On May 31, 2025 Mythic Therapeutics, a clinical-stage biotechnology company developing next-generation antibody-drug conjugate (ADC) therapies for the treatment of a wide range of cancers, reported updated data from its Phase 1 KisMET-01 study evaluating its investigational cMET-targeting ADC candidate, MYTX-011, in patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC), in a poster at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Mythic Therapeutics, MAY 31, 2025, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-presents-compelling-efficacy-data-from-its-phase-1-kismet-01-study-supporting-best-in-class-potential-of-novel-cmet-adc-mytx-011-in-non-small-cell-lung-cancer-asco-2025 [SID1234653549]). MYTX-011 is a novel ADC engineered with pH-dependent binding to more precisely deliver anti-tumor payload across a range of cMET expression levels, with the goal of reducing toxicity and expanding the number of patients who can benefit from ADC therapy.

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"We are highly encouraged by these early efficacy data demonstrating meaningful anti-tumor activity which underscore how our differentiated pH-dependent design may help unlock the full promise of ADCs to reshape cancer treatment and expand patient reach, regardless of histology and molecular subtype," said George Eliades, Ph.D., President and Chief Executive Officer at Mythic Therapeutics. "Together with a manageable tolerability profile, these findings support the potential of MYTX-011 to establish a new standard of care for pretreated NSCLC patients in second- and later-line settings, where effective treatment options remain extremely limited. We look forward to evaluating MYTX-011 in Part 2 of the study and plan to present updated expansion cohort data at an upcoming medical conference."

Data presented were from 66 patients treated at efficacious dose levels (≥4.0 mg/kg) administered once every three weeks (Q3W) in Part 1 of the dose escalation portion of the study. Patients had a median of three, and up to 10, prior lines of therapy with nearly half (45%) receiving prior taxane treatments. Preliminary results show:

Anti-tumor activity was consistent regardless of cMET expression levels, EGFR mutation status or prior taxane treatment.
In non-squamous, cMET+ tumors, the ORR was 39% in cMET high/intermediate (n=23) and 36% in cMET low tumors (n=11).
Responses were observed in patients with and without actionable genomic alterations, including a 50% ORR in patients with tumors containing both EGFR mutations and cMET high or intermediate expression.
Overall, responses were durable, with observed durations of up to 8.9 months and ongoing; the majority of patients with responses remain on treatment.
Disease control rate (DCR) was 80% at 12 weeks (n=24 of 30) and 52% at 24 weeks (n=14 of 27).
All four response-evaluable patients with squamous histology tumors and low cMET levels had clinical benefit; one partial response was observed and the three other patients had durable stable disease.
MTYX-011 demonstrated favorable pharmacokinetics (PK) and excellent stability. The overall safety profile of MYTX-011 was consistent with previously reported data, and no new safety signals were identified. The most common treatment-related adverse events (TRAEs) of any grade in 20% or more of patients included, blurred vision (47%), keratopathy (41%), keratitis (32%), nausea (29%), peripheral neuropathy (24%), fatigue (23%), and increased AST (21%). Grade 3 or higher TRAEs in 5% or more of patients included blurred vision (20%), keratopathy (18%), neutropenia (14%), and keratitis (11%). 11 of the 12 reports of neutropenia and 12 of the 16 cases of peripheral neuropathy occurred in patients treated at doses of 5.8 mg/kg or higher. Ocular AEs led to treatment discontinuation in four patients (6%), with three of the four patients receiving doses of 5.8 mg/kg or higher. Based on clinical data and favorable PK, a 5.0 mg/kg dose on a Q3W regimen with a 2-on, 1-off dose break schedule was selected as the recommended Phase 2 dose, which will be compared to a 4.0 mg/kg Q3W dose in Part 2 of the trial.

"The early data from the MYTX-011 study, showing compelling anti-tumor activity and durable responses in patients with lung cancer, together with a well-tolerated safety profile, are highly encouraging," said Rebecca Heist, M.D., MPH, Medical Oncologist, Massachusetts General Hospital, Cancer Center. "These findings suggest that MYTX-011 has the potential to become a promising new treatment option for a broad range of NSCLC patients, and we are eager to continue evaluating its efficacy and safety in the ongoing dose expansion phase of the study."

About KisMET-01

KisMET-01 (NCT05652868) is a multicenter, first-in-human Phase 1 study of MYTX-011 in patients with previously treated, locally advanced or metastatic NSCLC. The study is comprised of two parts: dose escalation (Part 1) in patients with NSCLC of any histology of cMET expression with cMET analyzed whenever tumor tissue is available, followed by dose expansion (Part 2) in cMET-positive (cMET+) patients selected by immunohistochemistry (Ventana SP44). cMET levels are defined as high (≥50% tumor cells with 3+ staining), intermediate (≥25% and <50% with 3+ staining), low (≥25% with 2+ staining, excluding high and intermediate), and ultra-low (≥75% excluding high, intermediate, and low).

About MYTX-011

MYTX-011 is an investigational cMET-targeting ADC, which leverages Mythic’s innovative FateControl technology. FateControl ADCs are pH engineered to unbind their target after internalization, intended to improve both tumor uptake and drug exposure for improved safety, tolerability and efficacy. MYTX-011 is currently being evaluated in the Phase 1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose escalation and dose expansion study enrolling patients with locally advanced, recurrent or metastatic NSCLC (NCT05652868).

On May 31, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that KEYTRUDA (pembrolizumab) plus Trodelvy (sacituzumab govitecan-hziy) reduced the risk of disease progression or death by 35% (HR=0.65, p<0.001) versus KEYTRUDA plus chemotherapy for the first-line treatment of patients with PD-L1+ (Combined Positive Score [CPS] ≥10) inoperable (unresectable) locally advanced or metastatic triple-negative breast cancer (TNBC), as determined by an FDA-approved test. KEYTRUDA, when given in combination with Gilead’s TROP2 antibody-drug conjugate (ADC) Trodelvy, resulted in a median progression-free survival (PFS) of 11.2 months versus 7.8 months when KEYTRUDA was given in combination with chemotherapy (Press release, Merck & Co, MAY 31, 2025, View Source [SID1234653548]). These data from the pivotal Phase 3 ASCENT-04/KEYNOTE-D19 study will be presented today as a late-breaking oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #LBA109) and were selected for the official ASCO (Free ASCO Whitepaper) Press Program.

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"These results have the potential to be an important advancement for patients with PD-L1–positive metastatic triple-negative breast cancer, a population for whom first-line options remain limited," said Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute and primary investigator of the ASCENT-04/KEYNOTE-D19 study. "By combining sacituzumab govitecan with pembrolizumab, we’re seeing meaningful gains in progression-free survival and a promising trend in overall survival—findings that could support a new frontline standard of care for this aggressive disease."

The safety profile of KEYTRUDA plus Trodelvy in this study was consistent with the known safety profile of each agent. No new safety signals were identified with the combination. The two companies plan to share these results with regulatory authorities worldwide.

"We’re committed to building on the established role of KEYTRUDA as a foundational treatment for people with TNBC to provide new options in earlier lines of treatment, in the hope of improving outcomes for people living with this disease," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "These data support the addition of this TROP2-directed ADC to KEYTRUDA, demonstrating the potential to help people with TNBC and to give doctors another option to treat this disease."

A statistically significant and clinically meaningful improvement was observed with KEYTRUDA plus Trodelvy (n=221), showing a 35% reduction in the risk of disease progression or death (HR=0.65; p<0.001) in the intent-to-treat population compared to KEYTRUDA plus chemotherapy (n=222). The PFS benefit was generally consistent across key prespecified subgroups including age, curative treatment-free interval and geographic region.

A higher objective response rate (ORR) was observed for the KEYTRUDA plus Trodelvy combination (59.7% [95% CI, 52.9-66.3] versus 53.2% [95% CI, 46.4-59.9]), including 13% and 8% with a complete response, respectively, in the KEYTRUDA plus Trodelvy and KEYTRUDA plus chemotherapy arms. Notably, a substantially longer duration of response (DOR) was observed with KEYTRUDA plus Trodelvy (16.5 months [95% CI, 12.7-19.5] versus 9.2 months [95% CI, 7.6-11.3]). Encouraging trends in overall survival (OS) were also observed, but data are immature at the time of PFS primary analysis. Overall survival follow-up remains ongoing and will continue to be monitored as a key secondary endpoint.

Merck has a comprehensive clinical development program in various subtypes of breast cancer including evaluating KEYTRUDA in combination with investigational TROP2 ADCs (trophoblast cell-surface antigen-directed antibody-drug conjugates) in metastatic and early-stage cancers. The company has four ongoing Phase 3 studies in breast cancer, with two being in metastatic disease.

In the U.S. and Europe, KEYTRUDA has two approved indications in TNBC: for the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery; and in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

As announced, data spanning more than 25 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting.

About the ASCENT-04/KEYNOTE-D19 Study

In 2021, Merck entered a collaboration with Gilead to investigate KEYTRUDA plus Trodelvy in the Phase 3 ASCENT-04/KEYNOTE-D19 open-label, global trial (ClinicalTrials.gov, NCT05382286). The primary endpoint is PFS as determined by BICR using RECIST v1.1. Secondary endpoints include OS, ORR, DOR, time to onset of response (TTR), patient-reported outcomes (PROs) and safety. The study enrolled 443 patients who were randomized in a 1:1 ratio to receive either sacituzumab govitecan (10 mg/kg intravenously [IV] on Days 1 and 8 of a 21-day cycle) plus pembrolizumab (200 mg IV on Day 1 of a 21-day cycle) or chemotherapy plus pembrolizumab. The chemotherapy regimen included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Treatment continued until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity and at this time patients randomized to chemotherapy were allowed to crossover and receive sacituzumab govitecan upon disease progression.

About triple-negative breast cancer (TNBC)

Triple-negative breast cancer is the most aggressive type of breast cancer, which has the highest risk of recurrence within the first five years after diagnosis and is associated with worse outcomes compared to other forms of breast cancer. Approximately 10-15% of patients with breast cancer are diagnosed with TNBC. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Triple-negative breast cancer tends to be more common in people who are younger than 40 years of age, who are Black or who have a BRCA1 mutation.

On May 31, 2025 Late-breaking (LBA4175) post-hoc analysis data from the Phase III NAPOLI 3 study were reported at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Ipsen, MAY 31, 2025, View Source [SID1234653546]). These results found a median overall survival (mOS) of 19.5 months among long-term survivors (n=15) with metastatic pancreatic adenocarcinoma (mPDAC) treated with the Onivyde (irinotecan liposome injection) plus oxaliplatin, fluorouracil and leucovorin (NALIRIFOX) regimen as a first-line treatment (n=120), with younger age at diagnosis, and certain tumor and metastasis locations associated with long-term survivorship.2

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Pancreatic adenocarcinoma (PDAC) is the most common type of cancer that forms in the pancreas, with more than 60,000 people diagnosed annually in the U.S. and nearly 500,000 people globally.3,4 It is often detected after the disease has spread to other parts of the body (metastatic or stage IV)5 and fewer than 20% of people diagnosed with metastatic pancreatic adenocarcinoma (mPDAC) survive longer than one year.5,6 Overall, pancreatic cancer has the lowest five-year survival rate of all cancer types globally and in the U.S.5,6

"When people are diagnosed with metastatic pancreatic adenocarcinoma, the most important question remains: how long will they have with their loved ones," said Dr. Vincent Chung, Medical Oncologist, City of Hope. "Findings from the NAPOLI 3 post-hoc analysis provide important context on long-term overall survival with the Onivyde (NALIRIFOX) treatment regimen."

The analysis included patients who survived for 18 months or longer (N=15), with findings showing long-term survivors living with mPDAC had a mOS of 19.5 months (interquartile range [IQR]: 18.8–22.6).2 Clinical and pathological factors of long-term survivors included younger than average age at time of diagnosis (median age 61.0 (IQR: 49.0–70.5) as well as tumor location.2 Fewer patients had tumors in the head or tail of the pancreas (53.3% had the main pancreatic tumor located in the body of the pancreas), a substantial proportion had liver metastasis (66.7%) and ≥3 metastatic sites (53.3%).2 Additionally, findings indicate dose reduction and treatment delays resulted in prolonged exposure and higher cumulative doses of the Onivyde (NALIRIFOX) regimen.1 Liver metastasis and ≥3 metastatic sites, dose modifications and an otherwise good clinical profile enabled people to achieve a long mOS.2 Consideration should be taken when interpreting these results as a post-hoc analysis with a small sample size.

"Data from the Phase III NAPOLI 3 trial were the first positive data of its kind in a decade and continue to reinforce the potential for long-term outcomes with the Onviyde (NALIRIFOX) regimen," said Sandra Silvestri, MD, PhD, Executive Vice President, Chief Medical Officer, Ipsen. "With people on average living just 4-6 months following diagnosis with pancreatic adenocarcinoma, these data help us to understand the characteristics associated with long-term survival seen in the NAPOLI trial, an important advancement for this difficult-to-treat cancer where data of this kind are scarce."

On May 31, 2025 Immatics N.V. (NASDAQ: IMTX, "Immatics" or the "Company"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported the presentation of expanded data from the ongoing Phase 1b clinical trial evaluating IMA203 PRAME cell therapy in heavily pretreated patients with metastatic melanoma (Press release, Immatics, MAY 31, 2025, View Source [SID1234653545]). The longer follow-up of patients demonstrates a consistent and favorable tolerability profile as well as durable responses with a confirmed ORR of 56%. In addition, the Company provided details from a Trial in Progress poster on SUPRAME, the ongoing Phase 3 clinical trial evaluating IMA203 in patients with unresectable or metastatic cutaneous melanoma who have received prior treatment with a checkpoint inhibitor.

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The data from the ongoing Phase 1b trial will be presented on Saturday, May 31, 2025, during an oral presentation by Martin Wermke, M.D. The Trial in Progress poster (TiP) will be presented at the conference on Monday, June 2, 2025, by Jason Luke, M.D., FACP, FASCO. The IMA203 slides, including the ASCO (Free ASCO Whitepaper) data and additional data, are accessible in the ‘Events & Presentations’ section of the Investor & Media section of the Company’s website.

"Patients with advanced melanoma post-failure of checkpoint inhibition are left to face frequent and often rapid disease progression and limited long-term survival. These individuals are in urgent need of new treatments that deliver deeper and more durable responses," said Cedrik Britten, M.D., Chief Medical Officer at Immatics. "We believe the data presented today emphasize the strength, durability and tangible therapeutic potential of our one-time infusion PRAME cell therapy, IMA203, in this patient population. These positive results reinforce our commitment to actively advance IMA203 through the ongoing Phase 3 SUPRAME trial to bring this PRAME therapy to the market as soon as possible."

"PRAME is a highly prevalent target that is expressed in more than 50 cancers. This, combined with the data presented at ASCO (Free ASCO Whitepaper), further strengthens our position as the global leader in precision targeting of PRAME. We view our progress in melanoma as a critical step in our journey to building the broadest PRAME franchise with the most indications and modalities and delivering novel PRAME immunotherapies to cancer patients with high unmet medical needs," said Harpreet Singh, Ph.D., Chief Executive Officer and Co-Founder at Immatics.

Oral Presentation Summary – IMA203 Phase 1b Trial

Patient Population: Heavily pretreated patients with metastatic melanoma

As of April 7, 2025, 33 heavily pretreated patients with metastatic melanoma were administered a one-time infusion of IMA203 at the recommended Phase 2 dose (RP2D, 1 to 10 billion total TCR T cells) in the Phase 1b dose expansion. The treated patient population consisted of cutaneous melanoma (n=14), uveal melanoma (n=16), mucosal melanoma (n=2) and melanoma of unknown primary (n=1). Patients had a median of 2 lines of prior systemic treatments. The subgroup of patients with cutaneous melanoma had a median of 2.5 lines of prior systemic treatments, thereof a median of 2 lines of prior immune checkpoint inhibitors.

Safety: Favorable tolerability

The safety population included 74 patients combined from the Phase 1a dose escalation and Phase 1b dose expansion across all dose levels and all tumor types. IMA203 has maintained a favorable tolerability profile.

The most frequent treatment-emergent adverse events were anticipated cytopenias associated with lymphodepletion. Expected and manageable cytokine release syndrome (CRS) was mostly Grades 1 and 2, which is consistent with the mechanism of action (Grade 1: 37%, Grade 2: 47%, Grade 3: 11%, Grade 4: 0%). No patients experienced long-term CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred infrequently, was manageable and mostly mild (Grade 1: 5%, Grade 2: 4%, Grade 3: 4%, Grade 4: 0%). No IMA203-related Grade 5 events were observed.

Tolerability in the Phase 1b melanoma subset was generally consistent with the full IMA203 tolerability profile.

Anti-tumor activity and durability: Encouraging anti-tumor activity of IMA203 PRAME cell therapy, including durable responses up to >2.5 years with longer follow-up

All melanoma1,2
(n=33) Cutaneous melanoma
(n=14) Uveal melanoma2
(n=16)

cORR 56% (18/32) 50% (7/14) 67% (10/15)
ORR 64% (21/33) 57% (8/14) 69% (11/16)
DCR 91% (30/33) 93% (13/14) 88% (14/16)
mDOR (range) / mFU [mo] 12.1 (1.8+, 32.6+) / 13.4 NR3 (4.2, 32.6+) / 16.7 11.0 (1.8+, 31.6) / 13.4
mPFS (range) / mFU [mo] 6.1 (1.4, 34.0+) / 14.4 6.0 (1.4, 34.0+) / 14.4 8.5 (1.4, 32.9) / 8.7
mOS (range) / mFU [mo]

15.9 (2.4, 34.2+) / 14.4 13.9 (2.4, 34.0+) / 14.4 16.2 (3.2+, 34.2+) / 14.5
The PFS rate was 53% at six months and 27% at 12 months. The overall survival rate was 61% at 12 months. In addition, 42% (14/33) of patients had a deep response (≥50% tumor reduction) with a mPFS of 12.9 months.

Translational analyses demonstrated that treatment with IMA203 resulted in the shrinkage of metastatic target lesions throughout the body. This included reductions in difficult-to-treat metastases, such as liver, lung, lymph node, abdomen/peritoneum, skin and others. Some individual lesions had a complete resolution (-100%). All patients (n=3) who had a best overall response of progressive disease according to RECIST 1.1 experienced shrinkage of individual lesions.

The positive Phase 1b data and high PRAME prevalence (~90-95% in melanoma) reinforce the potential of IMA203, which is currently being evaluated in the ongoing SUPRAME Phase 3 trial in previously treated advanced or metastatic cutaneous melanoma, as well as the continued Phase 1b expansion into uveal melanoma.

Trial-in-Progress Poster Summary – IMA203 SUPRAME Phase 3 Trial

Based on the positive clinical data and supported by the FDA RMAT designation4, Immatics advanced its PRAME cell therapy, IMA203, into the randomized-controlled Phase 3 SUPRAME trial (NCT06743126).

SUPRAME is a prospective, multicenter, open-label, randomized, actively controlled Phase 3 clinical trial evaluating the efficacy, safety and tolerability of IMA203 vs. investigator’s choice in ~360 patients with unresectable or metastatic cutaneous melanoma who have received prior treatment with a checkpoint inhibitor. Patient eligibility is determined by protocol inclusion/exclusion criteria, including HLA screening. If patients are HLA-A*02:01 positive and meet the eligibility criteria, they will undergo leukapheresis and be randomized 1:1. Patients in the IMA203 arm will undergo lymphodepletion with cyclophosphamide (500 mg/m2 x 4 days) and fludarabine (30 mg/m2 x 4 days), subsequent infusion of 1-10 x109 IMA203 PRAME-directed TCR T cells, followed by low-dose IL-25 (subcutaneous). Patients in the control arm will receive either nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (in the US), or chemotherapy based on investigator’s choice. The primary endpoint is blinded independent central review ("BICR")-assessed (RECIST 1.1) PFS. Secondary endpoints include OS, ORR, safety and patient-reported outcomes about quality of life.

The expected median PFS in this post-checkpoint inhibitor patient population6 is 2-3 months, and the IMA203 Phase 1b data presented today at ASCO (Free ASCO Whitepaper) indicate a continued median PFS of ≥6 months.

SUPRAME is planned to be conducted in more than 50 sites in North America and Europe.

Patient enrollment and randomization for the trial was initiated in early 2025 and is expected to be completed in 2026. A pre-specified interim data analysis will be triggered upon the occurrence of a defined number of events for PFS (progressive disease or death)7, anticipated to occur after approximately 200 patients. Immatics aims to submit a Biologics License Application (BLA) to the FDA in 1Q 2027 for full approval.

About PRAME
PRAME is a target expressed in more than 50 cancers. Immatics is the global leader in precision targeting of PRAME and has the broadest PRAME franchise with the most PRAME indications and modalities. The Immatics PRAME franchise currently includes three product candidates, two therapeutic modalities and a combination therapy that target PRAME: IMA203 PRAME cell therapy, IMA203CD8 PRAME cell therapy (GEN2), IMA402 PRAME bispecific, IMA203 in combination with Moderna’s PRAME adaptive immune modulating therapy.

About IMA203 PRAME Cell Therapy
IMA203 is a PRAME-directed TCR T-cell therapy engineered to recognize an intracellular PRAME-derived peptide presented by HLA-A*02:01 on the cell surface and initiate a potent and specific anti-tumor response. IMA203 PRAME cell therapy is currently being evaluated in a registration-enabling randomized controlled Phase 3 trial, "SUPRAME," in patients with unresectable or metastatic cutaneous melanoma who have disease progression on or after treatment with at least one checkpoint inhibitor. In parallel, the Phase 1b clinical trial in patients with PRAME cancers is ongoing with a focus on uveal melanoma.

On May 31, 2025 Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) reported detailed results from the Phase 3 VERITAC-2 clinical trial (NCT05654623) evaluating vepdegestrant monotherapy versus fulvestrant in adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer (MBC) whose disease progressed following prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapy (Press release, Arvinas, MAY 31, 2025, View Source [SID1234653542]). These data, which were highlighted in the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) press briefing and selected for Best of ASCO (Free ASCO Whitepaper), will be presented today in a late-breaking oral presentation (Abstract LBA1000) and have been simultaneously published in the New England Journal of Medicine.

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In the trial, vepdegestrant demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) among patients with an estrogen receptor 1 (ESR1) mutation, reducing the risk of disease progression or death by 43% compared to fulvestrant [Hazard Ratio (HR)=0.57 (95% CI 0.42–0.77); 2-sided P<0.001]. The median PFS, as assessed by blinded independent central review (BICR), was 5.0 months with vepdegestrant versus 2.1 months with fulvestrant. Investigator-assessed PFS was consistent with the BICR-assessed PFS. In patients with ESR1 mutations, vepdegestrant demonstrated a consistent PFS benefit over fulvestrant across all pre-specified subgroups. The trial did not reach statistical significance in improvement in PFS in the intent-to-treat (ITT) population, with a median PFS of 3.7 months for vepdegestrant versus 3.6 for fulvestrant [HR=0.83 (95% CI 0.68–1.02); 2-sided P=0.07].

"Many patients with ER+/HER2- metastatic breast cancer who progress on endocrine therapy have tumors with ESR1 mutations, which drive resistance to standard treatments," said Erika P. Hamilton, M.D., Director, Breast Cancer Research, Sarah Cannon Research Institute, and a principal investigator of the VERITAC-2 trial. "The VERITAC-2 results are promising and suggest that vepdegestrant could offer a much-needed treatment option for these patients, with a low incidence of burdensome GI effects that can meaningfully affect daily life."

Vepdegestrant was generally well tolerated in the trial, with a safety profile consistent with what has been observed in previous studies, and mostly low-grade treatment-emergent adverse events (TEAEs). Rates and severity of gastrointestinal adverse events were low with vepdegestrant (nausea, 13.5%; vomiting, 6.4%; diarrhea, 6.4%). Grade 4 TEAEs were reported in 5 patients (1.6%) in the vepdegestrant arm versus 9 patients (2.9%) in the fulvestrant arm. The three most common TEAEs observed with vepdegestrant were fatigue (26.6%), increased alanine transaminase (ALT) (14.4%) and increased aspartate aminotransferase (AST) (14.4%). TEAEs leading to treatment discontinuation occurred in 2.9% of patients taking vepdegestrant versus 0.7% of patients taking fulvestrant.

"Based on these strong data from VERITAC-2, we believe that vepdegestrant has the potential to be a best-in-class monotherapy treatment for patients in the second-line ESR1-mutant setting," said John Houston, Ph.D., Chairperson, Chief Executive Officer and President at Arvinas. "We are excited to engage with regulatory authorities on next steps to potentially bring vepdegestrant to healthcare providers and their patients as swiftly as possible."

Overall survival (OS), the key secondary endpoint in VERITAC-2, was immature at the time of the analysis, with less than a quarter of the required number of events having occurred. Additional secondary endpoints include clinical benefit rate (CBR) and objective response rate (ORR) and duration of response by BICR. In patients with an ESR1 mutation, CBR was 42.1% with vepdegestrant versus 20.2% with fulvestrant [odds ratio 2.88 (95% CI: 1.57–5.39); nominal P<0.001] and ORR was 18.6% with vepdegestrant versus 4.0% with fulvestrant [odds ratio 5.45 (95% CI: 1.69–22.73); nominal P=0.001]. The median duration of response was not reached.

"Patients whose tumors harbor ESR1 mutations can face a poor prognosis, often experiencing rapid disease progression on endocrine therapy," said Johanna Bendell, M.D., Chief Oncology Development Officer, Pfizer. "These results highlight the important role vepdegestrant may play in combating ESR1 mutation treatment resistance for these patients."

Approximately 2.3 million new breast cancer diagnoses were reported globally in 2022, and it is estimated there will be nearly 320,000 new diagnoses in the United States in 2025. ER+/HER2- breast cancer accounts for approximately 70% of all cases. Nearly 30% of women initially diagnosed with early-stage breast cancer will ultimately develop metastatic disease,1 with resistance to current standard-of-care treatments often emerging during first-line therapy, leading to disease progression. ESR1 mutations are a common cause of acquired resistance and are found in approximately 40% of patients in the second-line setting.2,3,4

Vepdegestrant, an investigational oral PROTAC ER degrader for ER+/HER2- breast cancer being jointly developed by Arvinas and Pfizer, is designed to harness the body’s natural protein disposal system to specifically target and degrade the ER. These detailed results follow the March 2025 announcement of the topline results from VERITAC-2. The companies plan to submit a New Drug Application (NDA) for vepdegestrant to the U.S. Food & Drug Administration (FDA) in the second half of 2025.

ASCO Presentation Details
"Vepdegestrant, a PROTAC Estrogen Receptor Degrader, vs Fulvestrant in ER-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results of the Global, Randomized, Phase 3 VERITAC-2 Study" will be presented by Dr. Erika Hamilton, MD, Sarah Cannon Research Institute, in the Oral Abstract Session, Breast Cancer—Metastatic on Saturday, May 31, 1:15 – 4:15 p.m. CDT in Hall B1. Abstract LBA1000.

Investor Call and Webcast Details
Arvinas will host a conference call and webcast on June 2, 2025, at 8:00 a.m. ET to review these data. Participants are invited to listen by going to the Events and Presentation section under the Investors page on the Arvinas website at www.arvinas.com. A replay of the webcast will be available on the Arvinas website following the completion of the event and will be archived for up to 30 days.

About the VERITAC-2 Clinical Trial
The Phase 3 VERITAC-2 clinical trial (NCT05654623) is a global randomized trial evaluating the efficacy and safety of vepdegestrant (ARV-471) as a monotherapy compared to fulvestrant in patients with ER+/HER2- advanced or metastatic breast cancer. The trial enrolled 624 patients at sites in 26 countries who had previously received treatment with a CDK4/6 inhibitor plus endocrine therapy.

Patients were randomized 1:1 to receive either vepdegestrant once daily, orally on a 28-day continuous dosing schedule, or fulvestrant, administered intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each 28-day cycle starting from Day 1 of Cycle 2. In the trial, 43% of patients (n=270) had ESR1 mutations detected. The primary endpoint was progression-free survival (PFS) in the ESR1-mutation and intent-to-treat populations as determined by blinded independent central review. Overall survival is the key secondary endpoint.

About Vepdegestrant
Vepdegestrant is an investigational, orally bioavailable PROteolysis TArgeting Chimera (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 for ER+/HER2- advanced or metastatic breast cancer with estrogen receptor 1 (ESR1) mutations in the second line-plus setting.

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.

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- advanced or metastatic breast cancer previously treated with endocrine-based therapy.