Behind KANJINTI®

A robust biosimilars program

KANJINTI® IS A PROVEN BIOSIMILAR TO HERCEPTIN®* BASED ON A TOTALITY OF EVIDENCE1-3

Biosimilar Development Steps Biosimilar Development Steps

FDA-approved for all Herceptin® indications5,6

eBC = early breast cancer.

*EU-sourced Herceptin® was used in the LILAC study. The KANJINTI® clinical pharmacokinetic (PK) study demonstrated equivalence between EU- and US-sourced Herceptin® and KANJINTI®.

Conducting biosimilar studies in this sensitive early breast cancer (eBC) population provides scientific evidence supporting extrapolation to less sensitive populations.1,7

  • BIOSIMILARITY PROVEN IN A COMPARATIVE CLINICAL STUDY

    KANJINTI® WAS PROVEN BIOSIMILAR TO HERCEPTIN®

    LILAC study results supported no clinically meaningful differences between KANJINTI® and Herceptin®*

    Use of trastuzumab in the neoadjuvant setting is not an approved indication in the product label
    for KANJINTI® or Herceptin®. The selection of the patient population was appropriate to support demonstration of no clinically meaningful differences between KANJINTI® and Herceptin®.*1,5,6

    Study design and key considerations1

    • Study population: Patients with early breast cancer (eBC) in the neoadjuvant setting.
      • eBC is a homogenous and sensitive population for assessing any clinically meaningful differences between the two products.
    • Study design: A comparative, randomized equivalence trial between KANJINTI® and Herceptin® in patients with HER2+ eBC (N = 725).
      • Prior to surgery, patients received epirubicin (90 mg/m2) + cyclophosphamide (600 mg/m2) once every 3 weeks (Q3W) for 4 cycles. Patients were then randomized to KANJINTI®
        or Herceptin®, both administered with paclitaxel (175 mg/m2), at a loading dose of 8 mg/kg, then 6 mg/kg Q3W prior to surgery.
      • Following surgery, patients in the KANJINTI® arm continued treatment with KANJINTI®; patients in the Herceptin® arm were randomly assigned to either Herceptin® or KANJINTI®. Treatment continued in all 3 arms Q3W for
        ≤ 1 year from the initial neoadjuvant dose.
    • Coprimary endpoints: Risk difference (RD) and risk ratio (RR) of pathologic complete response (pCR) by local laboratory review evaluated based on the neoadjuvant portion of the study.

    CI = confidence interval.

    *EU-sourced Herceptin® was used in the LILAC study. The KANJINTI® clinical pharmacokinetic (PK) study demonstrated equivalence between EU- and US-sourced Herceptin® and KANJINTI®.

    Central laboratory review was performed to reduce the pathologic variability at the local level.

    PATHOLOGICAL COMPLETE RESPONSE (pCR) RATES BY CENTRAl LABORATORY REVIEW1,*

    chart rd-rr
    pcr_desk

    pCR rates by local laboratory review demonstrated similar results1

    • In the neoadjuvant setting, 48% with KANJINTI® (95% CI, 43%–53%; n = 172/358) and 41% with Herceptin® (95% CI, 35%–46%; n = 137/338) achieved pCR in both breast tissue and axillary lymph nodes.
    • Coprimary endpoints: RD (90% Cl) = 7.3% (1.2%–13.4%); RR (90% Cl) = 1.188 (1.033–1.366).

    CI = confidence interval.

    *EU-sourced Herceptin® was used in the LILAC study. The KANJINTI® clinical pharmacokinetic (PK) study demonstrated equivalence between EU- and US-sourced Herceptin® and KANJINTI®.

    Central laboratory review was performed to reduce the pathologic variability at the local level.


    KANJINTI® IS THE FIRST AND ONLY HERCEPTIN®* BIOSIMILAR WITH SINGLE-TRANSITION STUDY DATA IN THE eBC SETTING1,5,8-13

    Single transition

    Designed to provide robust data by:

    • Reinforcing clinical similarity of KANJINTI® and Herceptin®*§
    • Reflecting a real-world clinical scenario of transitioning patients from Herceptin®* to KANJINTI®14
    • Providing safety and immunogenicity data for up to 1 year of treatment

    *EU-sourced Herceptin® was used in the LILAC study. The KANJINTI® clinical pharmacokinetic (PK) study demonstrated equivalence between EU- and US-sourced Herceptin® and KANJINTI®.

    §Initial dose of 8 mg/kg IV then 6 mg/kg IV for remaining cycles.

    ** Total of up to 1 year from the first day of KANJINTI®/Herceptin® administered in the neoadjuvant phase.

    ††Lumpectomy or mastectomy with sentinel or axillary lymph node dissection.

    SIMILAR SAFETY AND IMMUNOGENICITY, EVEN IN PATIENTS WHO TRANSITIONED TO KANJINTI®

    No new or different adverse events (AEs) compared with Herceptin® were observed1

    adverse events OF INTEREST (EOI)1 greater than or equal to GRADE 3

    CI = confidence interval.

    *EU-sourced Herceptin® was used in the LILAC study. The KANJINTI® clinical pharmacokinetic (PK) study demonstrated equivalence between EU- and US-sourced Herceptin® and KANJINTI®.

    Central laboratory review was performed to reduce the pathologic variability at the local level.

    neoadjuvant phase adjuvant phase neoadjuvant and adjuvant chart

    Safety was assessed in both neoadjuvant and adjuvant settings to support biosimilarity. Only treatment-emergent AEs are summarized. For each category, subjects are included only once, even if they experienced multiple events in that category. Following surgery, 171 patients underwent a single transition from Herceptin® to KANJINTI® to further evaluate safety and immunogenicity.

    Transitioned to KANJINTI®
    • Antidrug antibody formation was low (≤ 2%) in all study arms. No patients developed neutralizing antibodies.1
    • No evidence of increased cardiotoxicity for KANJINTI®—median LVEF values did not change in any study arm over the full course of the study.1

    LVEF = left ventricular ejection fraction.

  • Bioequivalence shown in clinical pharmacokinetic studies

    Pharmacokinetics were bioequivalent to Herceptin® in healthy
    subjects2,3

    Mean serum concentration-time profiles for KANJINTI®, Herceptin® (US), and Herceptin® (EU) IN HUman Volunteers2

    KANJINTI® Pharmacokinetic – Mean Serum Concentration time
Profiles KANJINTI® Pharmacokinetic – Mean Serum Concentration time
Profiles

    A randomized, single-blind, single-dose, 3-arm, parallel-group study to determine the pharmacokinetic equivalence of KANJINTI® and Herceptin® in healthy adult males. The primary objective was to evaluate bioequivalence of KANJINTI® and Herceptin® in terms of AUCinf and Cmax (equivalence criteria: 90% CI for geometric mean ratio within 0.80–1.25).2

    • The mean serum concentration-time profiles were similar between treatments over the entire course of sampling.2
    • Peak concentrations were observed approximately 1.5 to 5 hours after the start of the infusion.2

    NO DIFFERENCES IN CLINICAL PK PROFILE
    BETWEEN KANJINTI® AND HERCEPTIN®2,3

    AUCinf = area under the concentration curve versus time from zero to infinity; Cmax = maximum serum concentration; PK = pharmacokinetic.

  • Comparable nonclinical antitumor activity data

    Similar antitumor activity to HERCEPTIN® in XENOGRAFT models3

    Antitumor activity in breast cancer xenograft study

    KANJINTI® Nonclinical Data – Antitumor Activity in Breast
Cancer Xenograft Study KANJINTI® Nonclinical Data – Antitumor Activity in Breast
Cancer Xenograft Study

    NOD/SCID mice were injected orthotopically with BT-474 human breast tumor cells that naturally overexpress HER2 receptors (8 x 106 cells per mouse). After 21 days, treatment with vehicle control, KANJINTI®, or Herceptin® was administered twice weekly by IV for 19 days. Tumor sizes were measured twice per week until day 56.

    Antitumor activity in Gastric cancer xenograft study

    KANJINTI® Nonclinical Data – Antitumor Activity in Gastric
Cancer Xenograft Study KANJINTI® Nonclinical Data – Antitumor Activity in Gastric
Cancer Xenograft Study

    CD-1 nude mice were injected subcutaneously with NCI-N87 gastric tumor cells (5 x 106 cells per mouse). When average tumor size reached ~100 mm3, vehicle control, KANJINTI®, or Herceptin® was administered twice weekly by intraperitoneal injection for 19 days. Tumor sizes were measured three times per week until day 35.

    IN VIVO STUDIES PROVIDE ADDITIONAL
    EVIDENCE TO SUPPORT BIOSIMILARITY8

    BT-474 = metastatic human breast cancer cells; HER2 = human epidermal growth factor receptor 2; IV = intravenous; NCI-N87 = human gastric cancer cells; NOD/SCID = nonobese diabetic/severe combined immune deficient.

  • ANALYTICAL (FOUNDATIONAL) STUDIES

    Analytical data can be summarized as similar with regard to: DNA sequence, monoclonal antibody protein structure, biological activity, purity, and stability.4

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