On September 16, 2024 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported updated data, including median progression-free survival (mPFS) and overall survival (OS) findings, from the Phase 2 trial of zanidatamab, an investigational dual HER2-targeted bispecific antibody, in combination with chemotherapy as first-line treatment for patients with HER2-expressing advanced or metastatic gastroesophageal adenocarcinoma (mGEA) (Press release, Jazz Pharmaceuticals, SEP 16, 2024, View Source [SID1234646675]).

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Data from 41 patients with HER2-positive mGEA who were treated with zanidatamab in combination with physician’s choice of chemotherapy treatment demonstrated a mPFS of 15.2 [95% CI: 9.5, 33.4] months. After a median duration of follow-up of 41.5 (range, 23.0-52.7) months, the median OS was not mature, a Kaplan-Meier–estimated 24-month OS was 65% [95% CI: 48.0, 78.0] and the 30-month overall survival was 59% [95% CI: 41.0, 73.0].

"Gastroesophageal adenocarcinoma (GEA) represents one of the most common tumor types worldwide; however, developing effective treatment options for GEA patients has been challenging," said Dr. Elena Elimova, lead trial investigator and a medical oncologist at Princess Margaret Cancer Centre, Toronto, Canada. "Despite recent advancements for patients, the sustained clinical antitumor activity seen in this trial demonstrates the potential for zanidatamab to address a significant unmet patient need in HER2-positive GEA."

"The updated results from this Phase 2 trial reaffirm zanidatamab’s potential as a foundational treatment for patients with HER2-positive mGEA and showcase the promise of this HER2-targeted bispecific antibody to treat HER2-expressing cancers," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "We look forward to continuing to advance our broader clinical development program for zanidatamab in GEA, including the Phase 3 first-line clinical trial HERIZON-GEA-01 that is expected to read out in the second quarter of 2025, and other HER2-expressing solid tumors, with the goal of supporting more patients with HER2-positive cancers."

Phase 2 mGEA Trial Results
The data include efficacy and tolerability findings from an ongoing, open-label Phase 2 study (NCT03929666) evaluating zanidatamab in combination with chemotherapy as first-line treatment for patients with HER2-expressing mGEA, which comprises gastric, esophageal and gastroesophageal junction (GEJ) adenocarcinomas. Patients had not received prior HER2-targeted agents nor systemic treatment for mGEA. A total of 46 patients with HER2-expressing mGEA (41 patients with HER2-positive mGEA) were enrolled from 15 sites across the United States, Canada and South Korea, and patients were administered zanidatamab with physician’s choice of chemotherapy treatment. Currently, chemotherapy-based regimens are the standard first-line combination therapy for 1L mGEA.

The longer-term data (median duration of follow-up of 41.5 [range, 23.0-52.7] months) demonstrates the promising antitumor activity of zanidamatab combined with chemotherapy as a first-line therapy for HER2-positive mGEA.

Treatment with zanidatamab resulted in a cORR of 84% [95% CI: 68.0, 94.0], an increase of 5% from the cORR previously reported, and one additional patient achieved a complete response for a total of four patients achieving complete response among 37-response evaluable patients.
The median duration of response was 18.7 months [95% CI: 8.3-NE] with 10 patients having an ongoing response at the time of data cutoff.
The mPFS was 15.2 [95% CI: 9.5, 33.4] months.
The Kaplan-Meier–estimated 24-month OS was 65% [95% CI: 48.0, 78.0] with a 30-month overall survival of 59% [95% CI: 41.0, 73.0].
With additional follow-up, the safety and tolerability profile of zanidatamab plus chemotherapy remained manageable with no new safety signals identified. Diarrhea was the most common Grade 3-4 treatment-related adverse events (TRAEs) (35%); the incidence of Grade 3-4 diarrhea was <15% for patients treated after the implementation of mandated antidiarrheal prophylaxis. Treatment discontinuation due to TRAEs were infrequent, and there were no treatment-related deaths.

These data were presented in a poster session entitled Zanidatamab + Chemotherapy for First-Line Treatment for HER2+ Advanced or Metastatic Gastroesophageal Adenocarcinoma (mGEA) during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting taking place in Barcelona, Spain. The presentation is available to conference registrants on the ESMO (Free ESMO Whitepaper) conference website (Presentation Number 1423P).

Jazz continues to enroll patients in the Phase 3 randomized clinical trial, HERIZON-GEA-01 (NCT05152147), evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab as a first-line treatment for HER2-expressing mGEA. This is an events-based trial; top-line data from this trial is expected to read out in the second quarter of 2025.

Phase 2 Colorectal Cancer (CRC) Trial Results Presented as Mini-Oral at ESMO (Free ESMO Whitepaper) 2024
In addition to the mGEA trial presentation, a mini-oral was also presented at ESMO (Free ESMO Whitepaper) 2024 from another arm of the same Phase 2, open-label trial (NCT03929666) that includes a cohort of patients with metastatic CRC treated with first-line zanidatamab plus chemotherapy ± bevacizumab (bev). In 11 response-evaluable patients, there were 10 confirmed partial responses and 1 patient with stable disease as a best response. The cORR was 91% (95% CI: 58.7, 99.8) and median duration of response was not reached (2.9+,16.7+ months). All patients experienced TRAEs – Grade 3-4 TRAEs occurred in five (38%) patients, three (23%) of whom experienced diarrhea. No patients discontinued zanidatamab due to a TRAE and there were no treatment-related deaths. Zanidatamab plus chemotherapy ± bev demonstrated encouraging antitumor activity with a generally manageable safety profile as first-line treatment for patients with HER2-positive mCRC.

About Zanidatamab
Zanidatamab is an investigational dual HER2-targeted bispecific antibody that simultaneously binds to two distinct sites on HER2, known as biparatopic binding. This unique design and enhanced binding results in multiple mechanisms of action, including HER2 and HER3 signal blockade, removal of HER2 protein from the cell surface and enhanced immune effector functions, such as complement-dependent cytotoxicity (CDC), which leads to encouraging antitumor activity. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

The U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review of the Biologics License Application (BLA) for zanidatamab with a Prescription Drug User Fee Act (PDUFA) action date of November 29, 2024. Zanidatamab was also granted Breakthrough Therapy designation in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC) and given two Fast Track designations: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.

About Gastroesophageal Adenocarcinoma
Gastroesophageal adenocarcinoma (GEA) is the fifth most common cancer worldwide, and approximately 20% of patients have HER2–positive disease.1,2,3 HER2–positive GEA has high morbidity and mortality, and patients are urgently in need of new treatment options.

On September 16, 2024 GV20 Therapeutics, a clinical-stage AI-based next generation biotherapeutics company, reported presentation of clinical results from its Phase 1/2 study of GV20-0251 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 in Barcelona, Spain (Press release, GV20 Therapeutics, SEP 16, 2024, View Source [SID1234646674]).

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Dr. Kristopher Wentzel from The Angeles Clinic and Research Institute gave an oral presentation on the clinical data from the monotherapy dose escalation portion of the ongoing study of GV20-0251, a first-in-class antibody targeting the novel immune checkpoint IGSF8, in patients with advanced solid tumors (NCT05669430).

Key highlights from the presentation include:

Patient Population: The study enrolled 38 heavily pre-treated patients across six dose levels and two dosing schedules. The median age was 62 years, with a median of 4 prior lines of treatment.

Safety: GV20-0251 was well-tolerated across all dose levels (0.5 to 20 mg/kg) with no dose-limiting toxicities observed. Most of treatment-related adverse events were grade 1/2, with only one case of grade 3 pneumonitis reported.

Efficacy: Two confirmed partial responses were observed in 12 efficacy-evaluable metastatic cutaneous melanoma patients. Additionally, 14 of 29 efficacy-evaluable patients showed stable disease, including 4 with tumor shrinkage.

Pharmacokinetics: Dose-proportional pharmacokinetics with half-life around 25.6 days and full target occupancy on circulating T cells were observed at doses ≥ 3 mg/kg.
Click here to access the ESMO (Free ESMO Whitepaper) presentation.

"We are excited by these encouraging results for GV20-0251, which represent a significant milestone as the first clinical data for an AI-designed antibody against an AI-predicted target," said Dr. Shirley Liu, Co-founder and Chief Executive Officer of GV20 Therapeutics. "The favorable safety profile and preliminary efficacy signals, particularly in melanoma patients, support the potential of IGSF8 as a novel immune checkpoint target."

GV20-0251 is designed to enhance NK cell killing of malignant cells, upregulate dendritic cell antigen presentation, and increase T cell signaling. This mechanism of action may be particularly relevant for patients with antigen presentation-deficient tumors, which are often resistant to current immune checkpoint inhibitors.

The company is currently recruiting anti-PD1-relapsed and refractory cancer patients to be treated by GV20-0251 in combination with pembrolizumab to further evaluate the drug safety, pharmacokinetics, pharmacodynamics, and efficacy.

On September 16, 2024 Trishula Therapeutics, Inc., a clinical stage, privately held biotechnology company, reported final results from a Phase 1 trial of TTX-030, a potential first-in-class, anti-CD39 antibody, in patients with first-line metastatic pancreatic cancer (Press release, Trishula Therapeutics, SEP 16, 2024, View Source [SID1234646673]). Results were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 in Barcelona, Spain.

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"The Phase 1 results demonstrated a strong median overall survival in patients with metastatic pancreatic cancer following treatment with TTX-030 combinations as well as marked benefit in those with high levels of tumor HLA-DQ biomarker expression," said Anil Singhal, Chief Executive Officer of Trishula Therapeutics. "These findings have led to our currently enrolling global, randomized Phase 2 ELTIVATE study with results expected in 2026."

The Phase 1 trial evaluated TTX-030 in combination with gemcitabine/nab-paclitaxel, with or without budigalimab (an investigational anti-PD-1 antibody), as first-line treatment for pancreatic adenocarcinoma. In the efficacy-evaluable population (n=57) consisting of 92% first-line metastatic and 8% locally advanced nonresecetable patients, the objective response rate (ORR) was 30%, with 3 complete responses; the median progression free survival (mPFS) was 7.5 months (95%CI 5.2, 9.4); and median overall survival was 19.1 months (9.8, NR). Analysis of pre-treatment tumor biopsies identified a subset of patients with a high expression of an immune-associated biomarker, HLA-DQ (HLA-DQhigh) and favorable clinical outcomes with TTX-030 combinations. Of the 28 HLA-DQhigh patients, the ORR was 46%, mPFS was 9.6 months (95% CI 3.9, 11.8), and mOS of 21.9 months (9.8, NR).

Both treatment combinations were well-tolerated, with only five patients (8%) discontinuing treatment due to adverse events (AEs). The most frequent AEs were those expected from the standard of care chemotherapy backbone without an increase in frequency or severity.

"Prior evaluation of immune checkpoint treatment has demonstrated limited benefit in this patient population and new approaches are needed. These results are very encouraging, especially in the biomarker high patients and warrant further investigation of TTX-030 for patients with advanced pancreatic cancer," said Zev Wainberg, MD, Professor of Medicine, UCLA.

TTX-030 is currently being evaluated as first-line treatment for metastatic pancreatic adenocarcinoma in the global Phase 2 ELTIVATE trial (NCT06119217) that is randomizing approximately 180 patients into three study arms: TTX-030 and chemotherapy (gemcitabine and nab-paclitaxel); TTX-030 plus budigalimab and chemotherapy; or chemotherapy alone. The primary endpoint of the trial is progression-free survival (PFS) in a biomarker-enriched (HLA-DQhigh) population. Secondary endpoints include PFS in the overall population, safety, objective response rate, duration of response and overall survival. Further information on the study can be found at (clinicaltrials.gov link).

About TTX-030

TTX-030 is a potential first-in-class, anti-CD39 antibody designed to inhibit the activity of CD39, an enzyme that converts adenosine triphosphate (ATP) to adenosine monophosphate (AMP), the initial step in the generation of adenosine in the tumor microenvironment. TTX-030 prevents the formation of immune-suppressive extracellular adenosine and maintains high levels of immune-activating extracellular ATP, stimulating dendritic and myeloid-derived cells promoting both innate and adaptive anti-tumor immunity.

Trishula is continuing to develop TTX-030 in collaboration with AbbVie Inc.

On September 16, 2024 Aethlon Medical, Inc. (Nasdaq: AEMD), a medical therapeutic company focused on developing products to treat cancer and life-threatening infectious diseases, reported that the Cancer Clinical Trial Unit at Royal Adelaide Hospital was activated on September 10, 2024 to begin screening and enrolling patients in its safety, feasibility and dose-finding clinical trial of the Hemopurifier in patients with solid tumors who have stable or progressive disease during anti-PD-1 monotherapy treatment, such as Keytruda (pembrolizumab) or Opdivo (nivolumab) (AEMD-2022-06 Hemopurifier Study) (Press release, Aethlon Medical, SEP 16, 2024, View Source [SID1234646672]). The trial will be conducted by Prof. Michael Brown and his staff at the Cancer Clinical Trials Unit, CALHN, Royal Adelaide Hospital in Australia.

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The activation follows the previously announced approval by the Human Research Ethics Committee at Central Adelaide Local Health Network on June 13, 2024, and the Research Governance office at Royal Adelaide Hospital, on September, 3 2024, as well as the notification of the Therapeutic Good Administration (TGA) and completion of a Site Initiation Visit on September 9, 2024.

"The activation of the investigative site at the Royal Adelaide Hospital marks a significant milestone for Aethlon, allowing the site to screen and enroll patients in this important clinical trial," stated Steven LaRosa, MD, Chief Medical Officer of Aethlon Medical. "We look forward to working closely with Prof. Brown and his staff, and with our Contract Research Organizations (CROs), NAMSA and ReSQ Clinical Research, to begin enrollment and data collection. Going forward, we plan to activate a second site in Australia and also expect to receive an Ethics Committee approval for a clinical site in India."

Currently, only approximately 30% of patients who receive pembrolizumab or nivolumab will have lasting clinical responses to these agents. Extracellular vesicles (EVs) produced by tumors have been implicated in the spread of cancers as well as the resistance to anti-PD-1 therapies. The Aethlon Hemopurifier has been designed to bind and remove these EVs from the bloodstream, which may improve therapeutic response rates to anti-PD-1 antibodies. In preclinical studies, the Hemopurifier has been shown to reduce the number of exosomes from the plasma of cancer patient samples.

The primary endpoint of the approximately 18-patient, safety, feasibility and dose-finding trial is the incidence of adverse events and clinically significant changes in safety lab tests of Hemopurifier treated patients with solid tumors with stable or progressive disease at different treatment intervals, after a two-month run in period of PD-1 antibody, Keytruda or Opdivo monotherapy. Patients who do not respond to the therapy will be eligible to enter the Hemopurifier period of the study where sequential cohorts will receive 1, 2 or 3 Hemopurifier treatments during a one-week period. In addition to monitoring safety, the study is designed to examine the number of Hemopurifier treatments needed to decrease the concentration of EVs and whether these changes in EV concentrations improve the body’s own natural ability to attack tumor cells. These exploratory central laboratory analyses are expected to inform the design of a subsequent efficacy and safety, Premarket Approval (PMA), study required by regulatory agencies.

On September 16, 2024 AVEO Oncology, an LG Chem company ("AVEO"), reported that the TiNivo-2 Phase 3 clinical trial results in patients with advanced metastatic renal cell carcinoma (RCC) whose tumors had progressed following prior ICI treatment were presented at the 2024 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) congress September 13-17 in Barcelona, Spain (Press release, AVEO, SEP 16, 2024, View Source [SID1234646671]). Additionally, a follow up exploratory analysis from TIVO-3, FOTIVDA’s pivotal trial, was also presented during the conference.

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The TiNivo-2 clinical trial was designed to evaluate the treatment of FOTIVDA, a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), in combination with nivolumab, a PD-1 inhibitor, versus FOTIVDA as a single agent therapy to investigate the benefit of ICI challenge in a relapsed refractory setting.

Toni Choueiri, M.D., Director of the Lank Center for Genitourinary Oncology, Director of the Kidney Cancer Center at Dana-Farber Cancer Institute, Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School, and lead investigator presented the first analysis of the TiNivo-2 study results at ESMO (Free ESMO Whitepaper). The addition of nivolumab to FOTIVDA (0.89 mg) following prior immunotherapy did not enhance efficacy over FOTIVDA (1.34 mg) alone (hazard ratio 1.10 [95% confidence interval, 0.84-1.43; P=0.49]); as such the study did not meet its primary endpoint. In pre-planned analyses of the FOTIVDA control arm, a 9.2 month median progression free survival (PFS) was observed for patients that received FOTIVDA monotherapy as second line and for patients immediately following ICI combination therapy; the experimental arm (nivolumab plus tivozanib) had a 7.3 month median PFS in the second line and a 7.4 month median PFS for patients immediately following ICI combination therapy.

The TiNivo-2 study results add to the existing body of data in RCC suggesting there is no clinical benefit derived from rechallenging patients with immunotherapy beyond progression on previous ICIs.

"We are truly grateful for the patients who participated in TiNivo-2 so that we can continue to make evidence-based advancements in RCC treatment and patient care," says Michael P. Bailey, AVEO Oncology Chief Executive Officer and President. "We are excited to share the comprehensive TiNivo-2 dataset with the oncology community; these data provide additional support on the use of FOTIVDA as an option in the second line following frontline immunotherapy combination treatment."

Dr. Choueiri comments, "The PFS results in the intent-to-treat population demonstrate the activity of tivozanib in the 2nd and 3rd lines following front line immunotherapy. The safety results were also consistent with the safety profile observed in TIVO-3."

In conjunction with the scientific presentation, the TiNivo-2 data were simultaneously published in the prestigious journal, The Lancet.

In addition to the TiNivo-2 data presentation, an exploratory long-term follow up analysis from the TIVO-3 study was presented by Dr. Miguel Zugman of the City of Hope Comprehensive Cancer Center at ESMO (Free ESMO Whitepaper) 2024. Although the post hoc analysis did not reach statistical significance, the data indicates that tivozanib trended toward improved OS compared to sorafenib, in the subset of patients previously treated with checkpoint inhibitors. The OS hazard ratio in the checkpoint inhibitor-treated subset was 0.69 (95% confidence interval, 0.43-1.11) favoring tivozanib.

TiNivo-2 Clinical Trial Details
Phase 3 clinical trial designed to evaluate the safety and efficacy of tivozanib in combination with nivolumab, as compared to tivozanib as a monotherapy, in RCC patients whose tumors have progressed following prior ICI therapy.

TIVO-3 Clinical Trial Details
TIVO-3 was a Phase 3, global, open-label, parallel-arm study comparing the safety and efficacy of FOTIVDA versus sorafenib in patients with relapsed refractory advanced RCC whose disease progressed with two or three prior systemic regimens including at least one VEGFR TKI.

About FOTIVDA
FOTIVDA is an oral, next-generation VEGFR TKI. It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021, for the treatment of adult patients with relapsed or refractory advanced RCC following two or more prior systemic therapies, based on data from the TIVO-3 trial comparing FOTIVDA to sorafenib. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner Recordati UK Ltd. for the treatment of adult patients with advanced RCC. FOTIVDA was discovered by Kyowa Kirin.

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS

Hypertension was reported in 45% of patients (22% ≥ Grade 3). Hypertensive crises were reported in 0.8% of patients. Do not initiate FOTIVDA in patients with uncontrolled hypertension. Monitor for hypertension and treat as needed. Reduce the FOTIVDA dose for persistent hypertension not controlled by anti-hypertensive medications. Discontinue FOTIVDA for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Cardiac failures were reported in 1.6% of patients (1% ≥ Grade 3); 0.6% of events were fatal. Monitor for signs or symptoms of cardiac failure during treatment with FOTIVDA. Manage with dose interruption, dose reduction, or discontinuation.

Cardiac ischemia were reported in 3.2% of patients; 0.4% of events were fatal. Arterial thromboembolic events were reported in 2.0% of patients, including death due to ischemic stroke (0.1%). Closely monitor patients at risk for, or who have a history of these events. Discontinue FOTIVDA in patients who develop severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thrombotic Events (VTE) were reported in 2.4% of patients, including 0.3% fatal events. Closely monitor patients who are at increased risk for these events. Discontinue in patients who develop serious VTEs.

Hemorrhagic Events were reported in 11% of patients; 0.2% of events were fatal. Use FOTIVDA with caution in patients who are at risk for or who have a history of bleeding.

Proteinuria was reported in 8% of patients (2% = Grade 3). Monitor during treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or interrupt treatment. Discontinue in patients who develop nephrotic syndrome.

Gastrointestinal (GI) Perforation including fatal cases, has been reported in patients receiving FOTIVDA. Monitor for symptoms of GI perforation or fistula formation periodically throughout treatment with FOTIVDA. Permanently discontinue FOTIVDA in patients who develop severe or life-threatening GI perforation.

Thyroid Dysfunction events were reported in 11% of patients (0.3% ≥ Grade 3). Monitor thyroid function before and during treatment with FOTIVDA.

Wound Healing Complications: Withhold FOTIVDA for at least 24 days prior to elective surgery and do not administer for at least 2 weeks after major surgery and until adequate wound healing is observed.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) can occur with FOTIVDA. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue if signs or symptoms of RPLS occur.

Embryo-fetal Toxicity: FOTIVDA can cause fetal harm. Advise patients of the potential risk to a fetus, to avoid becoming pregnant and to use contraception during treatment and for one month after the last dose of FOTIVDA. Advise males with female partners of reproductive potential to use effective contraception during treatment and for one month after the last dose of FOTIVDA.

Allergic Reaction to Tartrazine: FOTIVDA 0.89 mg capsule contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

Common adverse reactions include fatigue/asthenia, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis.

Serious adverse reactions include bleeding (3.5%), venous thromboembolism (3.5%), arterial thromboembolism (2.9%), acute kidney injury (2.3%), and hepatobiliary disorders (2.3%).

DRUG INTERACTIONS

Avoid coadministration with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Advise women not to breastfeed during treatment and for at least 1 month after the last dose.

The recommended dosage for patients with end-stage renal disease has not been established.

Reduce the FOTIVDA dose for patients with moderate hepatic impairment. The recommended dosage in patients with severe hepatic impairment has not been established.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information for FOTIVDA (tivozanib).