Results from FRESCO, the first pivotal trial for FRUZAQLA^® (fruquintinib)

FRESCO was a single-country (China), multicenter, randomized, double-blind, placebo-controlled phase 3 trial^1,2

FRESCO study design

FRESCO clinical trial design studying FRUZAQLA® + BSC vs placebo + BSC.

Inclusion criteria^1,2

Aged 18-75
ECOG PS 0‑1
Progression during or after prior treatment with fluoropyrimidine‑, oxaliplatin‑, or irinotecan‑based chemotherapy
No prior treatment with VEGFR inhibitor

Stratification²

Prior VEGF inhibitor therapy (yes vs no)
K-RAS mutational status (wild type vs mutant)

FRESCO was a robust clinical trial that included a population of patients who had received ≥2 prior lines of therapy^1,2

FRESCO patient characteristics^1,2

FRESCO patient characteristics for FRUZAQLA® + BSC vs placebo + BSC.

^aAll eligible patients had ECOG PS=0 or 1 (0=fully active, able to carry on all predisease activities without restriction; 1=restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature).²
^bReferred to cecum.²
^cIncluded 120 patients who had received bevacizumab (fruquintinib arm, 83; placebo arm, 37) and 5 patients who had received aflibercept (fruquintinib arm, 1; placebo arm, 4).²
^dCetuximab.²
^eNo patients received VEGFR inhibitors.²

OS: A significant overall survival (OS) benefit was observed with FRUZAQLA vs placebo

Median OS was improved by nearly 3 months for patients with previously treated mCRC^1,2

FRESCO: Overall survival (OS) in adult patients with previously treated metastatic colorectal cancer taking FRUZAQLA® + BSC vs placebo + BSC.

Rapid separation of OS curve beginning at Month 2^1,2

CI=confidence interval; HR=hazard ratio.

35 percent reduction in risk of death with FRUZAQLA® + BSC vs placebo + BSC.

OS Subgroups: OS benefit was consistent across most prespecified subgroups^2,3

FRESCO: Overall survival (OS) comparing FRUZAQLA® + BSC vs placebo + BSC across prespecified subgroups.

The FRESCO study was not powered to show significance in OS across these specified groups.

PFS: FRUZAQLA more than doubled median progression-free survival (PFS) vs placebo^1,2

PFS in patients with previously treated mCRC^1,2

FRESCO: Progression- free survival (PFS) in adult patients with previously treated metastatic colorectal cancer taking FRUZAQLA® + BSC vs placebo + BSC.

PFS curve had early and rapid separation that was evident at Month 1^1,2

Statistical significance is not implied. P value for the PFS analysis in FRESCO was not included due to lack of multiplicity adjustment for this analysis.¹

**More than half of patients treated with FRUZAQLA + BSC* achieved a stable disease control rate^1,2**

FRESCO: 62% disease control rate with FRUZAQLA® + BSC vs 12% with placebo + BSC.

The FRESCO study was not powered to show significance in disease control rate.

*Disease control was defined as a complete response, partial response, or stable disease for ≥8 weeks after randomization.²

PFS Subgroups: Consistent PFS benefit was demonstrated across all prespecified subgroups.

FRESCO-2: Progression free survival (PFS) comparing FRUZAQLA® + BSC vs placebo + BSC across prespecified subgroups.

The FRESCO study was not powered to show significance in PFS across these specified groups.

FRESCO Safety Profile

Discover the safety profile of FRUZAQLA from the FRESCO clinical trial.

Learn about the safety profile

FRESCO-2 Efficacy Results

Learn about the efficacy results from FRESCO-2, a global, double-blind, placebo-controlled study with a heterogenous patient population.

Explore trial data

FRESCO-2 Quality of Life Results

Learn more about how Quality of Life was measured in FRESCO-2.

Discover QoL data

2L=second-line; 3L=third-line; AR=adverse reaction; BSC=best supportive care; CI=confidence interval; ECOG PS=Eastern Cooperative Oncology Group performance status; EGFR=epidermal growth factor receptor; HR=hazard ratio; K-RAS=Kirsten rat sarcoma; OS=overall survival; PFS=progression-free survival. RAS=rat sarcoma; VEGF=Vascular endothelial growth factor; VEGFR= Vascular endothelial growth factor receptor.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension occurred in 49% of 911 patients with mCRC treated with FRUZAQLA, including Grade 3-4 events in 19%, and hypertensive crisis in three patients (0.3%). Do not initiate FRUZAQLA unless blood pressure is adequately controlled. Monitor blood pressure weekly for the first month and at least monthly thereafter as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue FRUZAQLA based on severity of hypertension.

Hemorrhagic Events including serious, fatal events can occur with FRUZAQLA. In 911 patients with mCRC treated with FRUZAQLA, 6% of patients experienced gastrointestinal hemorrhage, including 1% with a Grade ≥3 event and 2 patients with fatal hemorrhages. Permanently discontinue FRUZAQLA in patients with severe or life-threatening hemorrhage. Monitor the International Normalized Ratio (INR) levels in patients receiving anticoagulants.

Infections. FRUZAQLA can increase the risk of infections, including fatal infections. In 911 patients with mCRC treated with FRUZAQLA, the most common infections were urinary tract infections (6.8%), upper respiratory tract infections (3.2%) and pneumonia (2.5%); fatal infections included pneumonia (0.4%), sepsis (0.2%), bacterial infection (0.1%), lower respiratory tract infection (0.1%), and septic shock (0.1%). Withhold FRUZAQLA for Grade 3 or 4 infections, or worsening infection of any grade. Resume FRUZAQLA at the same dose when the infection has resolved.

Gastrointestinal Perforation occurred in patients treated with FRUZAQLA. In 911 patients with mCRC treated with FRUZAQLA, 1.3% experienced a Grade ≥3 gastrointestinal perforation, including one fatal event. Permanently discontinue FRUZAQLA in patients who develop gastrointestinal perforation or fistula.

Hepatotoxicity. FRUZAQLA can cause liver injury. In 911 patients with mCRC treated with FRUZAQLA, 48% experienced increased ALT or AST, including Grade ≥3 events in 5%, and fatal events in 0.2% of patients. Monitor liver function tests (ALT, AST, and bilirubin) before initiation and periodically throughout treatment with FRUZAQLA. Temporarily hold and then reduce or permanently discontinue FRUZAQLA depending on the severity and persistence of hepatotoxicity as manifested by elevated liver function tests.

Proteinuria. FRUZAQLA can cause proteinuria. In 911 patients with mCRC treated with FRUZAQLA, 36% experienced proteinuria and 2.5% of patients experienced Grade ≥3 events. Monitor for proteinuria before initiation and periodically throughout treatment with FRUZAQLA. For proteinuria ≥2g/24 hours, withhold FRUZAQLA until improvement to ≤Grade 1 proteinuria and resume FRUZAQLA at a reduced dose. Discontinue FRUZAQLA in patients who develop nephrotic syndrome.

Palmar-Plantar Erythrodysesthesia (PPE) occurred in 35% of 911 patients treated with FRUZAQLA, including 8% with Grade 3 events. Based on severity of PPE, withhold FRUZAQLA and then resume at the same or reduced dose.

Posterior Reversible Encephalopathy Syndrome (PRES), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in one of 911 patients treated with FRUZAQLA. Perform an evaluation for PRES in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue FRUZAQLA in patients who develop PRES.

Impaired Wound Healing. In 911 patients with mCRC treated with FRUZAQLA, 1 patient experienced a Grade 2 event of wound dehiscence. Do not administer FRUZAQLA for at least 2 weeks prior to major surgery. Do not administer FRUZAQLA for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of FRUZAQLA after resolution of wound healing complications has not been established.

Arterial Thromboembolic Events. In 911 patients with mCRC treated with FRUZAQLA, 0.8% of patients experienced an arterial thromboembolic event. Initiation of FRUZAQLA in patients with a recent history of thromboembolic events should be carefully considered. In patients who develop arterial thromboembolism, discontinue FRUZAQLA.

Allergic Reactions to FD&C Yellow No. 5 (Tartrazine) and No. 6 (Sunset Yellow FCF). FRUZAQLA 1 mg capsules contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. FRUZAQLA 1 mg contains FD&C Yellow No. 6 (sunset yellow FCF), which may cause allergic reactions.

Embryo-Fetal Toxicity. Based on findings in animal studies and its mechanism of action, FRUZAQLA can cause fetal harm when administered to pregnant women. Advise pregnant women of the potential risk to a fetus. Advise females of childbearing potential and males with female partners of childbearing potential to use effective contraception during treatment with FRUZAQLA and for 2 weeks after the last dose.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥20%) following treatment with FRUZAQLA included hypertension, palmar-plantar erythrodysesthesia (hand-foot skin reactions), proteinuria, dysphonia, abdominal pain, diarrhea, and asthenia.

DRUG INTERACTIONS

Avoid concomitant administration of FRUZAQLA with strong or moderate CYP3A inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during treatment with FRUZAQLA and for 2 weeks after the last dose.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-844-662-8532 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FRUZAQLA (fruquintinib) full Prescribing Information.

Results from FRESCO, the first pivotal trial for FRUZAQLA^® (fruquintinib)

FRESCO was a single-country (China), multicenter, randomized, double-blind, placebo-controlled phase 3 trial^1,2

FRESCO study design

FRESCO was a robust clinical trial that included a population of patients who had received ≥2 prior lines of therapy^1,2

FRESCO patient characteristics^1,2

OS: A significant overall survival (OS) benefit was observed with FRUZAQLA vs placebo

Median OS was improved by nearly 3 months for patients with previously treated mCRC^1,2

OS Subgroups: OS benefit was consistent across most prespecified subgroups^2,3

PFS: FRUZAQLA more than doubled median progression-free survival (PFS) vs placebo^1,2

PFS in patients with previously treated mCRC^1,2

**More than half of patients treated with FRUZAQLA + BSC* achieved a stable disease control rate^1,2**

PFS Subgroups: Consistent PFS benefit was demonstrated across all prespecified subgroups.

FRESCO Safety Profile

FRESCO-2 Efficacy Results

FRESCO-2 Quality of Life Results

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONS

INDICATION

FRESCO was a single-country (China), multicenter, randomized, double-blind, placebo-controlled phase 3 trial1,2

FRESCO study design

FRESCO was a robust clinical trial that included a population of patients who had received ≥2 prior lines of therapy1,2

FRESCO patient characteristics1,2

OS: A significant overall survival (OS) benefit was observed with FRUZAQLA vs placebo

Median OS was improved by nearly 3 months for patients with previously treated mCRC1,2

OS Subgroups: OS benefit was consistent across most prespecified subgroups2,3

PFS: FRUZAQLA more than doubled median progression-free survival (PFS) vs placebo1,2

PFS in patients with previously treated mCRC1,2

More than half of patients treated with FRUZAQLA + BSC* achieved a stable disease control rate1,2

PFS Subgroups: Consistent PFS benefit was demonstrated across all prespecified subgroups.

FRESCO Safety Profile

FRESCO-2 Efficacy Results

FRESCO-2 Quality of Life Results

IMPORTANT SAFETY INFORMATION AND INDICATION

FRESCO was a single-country (China), multicenter, randomized, double-blind, placebo-controlled phase 3 trial^1,2

FRESCO was a robust clinical trial that included a population of patients who had received ≥2 prior lines of therapy^1,2

FRESCO patient characteristics^1,2

Median OS was improved by nearly 3 months for patients with previously treated mCRC^1,2

OS Subgroups: OS benefit was consistent across most prespecified subgroups^2,3

PFS: FRUZAQLA more than doubled median progression-free survival (PFS) vs placebo^1,2

PFS in patients with previously treated mCRC^1,2

**More than half of patients treated with FRUZAQLA + BSC* achieved a stable disease control rate^1,2**