On December 11, 2025 Avenzo Therapeutics, Inc. ("Avenzo"), a clinical-stage biotechnology company developing next-generation oncology therapies, reported initial clinical data from the Phase 1 portion of its ongoing Phase 1/2 clinical study of AVZO-021, its potential best-in-class cyclin-dependent kinase 2 (CDK2) selective inhibitor. The initial data highlighted preliminary clinical activity, including objective responses across patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer and cyclin E1 (CCNE1)-amplified ovarian cancer. AVZO-021 was generally well tolerated with relatively low incidence and severity of gastrointestinal and hematologic adverse events, which are commonly observed adverse events associated with other CDK inhibitors.

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The findings were reported at the 2025 San Antonio Breast Cancer Symposium.

"CDK2 has emerged as an important resistance mechanism in patients with HR+/HER2- breast cancer, especially for patients who progress on CDK4/6 inhibitors," said Alberto J. Montero, M.D., MBA, Clinical Director, Breast Cancer Medical Oncology Program and Diana Hyland Endowed Chair for Breast Cancer at University Hospitals Seidman Cancer Center, Case Western Reserve University. "These data reported today for AVZO-021 are exciting as they not only demonstrate the activity and tolerability of AVZO-021, but the potential for its use in combination with other agents."

AVZO-021, Phase 1 Initial Clinical Data

Utilizing an October 10, 2025 data cut-off date, 35 patients with advanced solid tumors were treated with AVZO-021 monotherapy across nine dose levels, and 10 patients with HR+/HER2- breast cancer were treated with AVZO-021 in combination with fulvestrant across two AVZO-021 dose levels.

The median number of prior therapies in the metastatic setting was 3.0 (range zero to 11), with all patients with HR+/HER2- breast cancer having received at least one prior CDK4/6 inhibitor.

Efficacy-evaluable patients included 19 patients with HR+/HER2- breast cancer or CCNE1-amplified solid tumors treated with AVZO-021 monotherapy doses of 150 mg once daily (QD) and above with at least one post-baseline scan, and nine patients with HR+/HER2- breast cancer treated with AVZO-021 in combination with fulvestrant with at least one post-baseline scan.

As of the October 10, 2025 data cut-off date:

Initial Safety Results

A total of 45 patients comprise the safety population, including 35 patients with advanced solid tumors treated with AVZO-021 monotherapy at dose levels from 20 mg QD to 250 mg QD, and 10 patients with HR+/HER2- breast cancer treated with AVZO-021 in combination with fulvestrant at AVZO-021 dose levels of 150 mg QD and 200 mg QD.
All-grade treatment emergent adverse events (TEAEs) reported in greater than 20 percent of patients were nausea (44%), fatigue (38%), anemia (33%), and vomiting (29%).
The majority of TEAEs were Grade 1 or Grade 2, and no patients had TEAEs leading to treatment discontinuation.
Initial Pharmacokinetic and Pharmacodynamic Results

PK data suggested continuous CDK2 target coverage was achieved at doses of 90 mg QD and above.
Comparable exposures of AVZO-021 were observed between AVZO-021 monotherapy and in combination with fulvestrant at 150 mg QD, indicating no drug-drug interaction.
Significant decreases in circulating tumor DNA (ctDNA) were observed.
Initial Efficacy Results

Of 19 efficacy-evaluable patients treated with AVZO-021 monotherapy, three patients experienced confirmed responses, including two with HR+/HER2- breast cancer with onset at weeks 15 and 36 and one with CCNE1-amplified ovarian cancer with onset at week 35. Seven patients, who remain on treatment, achieved stable disease, including six with HR+/HER2- breast cancer.
Of nine efficacy evaluable HR+/HER2- breast cancer patients treated with AVZO-021 in combination with fulvestrant, one patient experienced a confirmed response, with onset at week 7; the confirmatory scan was obtained after the data cut-off date. Three patients, who remain on treatment, achieved stable disease.
All responders remain on treatment with two on treatment for greater than 48 weeks.
"We are encouraged by the initial safety and efficacy data from this study, especially given multiple patients show improvement over time and remain on treatment," said Mohammad Hirmand, M.D., Co-founder and Chief Medical Officer of Avenzo Therapeutics. "We look forward to advancing the development of AVZO-021 in combination with our highly potent and selective CDK4 inhibitor, AVZO-023."

In addition, the company presented the study design for the ongoing Phase 1/2 study evaluating AVZO-023, its potential best-in-class cyclin-dependent kinase 4 (CDK4) selective inhibitor, as a single agent and in combination with AVZO-021 and/or endocrine therapy at the 2025 San Antonio Breast Cancer Symposium.

(Press release, Avenzo Therapeutics, DEC 11, 2025, View Source [SID1234661368])

On December 10, 2025 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive data from the phase III lidERA Breast Cancer study evaluating investigational giredestrant as an adjuvant endocrine treatment for people with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2-negative, early-stage breast cancer.1 At the pre-specified interim analysis, adjuvant giredestrant significantly reduced the risk of invasive disease recurrence or death by 30% (invasive disease-free survival [iDFS]) compared with standard-of-care endocrine therapy (SoC ET) (hazard ratio [HR]=0.70, 95% confidence interval [CI] 0.57-0.87, p=0.0014).1 The lidERA results are being presented at the 2025 San Antonio Breast Cancer Symposium and are included in the official press programme.

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"In early ER-positive breast cancer, challenges with disease recurrence and treatment adherence mean there is an urgent need for more effective, tolerable endocrine therapies," said Aditya Bardia, M.D., M.P.H, Director, Breast Oncology Program, Professor of Medicine at the David Geffen School of Medicine at University of California, Los Angeles (UCLA), Director of Translational Research Integration at the UCLA Health Jonsson Comprehensive Cancer Center, and lidERA principal investigator. "After almost 25 years, a new medicine – giredestrant – has demonstrated superiority over existing endocrine therapies in the curative setting, highlighting its potential as a new standard-of-care endocrine therapy for patients with breast cancer."

"The substantial efficacy observed with giredestrant in the lidERA trial underscores its potential to become a new standard-of-care endocrine therapy in ER-positive early-stage breast cancer, where the chance for cure is highest," said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. "We look forward to sharing these results with health authorities around the world with the aim of bringing this new treatment option to patients as soon as possible."

At three years, 92.4% of patients in the giredestrant arm were alive and free of invasive disease versus 89.6% in the SoC ET arm.1 The iDFS benefit was consistent across all clinically relevant subgroups.1 Overall survival (OS) data were immature at the time of this analysis, but a clear positive trend was observed.1 Follow-up for OS will continue to the next analysis. Giredestrant also demonstrated a 31% risk reduction of distant recurrence-free interval (HR=0.69, 95% CI 0.54-0.89) – another key secondary endpoint.1 Giredestrant was well tolerated; adverse events were manageable and consistent with its known safety profile.1

ER-positive breast cancer accounts for approximately 70% of breast cancer cases, and the majority are diagnosed in the early-stage.4,5 Currently, up to a third of people eventually experience recurrence on or after adjuvant endocrine therapy treatment for early-stage breast cancer.5-7 Additionally, many have to interrupt or stop treatment early due to safety or tolerability issues, thereby increasing the risk of death.8,9 These limitations underscore the need for more effective and better-tolerated options that can enhance adherence and prevent or delay disease recurrence.

Giredestrant is the first and only oral selective oestrogen receptor degrader (SERD) to show superior iDFS in the adjuvant setting and lidERA is the second positive phase III readout for giredestrant following the evERA Breast Cancer results in the metastatic setting.1,10 The scientific rationale for lidERA was supported by prior results in the neoadjuvant setting, including the coopERA trial showing that giredestrant was superior to an aromatase inhibitor in reducing malignant cell division (Ki67 levels).11 This growing body of evidence supports the potential of giredestrant to meaningfully improve outcomes compared with standard-of-care endocrine therapy across ER-positive early-stage and advanced breast cancer.1,10,11

Roche’s extensive giredestrant clinical development programme spans multiple treatment settings and lines of therapy, reflecting our commitment to deliver innovative medicines to as many people with ER-positive breast cancer as possible.

About the lidERA Breast Cancer study
lidERA Breast Cancer [NCT04961996] is a phase III, randomised, open-label, multicentre study evaluating the efficacy and safety of adjuvant giredestrant versus standard-of-care endocrine therapy in people with medium- or high-risk stage I-III oestrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer.12 Over 4,100 patients were enrolled in the study.12

The primary endpoint is invasive disease-free survival (iDFS) excluding unrelated cancers in other organs (second primary non-breast cancers).12 Key secondary endpoints include overall survival, iDFS including second primary non-breast cancers, disease-free survival and safety.12

About giredestrant
Giredestrant is an investigational, oral, potent next-generation selective oestrogen receptor degrader and full antagonist.13

Giredestrant is designed to block oestrogen from binding to the oestrogen receptor, triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells.14

Giredestrant has an extensive clinical development programme and is being investigated in five company-sponsored phase III clinical trials that span multiple treatment settings and lines of therapy to benefit as many people as possible:

Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)12
Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)15
Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009)16
Giredestrant plus investigator’s choice of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor versus fulvestrant plus a CDK4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748)17
Giredestrant plus Phesgo (pertuzumab, trastuzumab, and hyaluronidase subcutaneous) versus Phesgo in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798)18
About oestrogen receptor (ER)-positive breast cancer
Globally, the burden of breast cancer continues to grow, with 2.3 million women diagnosed and 670,000 dying from the disease every year.19 Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.20

ER-positive breast cancer accounts for approximately 70% of breast cancer cases.4 A defining feature of ER-positive breast cancer is that its tumour cells have receptors that attach to oestrogen, which can contribute to tumour growth.

Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity.22 Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy.5-9,22,23 There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.

(Press release, Hoffmann-La Roche, DEC 10, 2025, View Source [SID1234661370])

On December 10, 2025 InduPro, Inc., a biotechnology company defining membrane protein spatial relationships to create novel therapeutics for the treatment of cancer and autoimmune diseases, reported a strategic equity investment and research collaboration with Sanofi. The agreement with Sanofi includes the right of first negotiation for InduPro’s bispecific PD-1 agonist program, which is currently in preclinical development for the treatment of autoimmune and inflammatory disorders.

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"We are thrilled to collaborate with Sanofi to advance toward the clinic our bispecific PD-1 agonist program. Sanofi’s know-how and global leadership position in autoimmune and inflammatory diseases make them the ideal partner to bring this exciting first-in-class molecule forward," said Prakash Raman, Ph.D., Chief Executive Officer of InduPro. "In addition, we welcome Sanofi’s strategic equity investment into InduPro, which further reinforces the strength of our collaboration."

Under the terms of the agreement, InduPro and Sanofi will collaborate on preclinical and IND-enabling research activities with funding from Sanofi, which will also make an undisclosed equity investment in InduPro.

InduPro therapeutically targets cell surface proteins in a variety of disease contexts by leveraging inherent or induced protein proximity. Through precise mapping of protein neighborhoods using its proprietary, high resolution proximity labeling technology, the Company is discovering novel co-target pairs that are highly selective for specific disease biology. Targeting these unique pairings via induced proximity provides a novel mechanism for influencing the cellular signaling pathways that are critical for impacting disease. InduPro’s approach relies on a unique discovery engine to generate potential first-in-class and best-in-class novel therapeutic candidates across multiple indications and modalities.

(Press release, InduPro, DEC 10, 2025, View Source [SID1234661365])

On December 10, 2025 NeoGenomics, Inc. (NASDAQ: NEO), a leading provider of oncology diagnostic solutions that enable precision medicine, reported that data utilizing its RaDaR 1.0 assay for the detection of molecular residual disease (MRD) will be presented at the 2025 San Antonio Breast Cancer Symposium (SABCS), taking place Dec. 9–12, 2025, at the Henry B. Gonzalez Convention Center in San Antonio, Texas.

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NeoGenomics will present new data from the SURVIVE HERoes Phase III trial and the CLEVER study, both of which used RaDaR 1.0 circulating tumor DNA (ctDNA) testing to evaluate molecular residual disease and recurrence risk. These findings reinforce the growing role of tumor-informed ctDNA approaches in early breast cancer research and recurrence monitoring.

Presentation details

The first study, titled "5-year outcomes and ctDNA findings in the CLEVER trial targeting disseminated dormant tumor cells," investigates long-term recurrence biology in patients with high-risk breast cancer and shows that positive ctDNA frequently precedes clinical recurrence. Five-year follow-up data demonstrate that RaDaR-detected ctDNA was present in most patients with disseminated tumor cells, often months before relapse. These findings reinforce the potential role that sensitive ctDNA testing can play in monitoring molecular residual disease during periods of ongoing long-term risk. Investigators from the University of Pennsylvania will present on Thursday, Dec. 11, 2025, 7:00 AM–8:30 AM CST. [PD5-02]

The SURVIVE Phase III randomized case-control trial, presented as "Reevaluating Follow-Up in Early Breast Cancer, guided by Liquid Biopsy: the SURVIVE Study (NCT05658172)," investigates whether the use of the RaDaR assay in liquid-biopsy guided follow-up may enable earlier detection of recurrence and improve overall survival. Investigators from the University Hospital Ulm, Germany, presenting on behalf of recruiting centers across Germany, will share the current status on Friday, Dec. 12, 2025, 12:30 PM–2:00 PM CST. [PS5-08-13]

The SURVIVE HERoes Phase III trial, presented as "The SURVIVE HERoes study NCT06643585: Targeting molecular relapse in breast cancer," is an ongoing therapeutic intervention arm of the SURVIVE trial, which evaluates an emerging strategy for treating patients at the point of molecular relapse, when ctDNA is detectable when using the RaDaR assay despite no radiographic evidence of disease. The study examines whether earlier intervention in HER2-positive or HER2-low early breast cancer can improve long-term outcomes. Positive study results could help establish a new, molecularly guided, individualized surveillance and treatment approach. Investigators from the University Hospital Ulm will present on Friday, Dec.12, 2025, 12:30 PM–2:00 PM CST. [PS5-07-28]

"The findings presented at this year’s SABCS conference demonstrate how RaDaR-detected ctDNA can provide invaluable and actionable information to care teams as they monitor patients following their initial breast care treatment," said Tony Zook, Chief Executive Officer. "These studies represent an important step in building the evidence needed to integrate MRD insights into the routine oncology care that community oncologists and their patients deserve."

(Press release, NeoGenomics Laboratories, DEC 10, 2025, View Source [SID1234661364])

On December 10, 2025 Pfizer Inc. (NYSE: PFE) reported detailed results from the Phase 3 HER2CLIMB-05 trial of the tyrosine kinase inhibitor TUKYSA (tucatinib) as part of an investigational first-line maintenance treatment combination, following chemotherapy-based induction, in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). The primary endpoint analysis showed a 35.9% reduction in the risk of disease progression or death among patients treated with TUKYSA, trastuzumab, and pertuzumab compared to those treated with placebo, trastuzumab, and pertuzumab, as assessed by the investigator (hazard ratio [HR] of 0.641, 95% confidence interval (CI): 0.514-0.799; 2-sided p<0.0001). These findings were published today in the Journal of Clinical Oncology, shared in an oral presentation at the 48th San Antonio Breast Cancer Symposium (SABCS), and highlighted in the SABCS official press program.

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In HER2CLIMB-05, the median progression-free survival (PFS) was 24.9 months (95% CI: 21.3-not reached) in the TUKYSA arm and 16.3 months (95% CI:12.6-18.7) in the placebo arm, representing an extension in median PFS of 8.6 months. A PFS benefit was observed across all prespecified patient subgroups, including de novo or recurrent diagnosis, hormone receptor (HR)-positive or HR-negative disease, and with or without the presence or history of brain metastases at baseline. The key secondary endpoint of overall survival was not mature at the time of the analysis (20% of the required events have occurred to date) but showed a numerical trend for improvement with TUKYSA.

"Most patients with HER2-positive metastatic breast cancer face disease progression within two years of starting first-line treatment, often requiring a transition to chemotherapy," said Erika Hamilton, M.D., principal investigator of HER2CLIMB-05 and Director of Breast Cancer Research for Sarah Cannon Research Institute (SCRI). "These results demonstrate that adding tucatinib to first-line maintenance therapy extends the time patients live without their disease progressing, while maintaining a manageable safety profile, suggesting a promising new potential approach that could advance the current standard of care for HER2-positive disease."

TUKYSA in combination with trastuzumab and pertuzumab demonstrated a safety profile generally consistent with the established safety profiles of each individual therapy, except for a higher rate of asymptomatic Grade ≥3 liver transaminases, which were typically manageable and reversible with TUKYSA dose modifications and/or discontinuations. The most common adverse events observed in the TUKYSA combination arm were diarrhea, hepatic events, and nausea.

"TUKYSA has become a trusted standard of care for patients with later-line HER2-positive metastatic breast cancer, and the results from HER2CLIMB-05 support its potential use as part of a chemotherapy-free, front-line maintenance strategy," said Jeff Legos, Chief Oncology Officer, Pfizer. "At Pfizer, we are committed to advancing treatment options that meaningfully improve the lives of people with metastatic breast cancer, and we are proud to share these promising results for patients and their families."

TUKYSA is not currently approved for first-line treatment. The results from HER2CLIMB-05 will be discussed with regulatory authorities. Since its initial approval in 2020, TUKYSA in combination with trastuzumab and capecitabine has become a standard of care for HER2+ MBC patients in the third-line setting. TUKYSA is currently approved in more than 50 countries; in the United States, TUKYSA is approved for use in combination with trastuzumab and capecitabine for adult patients with advanced unresectable or metastatic HER2+ breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

About HER2-Positive Metastatic Breast Cancer (MBC)
HER2 is overexpressed in up to 15-20% of breast cancers and is associated with poor prognosis, with an estimated five-year survival rate for HER2+ MBC of 41-47%, depending on HR status.1-3 First-line standard-of-care maintenance treatment has remained unchanged since 2012, and the majority of patients with HER2+ MBC face disease progression within two years of initiating therapy.4 Until recently, there have been limited advancements for these patients.

About the HER2CLIMB-05 Trial
HER2CLIMB-05 is a randomized, double blind, placebo-controlled, pivotal Phase 3 study evaluating the efficacy and safety of TUKYSA (tucatinib) compared to placebo, both in combination with trastuzumab and pertuzumab, as maintenance therapy for patients with HER2+ MBC following induction therapy in the first-line setting.

Trial participants who completed induction therapy of trastuzumab, pertuzumab, and a taxane, with no evidence of progression were randomized to receive TUKYSA in combination with trastuzumab plus pertuzumab (n=326), or placebo in combination with trastuzumab plus pertuzumab (n=328). The primary endpoint is progression-free survival (PFS) as assessed by the investigator. Key secondary endpoints include overall survival.

About TUKYSA (tucatinib)
TUKYSA (tucatinib) is an orally administered tyrosine kinase inhibitor of HER2. TUKYSA is approved in combination with trastuzumab and capecitabine to treat adults with HER2-positive advanced unresectable or metastatic breast cancer, including patients with brain metastases who have received one or more prior anti-HER2 breast cancer treatments in the metastatic setting.

The full U.S. Prescribing Information for TUKYSA can be found here.

IMPORTANT TUKYSA (tucatinib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Warning and Precautions:

Diarrhea: TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 0.5% with Grade 4 diarrhea and 12% with Grade 3 diarrhea. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB.
Hepatotoxicity: TUKYSA can cause severe hepatotoxicity. Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatotoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase > 5 × ULN, 6% had an AST increase > 5 × ULN, and 1.5% had a bilirubin increase > 3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of TUKYSA in 8% of patients and discontinuation of TUKYSA in 1.5% of patients.
Embryo-fetal Toxicity: TUKYSA can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TUKYSA and for 1 week after the last dose.
Adverse Reactions:
In HER2CLIMB, serious adverse reactions occurred in 26% of patients who received TUKYSA. Serious adverse reactions in ≥ 2% of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock. Adverse reactions leading to treatment discontinuation occurred in 6% of patients who received TUKYSA. Adverse reactions leading to treatment discontinuation of TUKYSA in ≥1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions leading to dose reduction occurred in 21% of patients who received TUKYSA. Adverse reactions leading to dose reduction of TUKYSA in ≥2% of patients were hepatotoxicity (8%) and diarrhea (6%). The most common adverse reactions in patients who received TUKYSA (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia, and rash.

Laboratory Abnormalities:
In HER2CLIMB, Grade ≥3 laboratory abnormalities reported in ≥5% of patients who received TUKYSA were decreased phosphate, increased ALT, decreased potassium, and increased AST. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

(Press release, Pfizer, DEC 10, 2025, View Source [SID1234661363])