After six months of additional follow-up, clinical benefit rate (63%), overall response rate (41.9%), median progression-free survival (11.2 months), and safety profile of vepdegestrant in combination with palbociclib were consistent with data previously reported at SABCS in December 2023

经过6个月的额外随访，vepdegestrant联合palbociclib的临床获益率（63%）、总有效率（41.9%）、中位无进展生存期（11.2个月）和安全性与之前在2023年12月SABC报告的数据一致

At the recommended Phase 3 dose of 200 mg vepdegestrant in combination with palbociclib, patients achieved a median progression-free survival of 13.9 months (95% CI: 8.1-NR)

在推荐的3期剂量200 mg vepdegestrant联合palbociclib时，患者的中位无进展生存期为13.9个月（95%置信区间：8.1-NR）

Across all vepdegestrant dose groups, circulating tumor DNA analyses showed marked reduction in tumor fraction after one treatment cycle, regardless of ESR1 gene mutation status; at the 200 mg vepdegestrant dose, robust on-treatment decreases in mutant ESR1 circulating tumor DNA were sustained through multiple treatment cycles.

在所有vepdegestrant剂量组中，循环肿瘤DNA分析显示，无论ESR1基因突变状态如何，在一个治疗周期后，肿瘤分数均显着降低；在200 mg vepdegestrant剂量下，突变的ESR1循环肿瘤DNA在治疗期间的强劲下降通过多个治疗周期得以维持。

NEW HAVEN, Conn. and NEW YORK, May 16, 2024 (GLOBE NEWSWIRE) -- Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) today announced updated clinical data from a Phase 1b combination cohort evaluating vepdegestrant, an investigational oral PROteolysis TArgeting Chimera (PROTAC®) estrogen receptor (ER) degrader, in combination with palbociclib (IBRANCE®).

康涅狄格州纽黑文和纽约，2024年5月16日（环球通讯社）--Arvinas，Inc.（纳斯达克：ARVN）和辉瑞公司（纽约证券交易所：PFE）今天宣布了1b期联合队列评估vepdegestrant的最新临床数据，vepdegestrant是一种研究性口服蛋白水解靶向嵌合体（PROTAC®）雌激素受体（ER）降解剂，与palbociclib（IBRANCE®）联合使用。

After six months of additional follow-up, these data are consistent with data presented at the San Antonio Breast Cancer Symposium (SABCS) in December 2023, and show that vepdegestrant plus palbociclib continue to demonstrate encouraging clinical activity in heavily pre-treated patients with a median of four lines of prior therapy with locally advanced or metastatic ER positive (ER+)/human epidermal growth factor 2 (HER2) negative (ER+/HER2-) breast cancer.

经过六个月的额外随访，这些数据与2023年12月圣安东尼奥乳腺癌研讨会（SABCS）上提供的数据一致，并显示vepdegestrant加palbociclib在重度预处理患者中继续表现出令人鼓舞的临床活性，中位数为四行先前治疗的局部晚期或转移性ER阳性（ER+）/人表皮生长因子2（HER2）阴性（ER+/HER2-）乳腺癌。

These updated data were presented at the 2024 European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress..

这些最新数据在2024年欧洲医学肿瘤学会（ESMO）乳腺癌年会上发表。。

“We're encouraged by the clinical activity and safety profile observed with vepdegestrant in combination with palbociclib in patients being treated for advanced ER+/HER2- breast cancer,” said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. “The median progression-free survival and duration of response data suggest a promising therapeutic benefit for these patients regardless of ESR1 mutation status.”.

Arvinas首席医学官诺亚·伯克维茨（NoahBerkowitz）医学博士说：“我们对vepdegestrant联合palbociclib治疗晚期ER+/HER2乳腺癌的临床活性和安全性感到鼓舞。“中位无进展生存期和反应持续时间数据表明，无论ESR1突变状态如何，这些患者都有希望获得治疗益处。”。

Vepdegestrant is an investigational PROTAC ER degrader designed to harness the body’s natural protein disposal system to specifically target and degrade the estrogen receptor. Vepdegestrant is being co-developed by Arvinas and Pfizer and is being evaluated as a monotherapy in the second-line setting in the ongoing Phase 3 VERITAC-2 trial and in the first-line setting in combination with palbociclib in the ongoing study lead-in cohort of the Phase 3 VERITAC-3 trial..

Vepdegestrant是一种研究性的蛋白质降解剂，旨在利用人体的天然蛋白质处理系统来特异性靶向和降解雌激素受体。Vepdegestrant由Arvinas和Pfizer共同开发，正在进行的3期VERITAC-2试验的二线治疗中作为单一疗法进行评估，并在正在进行的3期VERITAC-3试验的研究导入队列中与palbociclib联合作为一线治疗。。

“Pfizer is focused on advancing the next generation of treatment breakthroughs for people with breast cancer,” said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. “With vepdegestrant, we hope to establish a new standard-of-care endocrine therapy backbone for patients with ER+/HER2- breast cancer, and the data shared at ESMO Breast Cancer continue to reinforce its potential.”.

辉瑞公司肿瘤首席开发官罗杰·丹西医学博士说：“辉瑞公司致力于推动乳腺癌患者的下一代治疗突破。”。“通过vepdegestrant，我们希望为ER+/HER2乳腺癌患者建立一个新的内分泌治疗标准，ESMO乳腺癌共享的数据继续增强其潜力。”。

“This study evaluating vepdegestrant in combination with palbociclib among heavily pre-treated patients with advanced ER+/HER2- metastatic breast cancer is consistent with the clinical activity, safety, and tolerability outcomes reported at SABCS 2023,” said Erika Hamilton, M.D., Director Breast Cancer Research and Executive Chair, Breast Cancer Research Executive Committee, Sarah Cannon Research Institute in Nashville, Tennessee, and a lead investigator in the vepdegestrant clinical program and presenting author on the data presentation at ESMO Breast Cancer.

“这项评估vepdegestrant联合palbociclib治疗晚期ER+/HER2转移性乳腺癌患者的研究与SABCS 2023报告的临床活性，安全性和耐受性结果一致，”Erika Hamilton医学博士说，她是田纳西州纳什维尔市Sarah Cannon研究所乳腺癌研究执行委员会主任兼执行主席，也是vepdegestrant临床计划的首席研究员，也是ESMO乳腺癌数据报告的作者。

“The data show promise that vepdegestrant could be a potential addition to current treatment options for this patient population, where there are significant unmet needs.”.

“数据显示，vepdegestrant有望成为该患者群体当前治疗选择的潜在补充，因为该患者群体存在大量未满足的需求。”。

Vepdegestrant + Palbociclib Phase 1b Study

Vepdegestrant+Palbociclib 1b期研究

The Phase 1b cohort of the ARV-471-mBC-101 study (NCT04072952) is designed to assess the safety, tolerability, and anti-tumor activity of vepdegestrant in combination with palbociclib among 46 patients with heavily pre-treated locally advanced or metastatic ER+/HER2- breast cancer. Patients in the study received a median of four prior therapies (median of three in the metastatic setting); 87% were previously treated with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor; 80% were previously treated with fulvestrant; and 78% were previously treated with chemotherapy, including 48% in the metastatic setting..

ARV-471-mBC-101研究（NCT04072952）的1b期队列旨在评估vepdegestrant联合palbociclib治疗46例严重预处理的局部晚期或转移性ER+/HER2患者的安全性，耐受性和抗肿瘤活性-乳腺癌。该研究中的患者接受了四种先前治疗的中位数（转移性中位数为三）；87%以前用细胞周期蛋白依赖性激酶4和6（CDK4/6）抑制剂治疗；80%以前用氟维司群治疗过；78%以前接受过化疗，其中48%在转移性环境中。。

Patients were treated once daily with oral doses of vepdegestrant at 180 mg (n=2), the recommended Phase 3 dose (RP3D) of 200 mg (n=21), 400 mg (n=3) or 500 mg (n=20), plus 125 mg of palbociclib given orally once daily for 21 days, followed by seven days off treatment in 28-day cycles. Initial data were presented at SABCS 2023 based on a data cutoff of June 6, 2023..

患者每天服用一次口服剂量为180 mg（n=2）的vepdegestrant，推荐的3期剂量（RP3D）为200 mg（n=21），400 mg（n=3）或500 mg（n=20），加上125 mg palbociclib，每天口服一次，持续21天，然后在28天的周期中休息7天。初始数据是根据2023年6月6日的数据截止日期在SABCS 2023上提供的。。

After six months of additional follow-up with a data cutoff of December 18, 2023, updated data from the study continue to demonstrate an encouraging clinical benefit rate, objective response rate and progression-free survival, and a consistent safety profile as previously reported at SABCS 2023.

经过六个月的额外随访，数据截止日期为2023年12月18日，该研究的最新数据继续显示出令人鼓舞的临床获益率，客观缓解率和无进展生存率，以及先前在SABCS 2023上报道的一致的安全性。

Data presented at the 2024 ESMO Breast Cancer Annual Congress:

2024年ESMO乳腺癌年会上提供的数据：

Clinical Benefit Rate (CBR):

临床受益率（CBR）：

CBR, defined as the rate of confirmed complete response, partial response, or stable disease ≥24 weeks across all dose levels (n = 46) was 63% (95% CI: 47.5 - 76.8), with a CBR of 72% in patients with mutant ESR1 (n=29; 95% CI: 52.8 - 87.3) and a CBR of 53% in patients with wild-type ESR1 (n=15; 95% CI: 26.6 – 78.7)..

CBR定义为在所有剂量水平（n=46）中≥24周确诊的完全缓解，部分缓解或稳定疾病的发生率为63%（95%CI:47.5-76.8），突变型ESR1患者的CBR为72%（n=29；95%CI:52.8-87.3），野生型ESR1患者的CBR为53%（n=15；95%CI:26.6-78.7）。。

CBR in patients dosed at the RP3D of 200 mg (n=21) was 67% (95% CI: 43.0 - 85.4) with a CBR of 79% in patients with mutant ESR1 (n=14; 95% CI: 49.2 - 95.3) and a CBR of 43% in patients with wild-type ESR1 (n=7; 95% CI: 9.9 - 81.6)

RP3D剂量为200 mg（n=21）的患者CBR为67%（95%CI:43.0-85.4），突变型ESR1患者CBR为79%（n=14；95%CI:49.2-95.3），野生型ESR1患者CBR为43%（n=7；95%CI:9.9-81.6）

Objective Response Rate (ORR) and Duration of Response (DOR):

客观缓解率（ORR）和缓解持续时间（DOR）：

The ORR in evaluable patients with measurable disease at baseline (n=31) was 42% (95% CI: 24.5 - 60.9) with a median DOR in 13 responders of 14.6 months (95% CI: 9.5 – not reached). At the RP3D of 200 mg (n=15), the ORR was 53% (95% CI: 25.6 – 78.7).

基线时可测量疾病的可评估患者（n=31）的ORR为42%（95%CI:24.5-60.9），13名应答者的中位DOR为14.6个月（95%CI:9.5-未达到）。在RP3D为200 mg（n=15）时，ORR为53%（95%CI:25.6-78.7）。

ORR in patients with mutant ESR1 (n=17): 47% (95% CI: 23.0 - 72.2).

突变ESR1患者的ORR（n=17）：47%（95%CI:23.0-72.2）。

ORR at the RP3D of 200 mg (n=10): 60% (95% CI: 26.2 - 87.8).

RP3D为200mg（n=10）时的ORR为60%（95%CI:26.2-87.8）。

ORR in patients with wild-type ESR1 (n=12): 42% (95% CI: 15.2 - 72.3).

野生型ESR1患者的ORR（n=12）：42%（95%CI:15.2-72.3）。

ORR at the RP3D of 200 mg (n=5): 40% (95% CI: 5.3 - 85.3).

RP3D为200mg时的ORR（n=5）:40%（95%CI:5.3-85.3）。

Progression-free Survival (PFS):

无进展生存期（PFS）：

Median PFS (mPFS) based on 27 (59%) events across all dose levels was 11.2 months (95% CI: 8.2 – 16.5) with a mPFS of 13.7 months (95% CI: 8.2 - NR) in patients with ESR1 mutation (n=29) and mPFS of 11.1 months (95% CI: 2.8 - 19.3) in patients with wild-type ESR1 (n=15).

ESR1突变患者（n=29）和野生型ESR1患者（n=15）的中位PFS（mPFS）分别为11.2个月（95%CI:8.2-16.5）和13.7个月（95%CI:8.2-NR）。

mPFS in patients dosed at the RP3D of 200 mg (n=21) based on 12 events (57%) was 13.9 months (95% CI: 8.1 - NR) with a mPFS of 13.9 months (95% CI: 8.1 - NR) in patients with ESR1 mutation (n=14) and mPFS of 11.2 months (95% CI: 1.8 - NR) in patients with wild-type ESR1 (n=7).

根据12个事件（57%），RP3D剂量为200 mg（n=21）的患者的mPFS为13.9个月（95%CI:8.1-NR），ESR1突变患者（n=14）的mPFS为13.9个月（95%CI:8.1-NR），野生型ESR1患者（n=7）的mPFS为11.2个月（95%CI:1.8-NR）。

Circulating Tumor DNA (ctDNA):

循环肿瘤DNA（ctDNA）：

Exploratory ctDNA analyses found marked reduction (median change, −98.9%) in tumor fraction after one treatment cycle (all dose groups) regardless of ESR1 mutant status and robust on-treatment decreases in mutant ESR1 ctDNA levels sustained through cycle 7 (evaluated in patients in 200 mg dose cohort), as presented in the poster session..

探索性ctDNA分析发现，无论ESR1突变体状态如何，在一个治疗周期（所有剂量组）后，肿瘤分数均显着降低（中位数变化，-98.9%），并且在第7周期持续的突变ESR1 ctDNA水平（在200 mg剂量组的患者中进行评估）在治疗期间下降强劲，如海报会议所示。。

Safety Profile:

安全简介：

The safety profile of vepdegestrant plus palbociclib was consistent with what was previously reported with Grade 3/4 treatment-related adverse events (TRAEs) ≥10% of neutropenia (91%) and decreased white blood cell count (15%); no grade 5 TRAEs or febrile neutropenia were reported.

vepdegestrant加palbociclib的安全性与先前报道的3/4级治疗相关不良事件（TRAEs）≥10%的中性粒细胞减少症（91%）和白细胞计数降低（15%）一致；没有报告5级TRAE或发热性中性粒细胞减少症。

The majority of Grade 4 neutropenia events occurred in the first cycle of treatment and occurrences of Grade 3/4 neutropenia decreased following palbociclib dose reductions as described in the prescribing label.

大多数4级中性粒细胞减少症事件发生在治疗的第一个周期，并且如处方标签中所述，palbociclib剂量减少后3/4级中性粒细胞减少症的发生率降低。

The safety profile of vepdegestrant in combination with palbociclib was otherwise consistent with the profile of palbociclib and what has been observed in other clinical trials for vepdegestrant. Three of 46 patients discontinued palbociclib due to neutropenia including one out of 21 patients treated with the RP3D of vepdegestrant (200 mg) plus palbociclib 125 mg..

vepdegestrant联合palbociclib的安全性与palbociclib的特征以及在vepdegestrant的其他临床试验中观察到的一致。46名患者中有3名因中性粒细胞减少而停用了palbociclib，其中21名患者中有1名接受了vepdegestrant（200 mg）的RP3D加palbociclib 125 mg治疗。。

About Vepdegestrant

关于Web

Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer..

Vepdegestrant是一种研究性口服生物可利用的PROTAC蛋白降解剂，旨在特异性靶向和降解雌激素受体（ER），用于治疗ER阳性（ER+）/人表皮生长因子受体2（HER2）阴性（ER+/HER2-）乳腺癌患者。Vepdegestrant正在开发作为一种潜在的单一疗法，并作为ER+/HER2转移性乳腺癌多种治疗环境中联合治疗的一部分。。

In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits.

2021年7月，Arvinas宣布与辉瑞公司进行全球合作，共同开发和共同商业化vepdegestrant；Arvinas和辉瑞将分担全球开发成本、商业化费用和利润。

The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.

美国食品和药物管理局（FDA）已将vepdegestrant快速通道指定为单一疗法，用于治疗先前接受内分泌治疗的ER+/HER2局部晚期或转移性乳腺癌。

About IBRANCE® (palbociclib) 125 mg tablets and capsules

关于IBRANCE®（palbociclib）125毫克片剂和胶囊

IBRANCE is an oral inhibitor of CDKs 4 and 6,1 which are key regulators of the cell cycle that trigger cellular progression.2,3 In the U.S., IBRANCE is a prescription medicine indicated for the treatment of adults with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as the first hormonal based therapy; or with fulvestrant in people with disease progression following hormonal therapy..

IBRANCE是CDKs 4和6,1的口服抑制剂，CDKs 4和6,1是触发细胞进展的细胞周期的关键调节剂。2,3在美国，IBRANCE是一种处方药，用于治疗HR+，HER2晚期或转移性乳腺癌，与芳香化酶抑制剂联合作为第一种基于激素的疗法；或在激素治疗后疾病进展的患者中使用氟维司群。。

The full U.S. Prescribing Information for the IBRANCE tablets and the IBRANCE capsules can be found here and here.

关于IBRANCE片剂和IBRANCE胶囊的完整美国处方信息可以在这里和这里找到。

IMPORTANT IBRANCE®(palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

来自美国处方信息的重要IBRANCE®（palbociclib）安全信息

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant.

中性粒细胞减少症是PALOMA-2（80%）和PALOMA-3（83%）中最常报告的不良反应。在PALOMA-2中，接受IBRANCE加来曲唑治疗的患者报告3级（56%）或4级（10%）中性粒细胞计数减少。在PALOMA-3中，接受IBRANCE加氟维司群治疗的患者报告3级（55%）或4级（11%）中性粒细胞计数减少。

Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever..

据报道，在PALOMA-2和PALOMA-3暴露于IBRANCE的患者中，有1.8%患有发热性中性粒细胞减少症。在PALOMA-3中观察到一例因中性粒细胞减少性败血症而死亡。通知患者立即报告任何发烧。。

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

在开始IBRANCE之前，在每个周期开始时，在前2个周期的第15天以及临床指示时监测全血细胞计数。对于发生3级或4级中性粒细胞减少症的患者，建议中断剂量，减少剂量或延迟开始治疗周期。

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with CDK4/6 inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical trials (PALOMA-1, PALOMA-2, PALOMA-3), 1.0% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported.

使用CDK4/6抑制剂（包括IBRANCE）联合内分泌治疗的患者可能会发生严重，危及生命或致命的间质性肺病（ILD）和/或肺炎。在临床试验（PALOMA-1，PALOMA-2，PALOMA-3）中，1.0%的IBRANCE治疗患者患有任何级别的ILD/肺炎，0.1%患有3级或4级，没有致命病例报告。

Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported..

在上市后的环境中还观察到了其他ILD/肺炎病例，并报告了死亡人数。。

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g., hypoxia, cough, dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have developed pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis..

监测患者是否有指示ILD/肺炎的肺部症状（例如缺氧，咳嗽，呼吸困难）。对于有新的或恶化的呼吸道症状并怀疑患有肺炎的患者，立即中断IBRANCE并对患者进行评估。严重ILD或肺炎患者永久停用IBRANCE。。

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients to consider sperm preservation before taking IBRANCE.

根据作用机制，IBRANCE可引起胎儿伤害。建议有生殖潜力的女性在IBRANCE治疗期间以及最后一剂后至少3周内使用有效的避孕措施。IBRANCE可能会损害男性的生育能力，并有可能引起遗传毒性。建议男性患者在服用IBRANCE之前考虑保存精子。

Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants..

建议有生殖潜力的女性伴侣的男性患者在IBRANCE治疗期间和最后一剂后3个月内使用有效的避孕措施。建议女性告知其医疗保健提供者已知或疑似怀孕。建议女性在IBRANCE治疗期间和最后一次给药后3周内不要母乳喂养，因为哺乳期婴儿可能会出现严重的不良反应。。

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%)..

PALOMA-2报告的IBRANCE加来曲唑与安慰剂加来曲唑最常见的不良反应（≥10%）是中性粒细胞减少症（80%比6%）、感染（60%比42%）、白细胞减少症（39%比2%）、疲劳（37%比28%）、恶心（35%比26%）、脱发（33%比16%）、口腔炎（30%比14%）、腹泻（26%比19%）、贫血（24%比9%）、皮疹（18%比12%）、虚弱（17%比12%）、血小板减少症（16%比1%）、呕吐（16%比17%）、食欲下降（15%比9%）、皮肤干燥（12%比6），发热（12%比9%）和味觉障碍（10%比5%）。。

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

对于IBRANCE加来曲唑与安慰剂加来曲唑，PALOMA-2中最常报告的≥3级不良反应（≥5%）是中性粒细胞减少症（66%比2%），白细胞减少症（25%比0%），感染（7%比3%）和贫血（5%比2%）。

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%)..

在PALOMA-2中，IBRANCE加来曲唑与安慰剂加来曲唑相比，任何级别的实验室异常均为白细胞减少（97%比25%），中性粒细胞减少（95%比20%），贫血（78%比42%），血小板减少（63%比14%），天冬氨酸转氨酶增加（52%比34%），丙氨酸转氨酶增加（43%比30%）。。

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%)..

PALOMA-3报告的IBRANCE加氟维司群与安慰剂加氟维司群最常见的不良反应（≥10%）是中性粒细胞减少症（83%比4%），白细胞减少症（53%比5%），感染（47%比31%），疲劳（41%比29%），恶心（34%比28%），贫血（30%比13%），口腔炎（28%比13%），腹泻（24%比19%），血小板减少症（23%比0%），呕吐（19%比15%），脱发（18%比6%），皮疹（17%比6%），食欲下降（16%比8%）和发热（13%比5%）。。

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

对于IBRANCE加氟维司群与安慰剂加氟维司群，PALOMA-3中最常报告的≥3级不良反应（≥5%）是中性粒细胞减少症（66%比1%）和白细胞减少症（31%比2%）。

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%)..

在PALOMA-3中，IBRANCE加氟维司群与安慰剂加氟维司群发生的任何级别的实验室异常均为白细胞减少（99%比26%），中性粒细胞减少（96%比14%），贫血（78%比40%），血小板减少（62%比10%），天冬氨酸转氨酶增加（43%比48%），丙氨酸转氨酶增加（36%比34%）。。

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor.

避免同时使用强CYP3A抑制剂。如果患者必须服用强效CYP3A抑制剂，则将IBRANCE剂量降低至75 mg。如果停用强效抑制剂，则将IBRANCE剂量（抑制剂的3-5个半衰期后）增加至强效CYP3A抑制剂开始前使用的剂量。

Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure..

葡萄柚或葡萄柚汁可能会增加IBRANCE的血浆浓度，应避免使用。避免同时使用强CYP3A诱导剂。可能需要减少治疗指数较窄的敏感CYP3A底物的剂量，因为IBRANCE可能会增加其暴露量。。

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.

对于严重肝功能损害（Child-Pugh C级）的患者，推荐的IBRANCE剂量为75 mg。尚未在需要血液透析的患者中研究IBRANCE的药代动力学。

About Arvinas

Arvinas

Arvinas is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases through the discovery, development, and commercialization of therapies that degrade disease-causing proteins. Arvinas uses its proprietary PROTAC® Discovery Engine platform to engineer proteolysis targeting chimeras, or PROTAC® targeted protein degraders, that are designed to harness the body’s own natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins.

Arvinas是一家临床阶段生物技术公司，致力于通过发现、开发和商业化降解致病蛋白的疗法来改善患有衰弱和威胁生命的疾病的患者的生活。Arvinas使用其专有的PROTAC®发现引擎平台来设计针对嵌合体的蛋白水解或针对PROTAC®的蛋白质降解剂，旨在利用人体自身的天然蛋白质处理系统选择性和有效地降解和去除致病蛋白质。

In addition to its robust preclinical pipeline of PROTAC protein degraders against validated and “undruggable” targets, the company has four investigational clinical-stage programs: vepdegestrant for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-766 and bavdegalutamide for the treatment of men with metastatic castration-resistant prostate cancer; and ARV-102 for the treatment of patients with neurodegenerative disorders.

除了针对经过验证和“不可治疗”的靶标的PROTAC蛋白降解剂的强大临床前管道外，该公司还有四个研究性临床阶段计划：用于治疗局部晚期或转移性ER+/HER2乳腺癌患者的vepdegestrant；ARV-766和bavdegalutamide用于治疗转移性去势抵抗性前列腺癌男性；和ARV-102用于治疗神经退行性疾病患者。

For more information, visit www.arvinas.com..

有关更多信息，请访问www.arvinas.com。。

About Pfizer Oncology

关于辉瑞肿瘤学

At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics.

在辉瑞肿瘤学，我们处于癌症护理新时代的前沿。我们业界领先的产品组合和广泛的渠道包括从多个角度攻击癌症的三个核心作用机制，包括小分子，抗体-药物偶联物（ADC）和双特异性抗体，包括其他免疫肿瘤学生物制剂。

We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives..

我们专注于为世界上一些最常见的癌症提供变革性治疗，包括乳腺癌，泌尿生殖系统癌症，血液肿瘤和包括肺癌在内的胸癌。在科学的推动下，我们致力于加速突破，帮助癌症患者过上更好、更长的生活。。

About Pfizer: Breakthroughs That Change Patients’ Lives

关于辉瑞：改变患者生活的突破

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines.

在辉瑞，我们运用科学和全球资源为人们带来治疗方法，延长并显着改善他们的生活。我们努力为包括创新药物和疫苗在内的保健产品的发现、开发和制造制定质量、安全和价值标准。

Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world.

辉瑞公司的同事们每天都在发达市场和新兴市场开展工作，促进健康、预防、治疗和治愈，挑战我们这个时代最可怕的疾病。作为世界首屈一指的创新生物制药公司之一，我们与医疗保健提供者、政府和当地社区合作，支持和扩大全球可靠、负担得起的医疗保健服务。

For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on X at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer..

175年来，我们一直致力于为所有依赖我们的人带来改变。我们经常在我们的网站www.pfizer.com上发布对投资者可能很重要的信息。此外，要了解更多信息，请访问我们的网站www.pfizer.com，并在X上关注我们，网址为@pfizer和@pfizer\u News，LinkedIn，YouTube，以及在Facebook上关注我们。。

Arvinas Forward-Looking Statements

Arvinas前瞻性声明

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding ; the potential, pending regulatory approval, for vepdegestrant to address an area of high unmet need; Arvinas’ and Pfizer’s plans with respect to, the timing and results of ongoing and planned clinical trials of vepdegestrant, as a monotherapy and in combination studies; and statements regarding potential therapeutic benefits of vepdegestrant.

本新闻稿包含1995年《私人证券诉讼改革法案》所指的前瞻性声明，涉及重大风险和不确定性，包括以下声明：；vepdegestrant在等待监管部门批准的情况下，有可能解决高度未满足需求的领域；Arvinas和辉瑞公司关于vepdegestrant正在进行和计划进行的临床试验的时间和结果的计划，作为单一疗法和联合研究；以及关于vepdegestrant潜在治疗益处的声明。

All statements, other than statements of historical facts, contained in this press release, including statements regarding Arvinas’ strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements.

本新闻稿中包含的除历史事实声明外的所有声明，包括有关Arvinas战略、未来运营、未来财务状况、未来收入、预计成本、前景、计划和管理目标的声明，均为前瞻性声明。

The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words..

“预期”，“相信”，“估计”，“期望”，“打算”，“可能”，“可能”，“计划”，“预测”，“项目”，“目标”，“潜在”，“将”，“会”，“可能”，“应该”，“继续”等词语以及类似的表达旨在识别前瞻性陈述，尽管并非所有前瞻性陈述都包含这些识别词。。

Arvinas may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on such forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements Arvinas makes as a result of various risks and uncertainties, including but not limited to: Arvinas’ and Pfizer Inc.’s (“Pfizer”) performance of the respective obligations with respect to Arvinas’ collaboration with Pfizer; whether Arvinas and Pfizer will be able to successfully conduct and complete clinical development for vepdegestrant; whether Arvinas and Pfizer, as appropriate, will be able to obtain marketing approval for and commercialize vepdegestrant on current timelines or at all; Arvinas’ ability to protect its intellectual property portfolio; whether Arvinas’ cash and cash equivalent resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; and other important factors discussed in the “Risk Factors” section of Arvinas’ Annual Report on Form 10-K for the year ended December 31, 2023 , its Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, and subsequent other reports on file with the U.S.

Arvinas可能无法实际实现这些前瞻性声明中披露的计划、意图或期望，您不应过度依赖这些前瞻性声明。由于各种风险和不确定性，实际结果或事件可能与Arvinas在前瞻性声明中披露的计划、意图和预期存在重大差异，包括但不限于：Arvinas和辉瑞公司（“辉瑞”）履行与Arvinas与辉瑞合作相关的各自义务；Arvinas和Pfizer是否能够成功进行和完成vepdegestrant的临床开发；Arvinas和Pfizer（视情况而定）是否能够在当前时间表上获得vepdegestrant的营销批准并将其商业化；Arvinas保护其知识产权组合的能力；Arvinas的现金和现金等价物资源是否足以满足其可预见和不可预见的运营费用和资本支出要求；以及Arvinas截至2023年12月31日的10-K表年度报告、截至2024年3月31日的10-Q表季度报告以及随后提交给美国的其他报告中“风险因素”部分讨论的其他重要因素。

Securities and Exchange Commission. The forward-looking statements contained in this press release reflect Arvinas’ current views with respect to future events, and Arvinas assumes no obligation to update any forward-looking statements, except as required by applicable law. These forward-looking statements should not be relied upon as representing Arvinas’ views as of any date subsequent to the date of this release..

证券交易委员会。本新闻稿中包含的前瞻性声明反映了Arvinas对未来事件的当前观点，除适用法律要求外，Arvinas没有义务更新任何前瞻性声明。这些前瞻性声明不应被视为代表Arvinas在本发布日期之后的任何日期的观点。。

Pfizer Disclosure Notice:

辉瑞披露通知：

The information contained in this release is as of May 16, 2024. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

本版本中包含的信息截至2024年5月16日。辉瑞没有义务因新信息或未来事件或发展而更新本版本中包含的前瞻性声明。

This release contains forward-looking information about vepdegestrant, IBRANCE® (palbociclib), a global collaboration between Pfizer and Arvinas to develop and commercialize vepdegestrant and Pfizer Oncology, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements.

本版本包含关于vepdegestrant，IBRANCE®（palbociclib）的前瞻性信息，这是辉瑞和Arvinas之间的全球合作，旨在开发和商业化vepdegestrant和辉瑞肿瘤学，包括它们的潜在益处，涉及重大风险和不确定性，可能导致实际结果与此类声明所表达或暗示的结果存在实质性差异。

Risks and uncertainties include, among other things, uncertainties regarding the commercial success of IBRANCE; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from the clinical studies; whether and when any applications may be filed in any jurisdictions for vepdegestrant for any potential indications or any other potential indications for IBRANCE; whether and when regulatory authorities may approve any potential applications that may be filed for vepdegestrant and/or IBRANCE in any jurisdictions, which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether such product will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availabi.

风险和不确定性包括IBRANCE商业成功的不确定性；研究和开发固有的不确定性，包括满足预期临床终点的能力，临床试验的开始和/或完成日期，监管提交日期，监管批准日期和/或发布日期，以及不利的新临床数据的可能性和现有临床数据的进一步分析；临床试验数据受到监管机构不同解释和评估的风险；监管机构是否会对临床研究的设计和结果感到满意；是否以及何时可以在任何司法管辖区为vepdegestrant提出任何潜在迹象或任何其他潜在迹象的申请；监管机构是否以及何时可以批准可能在任何司法管辖区向vepdegestrant和/或IBRANCE提交的任何潜在申请，这将取决于无数因素，包括确定产品的益处是否超过其已知风险，确定产品的功效，以及如果批准，该产品是否会取得商业成功；监管机构做出的影响标签、制造过程、安全和/或其他可能影响可用性的事项的决定。

A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S.

关于风险和不确定性的进一步描述，可以在辉瑞公司截至2023年12月31日的10-K财年年度报告和随后的10-Q表格报告中找到，包括标题为“风险因素”和“前瞻性信息和可能影响未来结果的因素”的部分，以及随后的8-K表格报告中找到，所有这些报告都提交给美国。

Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com..

证券交易委员会（sec），网址为www.sec.gov和www.pfizer.com。。

Arvinas Contacts

_其他组织者

Investor Contact:

投资者联系人：

Jeff Boyle

Jeff Boyle

347-247-5089

347-247-5089

Jeff.Boyle@arvinas.com

Jeff.Boyle@arvinas.com

Media Contact:

媒体联系人：

Kathleen Murphy

凯瑟琳·莫非

+1 (760) 622-3771

+1 (760) 622-3771

Kathleen.Murphy@arvinas.com

Kathleen.Murphy@arvinas.com

Pfizer Contacts

辉瑞联系人

Investor Contact:

投资者联系人：

+1 (212) 733-4848

+1 (212) 733-4848

IR@pfizer.com

IR@pfizer.com

Media Contact:

媒体联系人：

+1 (212) 733-1226

+1 (212) 733-1226

PfizerMediaRelations@pfizer.com

PfizerMediaRelations@pfizer.com

1 IBRANCE® (palbociclib) Prescribing Information. New York. NY: Pfizer Inc: September 2023.

1 IBRANCE®（palbociclib）处方信息。纽约：辉瑞公司：2023年9月。

2 Weinberg, RA. pRb and Control of the Cell Cycle Clock. In: Weinberg RA, ed. The Biology of Cancer. 2nd ed. New York, NY: Garland Science; 2014:275-329.

2温伯格，RA。pRb和细胞周期时钟的控制。发表于：Weinberg RA，ed。The Biology of Cancer。第二版。纽约，纽约：花环科学；2014:275-329。

3 Sotillo E, Grana X. Escape from Cellular Quiescence. In: Enders GH, ed. Cell Cycle Deregulation in Cancer. New York, NY: Humana Press; 2010:3-22.

3 Sotillo E，Grana X.逃离细胞静止。在：Enders GH，ed。癌症中的细胞周期失调。纽约，纽约：Humana出版社；2010:3-22。