Pfizer Unveils First Clinical Data of Two Novel ADCs Combined with Keytruda at ASCO 2025; Enzalutamide Shows Over 65% 5-Year OS Rate in Prostate Cancer

The 2025 ASCO Conference is in full swing, with Pfizer bringingMore than 60 itemsHeavyweight Clinical Research Results, Including15 Oral and Rapid Oral Reports，Indications cover breast cancer, genitourinary system cancers, hematological cancers, thoracic cancers, and colorectal cancer.

This article will select some for specific introduction, for readers' reference.Due toWenDue to limited space, it is difficult to include all important research results. Welcome to use the Insight database for reference (Long press the QR code at the end of the article).Free TrialOh~).

5 Annual OS Rate Reaches 66%

Enzalutamide Prostate Cancer Phase III Data Update

Pfizer and AstellasThe headline report format presented enzalutamide combined with androgen deprivation therapy at the ASCO conference.（ADT）Treatment of Metastatic Prostate Cancer（mHSPC）Phase IIIARCHES StudyFive-Year Follow-Up Overall Survival（OS）Data。

In the ARCHES study,1150 subjectsRandomly assigned 1:1 to receive either enzalutamide + ADT or placebo + ADT. The results showed,Compared with placebo + ADT, subjects treated with enzalutamide + ADT obtained OS benefits.The risk of death was reduced by 30%.。In patients with high-volume disease, the median OS was extended by 36 months, and data for other subgroups are shown in the figure below.

Source: ASCO Official Website

The incidence of adverse events during the five-year follow-up treatment was consistent with the previous ARCHES analysis results, and no new safety signals were identified.

In addition, Pfizer also announced at the conferenceBudenzalumide+Testosterone suppression therapy is used for mHSPC Phase IIIEight-Year Data from the ENZAMET Study. The results show,The median OS in the enzalutamide group was 8.0 years., the non-steroidal anti-androgen (NSAA) group was 5.8 years. The OS at 96 months was 50% in the enzalutamide group and 40% in the NSAA group; progression-free survival (PFS) was also better in the enzalutamide group compared to the NSAA group.（HR：0.49；95% CI，0.42-0.57）。

ITGB6 ADC、PDL1 ADC 

First Publication of Combined K Drug Clinical Data

At this year's ASCO conference, Pfizer made its first appearance.Showed2 Innovative ADCs and Pembrolizumab(K Drug)Phase I Clinical Data for Combined Treatment of Thoracic Cancer：ITGB6 ADC Sigvotatug Vedotin (SV) for the Treatment of Lung Cancer and Head and Neck CancerSGNB6A-001 Study；PDL1 ADC PF-08046054 for the treatment of head and neck cancerC5851001 Study。

   Sigvotatug vedotin

SGNB6A-001 is an open-label, multi-center, dose-escalation and dose-expansion Phase I clinical trial designed to evaluate the safety and pharmacokinetics of SV.（PK）And antitumor activity.Cohort C evaluates the safety of SV + pembrolizumab (P) in patients with advanced solid tumors; Cohort D is currently recruiting patients to evaluate SV + P in treatment-naïve locally advanced, unresectable, or metastatic NSCLC and squamous cell carcinoma of the head and neck.（HNSCC）Efficacy in patients. The results of this report come from Cohorts C and D.

As of November 26, 2024, a total of 31 subjects in Cohorts C and D had received ≥1 dose of SV+P treatment.(19 cases of NSCLC, 11 cases of HNSCC, and 1 case of esophageal cancer)；The median follow-up period was 2.9 months., 26 subjects are still receiving treatment. The median age of the patients is 65 years.(34-80 years old), 61% were male, and 52% had an ECOG PS score of 0. Among the NSCLC patients, 12 cases (63%) were non-squamous cell carcinoma, and 11 cases（58%）For patients with PD-L1 TPS≥1. The PD-L1 CPS score for all HNSCC patients is ≥1.

The results showed that in 7 evaluable patients with TPS≥1 NSCLC, it was observed that1 confirmed CR, 1 confirmed PR, and 2 unconfirmed PRs(ORR 57%; cORR 29%). Among the 8 evaluable patients with 1L HNSCC, it was observed that2 cases of cCR and 1 case of cPR（cORR 37.5%）。

In terms of safety, treatment-related adverse events of any grade and ≥3 grade（TEAE）The incidence rates were 87% and 35%, respectively, with the most common TEAEs shown in the table below. The incidence rates of immune-mediated TEAEs of any grade and ≥grade 3 were 61% and 10%, respectively. Three patients (9.7%)Pneumonia/interstitial lung disease occurred, with no ≥Grade 3 events. Two patients (6%)Discontinuation of treatment due to renal TEAE; another 3 patients discontinued treatment(1 case of disease progression, 2 cases withdrew informed consent). No treatment-related deaths occurred.

Source: ASCO Official Website

   PF-08046054

C5851001 includes a Phase I safety lead-in cohort (D), recruiting untreated R/M HNSCC patients with PD-L1 CPS ≥1 who have not received prior PD-1/PD-L1 monoclonal antibody therapy. The treatment cycle is 21 days.The first group of patients received 1.25 mg/kg of PF-08046054 on Day 1 and Day 8. After safety was demonstrated, the dose for the second group of patients was adjusted to 1.5 mg/kg. All patients received 200 mg of K drug every 3 weeks.

World's First KAT6 Inhibitor

About to Launch Phase III Clinical Trials

What Pfizer announced at the ASCO conference this time isFirst-in-Class KAT6 Inhibitor PF-07248144: Phase I Updated Clinical Data for ER+/HER2- Metastatic Breast Cancer。

As of October 11, 2024, a total of 107 patients who had previously received CDK4/6 inhibitors and endocrine therapy were administered the recommended expansion dose.（RDE）Treatment, where 35 patients received 5mg PF-07248144 monotherapy and 43 patients received 5mg PF-07248144+Fulvestrant（FUL）Combined therapy: 29 patients received 1mg PF-07248144 + FUL combined therapy, with a follow-up of at least 6 months.

Source: Insight Database

The results showed,In combination therapy, the most common TRAE in the 5mg and 1mg dose groups was dysgeusia, with incidence rates of 83.7% and 89.7%, respectively. The most common≥Grade 3 TRAEFor Neutropenia（G3：39.5% vs 20.7%；G4：7.0% vs 0.0%）Neutropenia is reversible and can be controlled by dose adjustment. No febrile neutropenia was observed. The safety of 5mg monotherapy is consistent with the safety of the 5mg combination therapy group.No pneumonia events were reported.

In terms of efficacy, the ORR for the 5mg dose combined with FUL group and the 1mg dose group were respectively37.2% and 24.1%`, Median Duration of Relief`（mDOR）Respectively15.8 months and 4.6 months, The clinical benefit rates were respectively55.8% and 37.9%, mPFS were respectively10.7 months and 3.6 months。

In summary, based on the above data，5 mg QD PF-07248144 was identified as the optimal dose for use in combination with FUL., with acceptable safety and encouraging efficacy. A pivotal Phase III clinical trial is planned to address the significant unmet medical need in ER+/HER2- mBC patients who progress after CDK4/6i combined with ET treatment.

Cover Source:Insight Database Mapping

Disclaimer:This article is for information sharing only, and does not represent the position or viewpoint of Insight. It does not recommend or introduce any treatment plans. If necessary, please consult and contact正规医疗机构.

Editor: Crescent

PR Article Coordination: WeChat insightxb