NeoSphere, TRYPHAENA, and CLEOPATRA clinical trial designs
Learn more about the trial designs, endpoints, and patient
demographics of each trial
Neoadjuvant PERJETA and Herceptin combination-based treatment was
studied in two separate trials, NeoSphere and TRYPHAENA
NeoSphere: A multicenter, randomized, open-label Phase II clinical
trial evaluating efficacy and safety of PERJETA-based neoadjuvant therapy1,12*
FEC=5-fluorouracil, epirubicin, and cyclophosphamide.
*NeoSphere is referred to as “Study 2” in the full PERJETA Prescribing Information.1
†Randomization stratified by breast cancer type (operable, locally advanced, or inflammatory) and estrogen receptor (ER) or progesterone receptor (PR) status ([ER+ and/or PR+] vs [ER- and PR-]).1
Treatment cycles were received every 3 weeks. During the neoadjuvant period, all patients received 4 cycles of their respective therapies. PERJETA dosing: 840 mg loading dose, 420 mg for subsequent 3 cycles; Herceptin dosing: 8 mg/kg loading dose, 6 mg/kg for subsequent 3 cycles (administered to complete 1 year of treatment); Docetaxel dosing: 75 mg/m2 every 3 weeks for 4 cycles. Docetaxel dose could be escalated to 100 mg/m2 at investigator’s discretion if initial dose was well tolerated. FEC dosing: 5-fluorouracil (600 mg/m2), epirubicin (90 mg/m2), and cyclophosphamide (600 mg/m2) every 3 weeks for 3 cycles.1
NeoSphere trial endpoints included pCR and safety
- Primary endpoint: pCR in the breast (ypT0/is)1
- ypT0/is=no invasive cells in the breast by microscopic examination at surgery, in situ lesions permitted12
- Additional pCR
endpoint (FDA-preferred): pCR in the breast and nodes (ypT0/is ypN0)1
- ypT0/is ypN0=the absence of invasive cancer in the breast and lymph nodes, in situ lesions permitted
- Select secondary endpoints included safety12
Patient demographics in NeoSphere1
Demographics were balanced across treatment arms.
‡Data missing for 1 patient.
Select Important Safety Information: Left Ventricular Dysfunction
Decreases in left ventricular ejection fraction (LVEF) have been reported with drugs that block HER2 activity, including PERJETA. Assess LVEF prior to initiation of PERJETA and at regular intervals (eg, every 3 months in the metastatic setting and every 6 weeks in the neoadjuvant setting) during treatment to ensure that LVEF is within the institution’s normal limits. If LVEF is <45%, or is 45% to 49% with a 10% or greater absolute decrease below the pretreatment value, withhold PERJETA and trastuzumab and repeat LVEF assessment within approximately 3 weeks. Discontinue PERJETA and trastuzumab if the LVEF has not improved or has declined further, unless the benefits for the individual patient outweigh the risks.
An additional open-label Phase II trial of neoadjuvant PERJETA-based treatment1,13§
- 225 patients with locally advanced, operable, or inflammatory HER2+ breast cancer (T2-4d)
- Designed primarily to assess cardiac safety; all arms included PERJETA
- All treatments administered in 3-week cycles
TCH=docetaxel, carboplatin, and Herceptin.
§TRYPHAENA is referred to as “Study 3” in the full PERJETA Prescribing Information.1
‖ Randomization stratified by breast cancer type (operable, locally advanced, or inflammatory) and estrogen receptor (ER) or progesterone receptor (PR) status ([ER+ and/or PR+] vs [ER- and PR-]). 1
Treatment cycles were received every 3 weeks. PERJETA dosing: 840 mg loading dose, 420 mg for subsequent cycles; Herceptin dosing: 8 mg/kg loading dose, 6 mg/kg for subsequent cycles (administered to complete 1 year of treatment); docetaxel dosing: 75 mg/m2 each cycle, escalated to 100 mg/m 2 at investigator’s discretion if initial dose was well tolerated (not escalated in the PERJETA + TCH arm); carboplatin dosing: AUC 6; FEC dosing: 5-fluorouracil (500 mg/m 2 ), epirubicin (100 mg/m 2 ), and cyclophosphamide (600 mg/m 2 ) every 3 weeks for 3 cycles. 1
TRYPHAENA endpoints included cardiac safety and tolerability
- Cardiac safety and tolerability during neoadjuvant
- Incidence of symptomatic left ventricular systolic dysfunction (LVSD)
- Decline in LVEF of ≥10% from baseline to <50%
Select secondary endpoints1,13
- pCR in breast (ypT0/is) assessed at surgery
- Additional pCR endpoint (FDA-preferred): pCR in breast and nodes (ypT0/is ypN0) assessed at surgery
ypT0/is=no invasive cells in the breast by
microscopic examination at surgery, in situ lesions permitted.13
ypT0/is ypN0=the absence of invasive cancer in the breast and lymph nodes, in situ lesions permitted.1
Patient demographics in TRYPHAENA14
Demographics were balanced across treatment arms.
Select Important Safety Information: Infusion-Associated Reactions
PERJETA has been associated with infusion reactions. Observe patients closely for 60 minutes after the first infusion and for 30 minutes after subsequent infusions of PERJETA. If a significant infusion-related reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies. Monitor patients carefully until complete resolution of signs and symptoms. Consider permanent discontinuation in patients with severe infusion reactions.
CLEOPATRA evaluated 1L PERJETA and Herceptin combination-based
treatment for patients with HER2+ metastatic breast cancer
A multicenter, randomized, double-blind, placebo-controlled Phase
III trial of first-line (1L) PERJETA-based treatment
All therapies administered every 3 weeks.
PERJETA dosing: 840 mg loading dose over 60 minutes; 420 mg over 30-60 minutes for subsequent infusions. Herceptin dosing: 8 mg/kg loading dose over 90 minutes; 6 mg/kg over 30-90 minutes for subsequent infusions. Docetaxel dosing: 75 mg/m² over 60 minutes for ≥6 cycles. Dose could be decreased by 25% due to toxicity or increased to 100 mg/m² in those patients who could tolerate this dose; <6 cycles were allowed for unacceptable toxicity.1,2
HER2 overexpression was defined as IHC 3+ or FISH amplification ratio ≥2.0. IHC 3+ is defined as uniform, intense membrane staining in >10% of tumor cells. Patients with a ≥12-month disease-free interval following adjuvant or neoadjuvant therapy, or one prior hormonal treatment for MBC were eligible for enrollment.
*Stratified by prior treatment status (de novo or prior adjuvant/neoadjuvant therapy) and geographic region.
CLEOPATRA trial endpoints included PFS, OS, and safety
- Progression-free survival (PFS; as assessed by an independent
review facility [IRF]), defined as time from randomization to
documented progressive disease as determined by RECIST,†
Select secondary endpoints1
- Overall survival (OS)
- Investigator-assessed PFS
- Objective response rate (ORR)
- Duration of response (DoR)
†RECIST=response evaluation criteria in solid tumors,
Patient demographics in CLEOPATRA2
ECOG=Eastern Cooperative Oncology Group;
ER=estrogen receptor; PR=progesterone receptor;
IHC=immunohistochemistry; FISH=fluorescence in situ
†Race or ethnic group was determined by the investigator. The category of “Other” includes American Indian and Alaska Native.
‡Patients may have received more than one form of adjuvant or neoadjuvant chemotherapy.
Select Important Safety Information: Hypersensitivity Reactions/Anaphylaxis
Patients should be observed closely for hypersensitivity reactions. Severe hypersensitivity, including anaphylaxis, has been observed in clinical trials with treatment of PERJETA. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients.