order to better support this community and increase their quality of life.”

Other notable data that will be presented from Seagen’s sponsored research include subgroup analyses of the confirmed objective response rate by investigator assessment from the EV‐103 Cohort K study, along with qualitative insights from patients, caregivers and physicians and data from real-world studies. Trials in progress for enfortumab vedotin in non-muscle invasive and muscle-invasive bladder cancer will also be featured in poster presentations at the meeting, showcasing Seagen’s engagement across a broad spectrum of urothelial cancers.

Key data presentations for Seagen include:

Presentations of Company-Sponsored Trials

Abstract Title	Abstract #	Presentation Time	Lead Author
Enfortumab Vedotin
Patient‐reported outcomes (PROs) in cisplatin‐ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) treated with enfortumab vedotin (EV) alone or in combination with pembrolizumab (P) in the Phase 1b/2 EV‐103 Cohort K study	439	Podium Presentation Friday, Feb. 17 3:45-3:55 p.m. PT   Panel Discussion 3:55 p.m. PT	M. Milowsky
Enfortumab vedotin (EV) alone or in combination w/ pembrolizumab (P) in previously untreated cisplatin‐ineligible patients w/ locally advanced or metastatic urothelial cancer (la/mUC): Subgroup analyses of confirmed objective response rate (cORR) from EV‐103 Cohort K	499	Poster Session Friday, Feb. 17 12:30-2 p.m. PT 5:15-6:15 p.m. PT	P. O’Donnell
Understanding drivers of treatment preferences in locally advanced or metastatic urothelial carcinoma: A qualitative interview study with patients, caregivers, and physicians	492	Poster Session Friday, Feb. 17 12:30-2 p.m. PT 5:15-6:15 p.m. PT	A. Apolo
Real‐World treatment and quality of life (QOL) in locally advanced or metastatic urothelial carcinoma (la/mUC) in Saudi Arabia, Singapore, South Korea, Taiwan, and Turkey	462	Poster Session Friday, Feb. 17 12:30-2 p.m. PT 5:15-6:15 p.m. PT	L. Cheng
Real‐World treatment patterns, survival outcomes, and health care resource utilization (HCRU) for Locally Advanced or Metastatic Urothelial Carcinoma (la/mUC) in Spain	463	Poster Session Friday, Feb. 17 12:30-2 p.m. PT 5:15-6:15 p.m. PT	J. Puente
Disitamab Vedotin
Systematic literature review and testing of HER2 status in urothelial carcinoma (UC)	556	Poster Session Friday, Feb. 17 12:30-2 p.m. PT 5:15-6:15 p.m. PT	V. Koshkin

Presentations of Company-Sponsored Trials in Progress

Abstract Title	Abstract #	Presentation Type	Lead Author
Enfortumab Vedotin
Study EV‐104: Phase 1 study of intravesical enfortumab vedotin for treatment of patients with non‐muscle invasive bladder cancer (NMIBC) (Encore) (TIP)	TPS582	Poster Session Friday, Feb. 17 12:30 p.m. PT	A. Kamat
Phase 3 KEYNOTE‐905/EV‐303: Perioperative pembrolizumab (pembro) or pembro + enfortumab vedotin (EV) for muscle‐invasive bladder cancer (MIBC) (Encore) (TIP)	TPS585	Poster Session Friday, Feb. 17 12:30 p.m. PT	A. Necchi
Perioperative enfortumab vedotin (EV) plus pembrolizumab (pembro) versus chemotherapy in cisplatin‐eligible patients (pts) with muscle‐invasive bladder cancer (MIBC): Phase 3 KEYNOTE‐B15/EV‐304 (Encore) (TIP)	TPS588	Poster Session Friday, Feb. 17 12:30 p.m. PT	C. Hoimes
Tucatinib
A Phase 2 basket study of tucatinib and trastuzumab in previously treated solid tumors with HER2 alterations: urothelial cancer cohort (TIP)	TPS587	Poster Session Friday, Feb. 17 12:30 p.m. PT	E. Yu
Disitamab Vedotin
A Phase 2 clinical study evaluating the efficacy and safety of disitamab vedotin with or without pembrolizumab in patients with HER2-expressing urothelial carcinoma (TIP)	TPS594	Poster Session Friday, Feb. 17 12:30 p.m. PT	T. Powles

About Enfortumab Vedotin

Enfortumab vedotin is an antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.^i,ii Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).i

PADCEV (enfortumab vedotin-ejfv) U.S. Indication & Important Safety Information
BOXED WARNING: SERIOUS SKIN REACTIONS

• PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later.
• Closely monitor patients for skin reactions.
• Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions.
• Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

Indication

PADCEV^® is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who:

• have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or
• are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.ⁱⁱⁱ

Important Safety Information
Warnings and Precautions

Skin reactions Severe cutaneous adverse reactions, including fatal cases of SJS or TEN, occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. Skin reactions occurred in 55% of the 680 patients treated with PADCEV in clinical trials. Twenty-three percent (23%) of patients had maculo-papular rash and 33% had pruritus. Grade 3-4 skin reactions occurred in 13% of patients, including maculo-papular rash, rash erythematous, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In clinical trials, the median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 6.4). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=59), 24% of patients restarting at the same dose and 16% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 2.6% of patients. Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. Withhold PADCEV and refer for specialized care for suspected SJS or TEN or for severe (Grade 3) skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN, or for Grade 4 or recurrent Grade 3 skin reactions.

Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV. Patients with baseline hemoglobin A1C ≥8% were excluded from clinical trials. In clinical trials, 14% of the 680 patients treated with PADCEV developed hyperglycemia; 7% of patients developed Grade 3-4 hyperglycemia. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. The median time to onset of hyperglycemia was 0.6 months (range: 0.1 to 20.3). Hyperglycemia led to discontinuation of PADCEV in 0.6% of patients. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

Pneumonitis Severe, life-threatening or fatal pneumonitis occurred in patients treated with PADCEV. In clinical trials, 3.1% of the 680 patients treated with PADCEV had pneumonitis of any grade and 0.7% had Grade 3-4. In clinical trials, the median time to onset of pneumonitis was 2.9 months (range: 0.6 to 6). Monitor patients for signs and symptoms indicative of pneumonitis, such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations. Withhold PADCEV for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis.

Peripheral neuropathy (PN) occurred in 52% of the 680 patients treated with PADCEV in clinical trials, including 39% with sensory neuropathy, 7% with muscular weakness and 6% with motor neuropathy; 4% experienced Grade 3-4 reactions. PN occurred in patients treated with PADCEV with or without preexisting PN. The median time to onset of Grade ≥2 PN was 4.6 months (range: 0.1 to 15.8 months). Neuropathy led to treatment discontinuation in 5% of patients. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when PN occurs. Permanently discontinue PADCEV in patients who develop Grade ≥3 PN.

Ocular disorders were reported in 40% of the 384 patients treated with PADCEV in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy. Dry eye symptoms occurred in 34% of patients, and blurred vision occurred in 13% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.6 months (range: 0 to 19.1 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 680 patients, 1.6% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Two patients (0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

Adverse Reactions
Most Common Adverse Reactions, Including Laboratory Abnormalities (≥20%)

Rash, aspartate aminotransferase (AST) increased, glucose increased, creatinine increased, fatigue, PN, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase (ALT) increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased and dry skin.

EV-301 Study: 296 patients previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapy.

Serious adverse reactions occurred in 47% of patients treated with PADCEV; the most common (≥2%) were urinary tract infection, acute kidney injury (7% each) and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1.0%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis and pelvic abscess (0.3% each). Adverse reactions leading to discontinuation occurred in 17% of patients; the most common (≥2%) were PN (5%) and rash (4%). Adverse reactions leading to dose interruption occurred in 61% of patients; the most common (≥4%) were PN (23%), rash (11%) and fatigue (9%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common (≥2%) were PN (10%), rash (8%), decreased appetite and fatigue (3% each). Clinically relevant adverse reactions (<15%) include vomiting (14%), AST increased (12%), hyperglycemia (10%), ALT increased (9%), pneumonitis (3%) and infusion site extravasation (0.7%).

EV-201, Cohort 2 Study: 89 patients previously treated with a PD-1/L1 inhibitor and not eligible for platinum-based chemotherapy.

Serious adverse reactions occurred in 39% of patients treated with PADCEV; the most common (≥3%) were pneumonia, sepsis and diarrhea (5% each). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia and pneumonitis (1.1% each). Adverse reactions leading to discontinuation occurred in 20% of patients; the most common (≥2%) was PN (7%). Adverse reactions leading to dose interruption occurred in 60% of patients; the most common (≥3%) were PN (19%), rash (9%), fatigue (8%), diarrhea (5%), AST increased and hyperglycemia (3% each). Adverse reactions leading to dose reduction occurred in 49% of patients; the most common (≥3%) were PN (19%), rash (11%) and fatigue (7%). Clinically relevant adverse reactions (<15%) include vomiting (13%), AST increased (12%), lipase increased (11%), ALT increased (10%), pneumonitis (4%) and infusion site extravasation (1%).

Drug Interactions
Effects of other drugs on PADCEV (Dual P-gp and Strong CYP3A4 Inhibitors)

Concomitant use with a dual P-gp and strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with dual P-gp and strong CYP3A4 inhibitors.

Specific Populations

Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

For more information, please see the full Prescribing Information including BOXED WARNING for PADCEV here.

About Seagen

Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people’s lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

Forward-Looking Statements

Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of PADEV, TUKYSA^® (tucatinib), disitamab vedotin, and the company’s other products and product candidates, including their potential efficacy, safety and therapeutic uses, and Seagen’s pipeline. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include without limitation the difficulty and uncertainty of pharmaceutical product development, including the risks that the company may experience delays in its clinical trials or otherwise experience failures or setbacks in its clinical development programs due to lack of efficacy, adverse events or other factors, and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seagen is contained under the caption “Risk Factors” included in the company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2022, filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

ⁱ PADCEV [package insert]. Northbrook, Ill.: Astellas Pharma US, Inc.
ⁱⁱ Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.
ⁱⁱⁱ Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021; 10.1056/NEJMoa2035807.

View source version on businesswire.com: https://www.businesswire.com/news/home/20230213005101/en/

For Media

David Caouette

(310) 430-3476

dcaouette@seagen.com

For Investors

Douglas Maffei, Ph.D.

(425) 527-4160

dmaffei@seagen.com

Source: Seagen Inc.

FAQ

What new data is being presented by Seagen Inc. for SGEN?

Seagen is presenting new data on PADCEV at the ASCO-GU symposium, focusing on patient-reported outcomes in urothelial cancer.

When is the ASCO-GU symposium where Seagen will present data?

The ASCO-GU symposium will take place from February 16-18, 2023.

What is the significance of the EV-103 Cohort K study for PADCEV?

The EV-103 Cohort K study evaluates PADCEV both as a monotherapy and in combination with KEYTRUDA for patients ineligible for cisplatin-based chemotherapy.

Who is collaborating with Seagen in the development of PADCEV?

Seagen is collaborating with Merck on the development of PADCEV in combination with KEYTRUDA.

What patient population is targeted in the EV-103 study for PADCEV?

The EV-103 study targets patients with unresectable locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-based chemotherapy.