Seagen Announces Results from Pivotal MOUNTAINEER Trial Demonstrating Clinically Meaningful Antitumor Activity of TUKYSA® (tucatinib) in Combination with Trastuzumab in Previously Treated HER2-Positive Metastatic Colorectal Cancer

–Part 2 trial confirmed chemotherapy-free TUKYSA mixture resulted in clinically significant and sturdy tumor responses–

–Outcomes offered in late-breaking oral session on the ESMO World Congress on Gastrointestinal Most cancers–

BOTHELL, Wash.–(BUSINESS WIRE)–Seagen Inc. (Nasdaq:SGEN) right now introduced full outcomes from the pivotal section 2 MOUNTAINEER trial, which confirmed TUKYSA^® (tucatinib) together with trastuzumab was well-tolerated with sturdy responses in sufferers with beforehand handled HER2-positive metastatic colorectal most cancers (mCRC). These late-breaking information have been offered in an oral session on the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Most cancers on July 2 in Barcelona, Spain.

“Sufferers with chemotherapy-refractory HER2-positive metastatic colorectal most cancers obtain restricted scientific profit with at the moment obtainable therapies,” stated John H. Strickler, M.D., Affiliate Professor of Medication, Duke College College of Medication and lead trial investigator. “With sustained responses and favorable tolerability in closely pretreated sufferers, tucatinib together with trastuzumab has the potential to be a brand new therapy possibility for beforehand handled HER2-positive mCRC.”

“This research has proven the advantages of dual-HER2 inhibition with tucatinib and trastuzumab in sufferers with HER2-positive metastatic colorectal most cancers, together with many whose most cancers had unfold to the liver or lungs earlier than becoming a member of the trial,” stated Roger Dansey, M.D., interim CEO and Chief Medical Officer, Seagen. “We consider this chemotherapy-free mixture might play an necessary position in addressing the unmet wants of sufferers with this illness.”

At a median length of follow-up of 20.7 months (interquartile vary: 11.7, 39.0), outcomes of the MOUNTAINEER trial confirmed a 38.1% confirmed goal response price (cORR) (95% Confidence Interval [CI]: 27.7, 49.3) per blinded unbiased central evaluate (BICR) within the HER2-positive sufferers who have been assigned to obtain tucatinib together with trastuzumab (n=84 with a median age of 55.0 years [range 24 to 77]). In these sufferers, the median length of response (DoR) per BICR was 12.4 months (95% CI: 8.5, 20.5). Median progression-free survival per BICR was 8.2 months (95% CI: 4.2, 10.3), and median general survival was 24.1 months (95% CI: 20.3, 36.7). At research entry, 64.3% and 70.2% of those sufferers had liver or lung metastases, respectively, and had obtained a median of three.0 (1, 6) prior traces of systemic remedy.

In a cohort of sufferers who obtained tucatinib monotherapy (n=30), the ORR per BICR by 12 weeks was 3.3% (95% CI: 0.1, 17.2) and the illness management price was 80.0%. Contributors who didn’t reply to tucatinib monotherapy by 12 weeks or progressed at any time had the choice to obtain the mix of tucatinib and trastuzumab.

The commonest (higher than or equal to twenty%) treatment-emergent hostile occasions (AEs) in sufferers assigned to obtain tucatinib and trastuzumab (n=86) have been diarrhea (Grade 1 or 2: 60.5%, Grade 3: 3.5%), fatigue (Grade 1 or 2: 41.9%, Grade 3: 2.3%), nausea (Grade 1 or 2: 34.9%) and infusion-related response (Grade 1 or 2: 20.9%). The commonest Grade ≥3 AE was hypertension (Grade 3: 7.0%). AEs resulting in discontinuation of any therapy occurred in 5.8% of sufferers. No deaths as a consequence of AEs have been reported. Please see Essential Security Data on the finish of this press launch for additional security info relating to tucatinib.

Information from this trial will type the idea of a deliberate supplemental New Drug Utility to the U.S. Meals and Drug Administration underneath the Accelerated Approval Program. Merck, often known as MSD outdoors the U.S. and Canada, has unique rights to commercialize TUKYSA in areas outdoors of the U.S., Canada and Europe and plans to debate these outcomes with sure world well being authorities.

About MOUNTAINEER

MOUNTAINEER is a U.S. and European multicenter, open-label, randomized section 2 scientific trial of tucatinib together with trastuzumab or as a single agent that enrolled 117 sufferers with HER2-positive metastatic or unresectable colorectal most cancers following earlier standard-of-care therapies. MOUNTAINEER started as a U.S. investigator-sponsored trial and initially consisted of a single cohort (Cohort A) of sufferers who obtained tucatinib (300 mg) twice per day orally together with trastuzumab intravenously (8 mg/kg loading dose, then 6 mg/kg each three weeks thereafter). The trial was then expanded globally to incorporate sufferers who have been randomized to obtain tucatinib plus trastuzumab (Cohort B) or tucatinib monotherapy (Cohort C).

The first endpoint of the trial is confirmed goal response price by RECIST (Response Analysis Standards in Stable Tumors) model 1.1 standards per blinded unbiased central evaluate in sufferers receiving the mix of tucatinib and trastuzumab (Cohorts A and B). Length of response, progression-free survival, general survival and security and tolerability of the mix routine are secondary aims.

About Colorectal Most cancers

Globally, greater than 1.9 million new colorectal most cancers circumstances and 935,000 deaths have been estimated to happen in 2020, representing about one in 10 most cancers circumstances and deaths.¹ Colorectal most cancers is the third main reason for cancer-related deaths within the U.S. and is anticipated to result in about 52,580 deaths in 2022.² Roughly 22% of U.S. sufferers with colorectal most cancers are identified on the superior stage.³ Human epidermal progress issue receptor 2 (HER2) is overexpressed in 3-5% of sufferers with metastatic colorectal most cancers.^4,5 There are at the moment no FDA-approved therapies that particularly goal HER2 in colorectal most cancers.

About TUKYSA

TUKYSA is an oral drugs that could be a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab research), TUKYSA inhibited phosphorylation of HER2 and HER3, leading to inhibition of downstream MAPK and AKT signaling and cell progress (proliferation), and confirmed anti-tumor exercise in HER2-expressing tumor cells. In vivo (in residing organisms), TUKYSA inhibited the expansion of HER2-expressing tumors. The mixture of TUKYSA and the anti-HER2 antibody trastuzumab confirmed elevated anti-tumor exercise in vitro and in vivo in comparison with both drugs alone.

TUKYSA is authorized in 36 nations. It was authorized by the U.S. FDA in April 2020 and by the European Medicines Company and the UK Medicines and Healthcare Merchandise Regulatory Company in February 2021. Merck, often known as MSD outdoors the U.S. and Canada, has unique rights to commercialize TUKYSA in Asia, the Center East and Latin America and different areas outdoors of the U.S., Canada and Europe.

U.S. Indication and Essential Security Data

TUKYSA is indicated together with trastuzumab and capecitabine for therapy of grownup sufferers with superior unresectable or metastatic HER2-positive breast most cancers, together with sufferers with mind metastases, who’ve obtained a number of prior anti-HER2-based regimens within the metastatic setting.

Warnings and Precautions

• Diarrhea – TUKYSA may cause extreme diarrhea together with dehydration, hypotension, acute kidney harm, and demise. In HER2CLIMB, 81% of sufferers who obtained TUKYSA skilled diarrhea, together with 12% with Grade 3 diarrhea and 0.5% with Grade 4 diarrhea. Each sufferers who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to demise. The median time to onset of the primary episode of diarrhea was 12 days and the median time to decision was 8 days. Diarrhea led to dose reductions of TUKYSA in 6% of sufferers and discontinuation of TUKYSA in 1% of sufferers. Prophylactic use of antidiarrheal therapy was not required on HER2CLIMB.

  If diarrhea happens, administer antidiarrheal therapy as clinically indicated. Carry out diagnostic checks as clinically indicated to exclude different causes of diarrhea. Primarily based on the severity of the diarrhea, interrupt dose, then dose cut back or completely discontinue TUKYSA.

• Hepatotoxicity – TUKYSA may cause extreme hepatotoxicity. In HER2CLIMB, 8% of sufferers who obtained TUKYSA had an ALT improve >5 × ULN, 6% had an AST improve >5 × ULN, and 1.5% had a bilirubin improve >3 × ULN (Grade ≥3). Hepatotoxicity led to dose discount of TUKYSA in 8% of sufferers and discontinuation of TUKYSA in 1.5% of sufferers.

  Monitor ALT, AST, and bilirubin previous to beginning TUKYSA, each 3 weeks throughout therapy, and as clinically indicated. Primarily based on the severity of hepatotoxicity, interrupt dose, then dose cut back or completely discontinue TUKYSA.

• Embryo-Fetal Toxicity – TUKYSA may cause fetal hurt. Advise pregnant ladies and females of reproductive potential danger to a fetus. Advise females of reproductive potential, and male sufferers with feminine companions of reproductive potential, to make use of efficient contraception throughout TUKYSA therapy and for no less than 1 week after the final dose.

Adversarial Reactions

Severe hostile reactions occurred in 26% of sufferers who obtained TUKYSA. Severe hostile reactions in ≥2% of sufferers who obtained TUKYSA have been diarrhea (4%), vomiting (2.5%), nausea (2%), belly ache (2%), and seizure (2%). Deadly hostile reactions occurred in 2% of sufferers who obtained TUKYSA together with sudden demise, sepsis, dehydration, and cardiogenic shock.

Adversarial reactions led to therapy discontinuation in 6% of sufferers who obtained TUKYSA; these occurring in ≥1% of sufferers have been hepatotoxicity (1.5%) and diarrhea (1%). Adversarial reactions led to dose discount in 21% of sufferers who obtained TUKYSA; these occurring in ≥2% of sufferers have been hepatotoxicity (8%) and diarrhea (6%).

The commonest hostile reactions in sufferers who obtained TUKYSA (≥20%) have been diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased urge for food, belly ache, headache, anemia, and rash.

Lab Abnormalities

In HER2CLIMB, Grade ≥3 laboratory abnormalities reported in ≥5% of sufferers who obtained TUKYSA have been: decreased phosphate, elevated ALT, decreased potassium, and elevated AST. The imply improve in serum creatinine was 32% inside the first 21 days of therapy with TUKYSA. The serum creatinine will increase endured all through therapy and have been reversible upon therapy completion. Contemplate different markers of renal perform if persistent elevations in serum creatinine are noticed.

Drug Interactions

• Robust CYP3A or Average CYP2C8 Inducers: Concomitant use might lower TUKYSA exercise. Keep away from concomitant use of TUKYSA.
• Robust or Average CYP2C8 Inhibitors: Concomitant use of TUKYSA with a robust CYP2C8 inhibitor might improve the chance of TUKYSA toxicity; keep away from concomitant use. Improve monitoring for TUKYSA toxicity with average CYP2C8 inhibitors.
• CYP3A Substrates: Concomitant use might improve the toxicity related to a CYP3A substrate. Keep away from concomitant use of TUKYSA the place minimal focus adjustments might result in critical or life-threatening toxicities. If concomitant use is unavoidable, lower the CYP3A substrate dosage.
• P-gp Substrates: Concomitant use might improve the toxicity related to a P-gp substrate. Contemplate decreasing the dosage of P-gp substrates the place minimal focus adjustments might result in critical or life-threatening toxicity.

Use in Particular Populations

• Lactation: Advise ladies to not breastfeed whereas taking TUKYSA and for no less than 1 week after the final dose.
• Renal Impairment: Use of TUKYSA together with capecitabine and trastuzumab will not be advisable in sufferers with extreme renal impairment (CLcr < 30 mL/min), as a result of capecitabine is contraindicated in sufferers with extreme renal impairment.
• Hepatic Impairment: Cut back the dose of TUKYSA for sufferers with extreme (Baby-Pugh C) hepatic impairment.

For extra info, please see the total Prescribing Data for TUKYSA right here.

About Seagen

Seagen is a worldwide biotechnology firm that discovers, develops and commercializes transformative most cancers medicines to make a significant distinction in folks’s lives. Seagen is headquartered within the Seattle, Washington space, and has places in California, Canada, Switzerland and the European Union. For extra info on the corporate’s marketed merchandise and strong pipeline, go to www.seagen.com and observe @SeagenGlobal on Twitter.

Ahead-Trying Statements

Sure of the statements made on this press launch are ahead trying, equivalent to these, amongst others, referring to the deliberate submission of a supplemental New Drug Utility to the FDA underneath the FDA’s Accelerated Approval Program, discussions with world well being authorities, the therapeutic potential of TUKYSA, its attainable efficacy, security and therapeutic makes use of, and the TUKYSA improvement program. Precise outcomes or developments might differ materially from these projected or implied in these forward-looking statements. Elements that will trigger such a distinction embrace the chance that the information from the MOUNTAINEER trial will not be ample to assist accelerated approval or enlargement of the labeled indications of use for TUKYSA within the U.S; the potential of impediments or delays within the submission of a supplemental New Drug Utility to the FDA; the chance of hostile occasions, together with the potential for newly-emerging security alerts; delays, setbacks or failures in scientific improvement and regulatory actions for a wide range of causes, together with the problem and uncertainty of pharmaceutical product improvement, hostile regulatory motion, attainable required modifications to scientific trials, failure to correctly conduct or handle scientific trials and failure of scientific outcomes to assist continued improvement or regulatory approvals. Extra details about the dangers and uncertainties confronted by Seagen is contained underneath the caption “Danger Elements” included within the firm’s Quarterly Report on Kind 10-Q for the quarter ended March 31, 2022, and subsequent periodic reviews, filed with the Securities and Alternate Fee. Seagen disclaims any intention or obligation to replace or revise any forward-looking statements, whether or not because of new info, future occasions or in any other case, besides as required by legislation.

____________________________

¹ American Most cancers Society Journal: World Most cancers Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Nations. https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21660. Accessed June 2022.

² American Most cancers Society: Key Statistics for Colorectal Most cancers-2022. https://www.most cancers.org/most cancers/colon-rectal-cancer/about/key-statistics.html. Accessed March 2022.

³ Wang J., et al. Metastatic patterns and survival outcomes in sufferers with stage IV colon most cancers: A population-based evaluation. Most cancers Med. 2020 Jan; 9(1): 361–373.

⁴ Takegawa N and Yonesaka Ok (2017). HER2 as an rising oncotarget for colorectal most cancers therapy after failure of anti-epidermal progress issue receptor remedy. Clin Colorectal Most cancers 16: 247-51.

⁵ Valtorta E., et al. Evaluation of a HER2 scoring system for colorectal most cancers: outcomes from a validation research. Mod Pathol 28: 1481-91 2015.

Contacts

For Media
David Caouette

Vice President, Company Communications

(310) 430-3476

[email protected]

For Buyers
Peggy Pinkston

Senior Vice President, Investor Relations

(425) 527-4160

[email protected]