Libtayo

LIBTAYO is a programmed death receptor-1 (PD-1) blocking antibody indicated:

• for the treatment of adult patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation. (
  1.1 Cutaneous Squamous Cell Carcinoma

  LIBTAYO is indicated for the treatment of adult patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.

  LIBTAYO is indicated for the adjuvant treatment of adult patients with CSCC at high risk of recurrence

  [see Clinical Studies (14.1)]

  after surgery and radiation

  .
  )
• for the adjuvant treatment of adult patients with CSCC at high risk of recurrence after surgery and radiation. (
  1.1 Cutaneous Squamous Cell Carcinoma

  LIBTAYO is indicated for the treatment of adult patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.

  LIBTAYO is indicated for the adjuvant treatment of adult patients with CSCC at high risk of recurrence

  [see Clinical Studies (14.1)]

  after surgery and radiation

  .
  ,
  14.1 Cutaneous Squamous Cell Carcinoma (CSCC)

  Advanced CSCC

  The efficacy of LIBTAYO in patients with metastatic (nodal or distant) cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who were not candidates for curative surgery or curative radiation was evaluated in two open-label, multi-center, non-randomized, multicohort studies: Study 1423 (NCT02383212) and Study 1540 (NCT02760498). Both studies excluded patients with autoimmune disease that required systemic therapy with immunosuppressant agents within 5 years; history of solid organ transplant; prior treatment with anti–PD-1/PD-L1 blocking antibodies or other immune checkpoint inhibitor therapy; infection with HIV, hepatitis B or hepatitis C; or ECOG PS ≥2.

  Patients received LIBTAYO 3 mg/kg intravenously every 2 weeks for up to 48 weeks in Study 1423 or up to 96 weeks (Groups 1 and 2), or 350 mg every 3 weeks for up to 54 weeks (Group 3) in Study 1540. Treatment continued until progression of disease, unacceptable toxicity, or completion of planned treatment. Tumor response assessments were performed every 8 or 9 weeks. The major efficacy outcome measures were confirmed objective response rate (ORR), defined as complete response (CR) plus partial response (PR) as assessed by independent central review (ICR), and ICR-assessed duration of response (DOR). For patients with mCSCC without externally visible target lesions, ORR was determined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). For patients with externally visible target lesions (laCSCC and mCSCC), ORR was determined by a composite endpoint that integrated ICR assessments of radiologic data (RECIST 1.1) and digital medical photography (WHO criteria).

  Study 1540

  In the efficacy analysis of 193 patients with advanced CSCC enrolled in Study 1540 who received LIBTAYO at either 3 mg/kg every 2 weeks or 350 mg every three weeks, 115 had mCSCC and 78 had laCSCC. The median age was 72 years (38 to 96 years); 83% were male; 97% were White, 2% were Asian, 1% were Black or African American, and 1% were race unknown; 45% had ECOG PS 0 and 55% had ECOG PS 1; 34% received at least one prior anti-cancer systemic therapy; 81% received prior cancer-related surgery; and 68% received prior radiotherapy. Among patients with mCSCC, 77% had distant metastases and 23% had only nodal metastases.

  For the responding patients presented in Table 13 below, the median time to response was 2.1 months (range: 1.7 to 22.8 months).

  Efficacy results based on the final analysis of Study 1540 are presented in Table 13.

  Table 13: Efficacy Results for Study 1540 in Advanced CSCC

  Efficacy EndpointsMedian duration of follow up: mCSCC 3 mg/kg every 2 weeks: 18.5 months; laCSCC 3 mg/kg every 2 weeks: 15.5 months; mCSCC 350 mg every 3 weeks: 17.3 months; combined CSCC: 15.7 months	Metastatic CSCC LIBTAYO 3 mg/kg every 2 weeks (Group 1)	Locally Advanced CSCC LIBTAYO 3 mg/kg every 2 weeks (Group 2)	Metastatic CSCC LIBTAYO 350 mg every 3 weeks (Group 3)	Combined CSCC
  	N = 59	N = 78	N = 56	N = 193
  CI: confidence interval; NR: not reached
  Confirmed Objective Response Rate (ORR) (%)
  ORR (95% CI)	51 (37, 64)	45 (34, 57)	46 (33, 60)	47 (40, 54)
  Complete response rateOnly includes patients with complete healing of prior cutaneous involvement; laCSCC patients in Study 1540 required biopsy to confirm CR	20	13	20	17
  Partial response rate	31	32	27	30
  Duration of Response (DOR)
  Number of Responders	N = 30	N = 35	N = 26	N = 91
  Median DOR in monthsBased on Kaplan-Meier estimate(Range)	NR (2.8 – 38.9)	42 (1.9 – 54.6)	41 (4.2 – 46.3)	41 (1.9 – 54.6)
  Patients with observed DOR ≥6 months, n (%)The numerator includes the number of patients whose observed DOR reached at least the specified times of 6 or 12 months. Patients who did not have the opportunity to reach the specified timepoint were included in the denominator only	28 (93%)	31 (89%)	25 (96%)	84 (92%)
  Patients with observed DOR ≥12 months, n (%)	23 (77%)	24 (69%)	23 (88%)	70 (77%)

  Study 1423

  Among 26 CSCC patients in Study 1423, 16 had mCSCC and 10 had laCSCC. The median age was 73 years (52 to 88 years); 81% of patients were male; 92% of patients were White; the ECOG PS was 0 (38%) and 1 (62%); 58% of patients had received at least 1 prior anti-cancer systemic therapy; 92% of patients had received prior cancer-related surgery and 81% had received prior radiotherapy. One patient in the mCSCC group was dosed at 1 mg/kg. The rest received 3 mg/kg every 2 weeks.

  With a median duration of follow-up of 13.3 months, the confirmed ORR was 50% (95% CI: 30, 70); all responses were PRs. The median time to response was 1.9 months (range: 1.7 to 7.3 months) and 85% of responders had a DOR ≥6 months.

  Adjuvant treatment of CSCC at high risk of recurrence after surgery and radiation.

  The efficacy of LIBTAYO was evaluated in the C-POST study (NCT03969004), a randomized, double-blind, multicenter, placebo-controlled trial in 415 patients with CSCC at high risk of recurrence after surgery and radiation. Patients were required to complete adjuvant radiation therapy within 2 to 10 weeks of randomization. High risk of recurrence was defined as at least one of the following features:

  • Nodal Features:
    • Extracapsular extension (ECE) with ≥1 node ≥20 mm, or
    • ≥3 involved lymph nodes regardless of ECE
  • Non-Nodal Features:
    • In-transit metastases (skin or subcutaneous metastases > 2 cm from the primary lesion but not beyond the regional nodal basin),
    • Invasion of the skeleton or base of the skull (T4 Lesion),
    • Perineural Invasion, or
    • Locally recurrent tumor with ≥1 additional adverse feature listed below:
      • Multiple ipsilateral nodes
      • ≥T3 (≥4 cm diameter or bone erosion or invasion >6 mm)
      • Poorly differentiated histology and recurrent lesion ≥20 mm diameter

  The study excluded patients with autoimmune disease that required systemic therapy with immunosuppressant agents within 5 years; history of solid organ transplant; prior allogeneic or autologous stem cell transplantation; uncontrolled HIV, hepatitis B or hepatitis C infection, or ECOG PS ≥2.

  Patients were randomized 1:1 to receive LIBTAYO (N=209) or placebo (n=206). In the LIBTAYO arm, 171 patients received 350 mg LIBTAYO intravenously every 3 weeks for 12 weeks, followed by 700 mg LIBTAYO intravenously every 6 weeks for an additional 36 weeks, and 38 patients received 350 mg LIBTAYO intravenously every 3 weeks for up to 48 weeks. Treatment continued until disease recurrence, unacceptable toxicity, or up to 48 weeks.

  The major efficacy outcome measure was disease-free survival (DFS) defined as time from randomization to the first documented disease recurrence by investigator assessment or death due to any cause. Overall survival was an additional outcome measure.

  The median age was 71 years (range: 33 to 95); 84% were male; 91% were White, 3.1% were Asian, 5.4% were unknown or not reported, 0.5% were other; 9.4% were Hispanic or Latino, 83.4% were not Hispanic or Latino, 7% were unknown or not reported; 64% had ECOG PS of 0 and 36% had ECOG PS of 1. The location of tumor was head and neck (HN) in 83% of patients and non-HN in 17% of patients. The high-risk of recurrence feature was nodal in 58% of patients and non-nodal in 42% of patients.

  A statistically significant improvement in DFS was demonstrated in patients randomized to LIBTAYO compared with placebo. Improvement in DFS was similar in both dosage regimens. Efficacy results in C-POST study are summarized in Table 14 and Figure 1.

  Table 14: Efficacy Results for the C-POST Study in Patients with CSCC at High Risk of Recurrence in the Adjuvant Setting

  Efficacy Endpoints	LIBTAYO	Placebo
  	N = 209	N = 206
  CI: confidence interval; NE: not evaluable; NR: not reached
  Disease-Free Survival (DFS)
  Number of events, n (%)	24 (12%)	65 (32%)
  Disease recurrences, n (%) Distant recurrence, n (%) Locoregional recurrence, n (%)	18 (9%) 10 (4.8%) 8 (3.8%)	61 (30%) 26 (13%) 35 (17%)
  Deaths, n (%)	6 (2.9%)	4 (1.9%)
  Median (95% CI) in monthsBased on Kaplan-Meier method	NR (NE, NE)	49.4 (48.5, NE)
  Hazard ratio (95% CI)Based on stratified proportional hazards model	0.32 (0.20, 0.51)
  p-valueBased on a two-sided stratified log-rank test	<0.0001

  Figure 1: Kaplan-Meier Curve of DFS in the C-POST study

  

  Figure 1

  )

• for the treatment of adult patients with locally advanced or metastatic BCC (laBCC or mBCC) who have been previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. (
  1.2 Basal Cell Carcinoma

  LIBTAYO is indicated for the treatment of adult patients with locally advanced or metastatic basal cell carcinoma (laBCC or mBCC) who have been previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate.
  )

• in combination with platinum‐based chemotherapy for the first‐line treatment of adult patients with non-small cell lung cancer (NSCLC) with no EGFR, ALK or ROS1 aberrations and is:
  • locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or
  • metastatic. (
    1.3 Non-Small Cell Lung Cancer

    LIBTAYO in combination with platinum‐based chemotherapy is indicated for the first‐line treatment of adult patients with non-small cell lung cancer (NSCLC) with no EGFR, ALK or ROS1 aberrations and is:

    • locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or
    • metastatic.

    LIBTAYO as a single agent is indicated for the first-line treatment of adult patients with NSCLC whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥50%] as determined by an FDA-approved test

    [see Dosage and Administration (2.1)]

    , with no EGFR, ALK or ROS1 aberrations, and is:

    • locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or
    • metastatic.
    )
• as single agent for the first-line treatment of adult patients with NSCLC whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations, and is:
  • locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or
  • metastatic. (
    1.3 Non-Small Cell Lung Cancer

    LIBTAYO in combination with platinum‐based chemotherapy is indicated for the first‐line treatment of adult patients with non-small cell lung cancer (NSCLC) with no EGFR, ALK or ROS1 aberrations and is:

    • locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or
    • metastatic.

    LIBTAYO as a single agent is indicated for the first-line treatment of adult patients with NSCLC whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥50%] as determined by an FDA-approved test

    [see Dosage and Administration (2.1)]

    , with no EGFR, ALK or ROS1 aberrations, and is:

    • locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or
    • metastatic.
    ,
    2.1 Patient Selection for NSCLC

    Select patients with locally advanced or metastatic NSCLC for treatment with LIBTAYO as a single agent based on PD-L1 expression on tumor cells

    [see Clinical Studies (14.3)].

    Information on FDA-approved tests for the detection of PD-L1 expression is available at: http://www.fda.gov/CompanionDiagnostics.
    )

Administer LIBTAYO as an intravenous infusion over 30 minutes after dilution. (

• Metastatic and locally advanced CSCC and BCC: 350 mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months. (
  2.2 Recommended Dosage

  The recommended dosages of LIBTAYO are presented in Table 1.

  Refer to the Prescribing Information for the agents administered in combination with LIBTAYO for recommended dosing information, as appropriate.

  Table 1: Recommended Dosages of LIBTAYO as a Single Agent or in Combination with Other Agents

  Indication	Recommended dosage of LIBTAYO as an intravenous infusion	Duration of Treatment
  Adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC)	350 mg every 3 weeks	Until disease progression, unacceptable toxicity, or up to 24 months.
  Adjuvant treatment of adult patients with CSCC at high risk of recurrence after surgery and radiation	350 mg every 3 weeks for 12 weeks, followed by 700 mg every 6 weeks Or 350 mg every 3 weeks	Until disease recurrence, unacceptable toxicity, or up to 48 weeks.
  Adults with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC)	350 mg every 3 weeks	Until disease progression, unacceptable toxicity, or up to 24 months.
  Adults with non-small cell lung cancer (NSCLC)Single-agent or in combination with platinum-based chemotherapy	350 mg every 3 weeks	Until disease progression or unacceptable toxicity.
  )
• Adjuvant treatment of CSCC at high risk of recurrence after surgery and radiation:
  • 350 mg every 3 weeks for 12 weeks followed by 700 mg every 6 weeks until disease recurrence, unacceptable toxicity, or up to 48 weeks of total therapy, or
  • 350 mg every 3 weeks until disease recurrence, unacceptable toxicity, or up to 48 weeks of total therapy. (
    2.2 Recommended Dosage

    The recommended dosages of LIBTAYO are presented in Table 1.

    Refer to the Prescribing Information for the agents administered in combination with LIBTAYO for recommended dosing information, as appropriate.

    Table 1: Recommended Dosages of LIBTAYO as a Single Agent or in Combination with Other Agents

    Indication	Recommended dosage of LIBTAYO as an intravenous infusion	Duration of Treatment
    Adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC)	350 mg every 3 weeks	Until disease progression, unacceptable toxicity, or up to 24 months.
    Adjuvant treatment of adult patients with CSCC at high risk of recurrence after surgery and radiation	350 mg every 3 weeks for 12 weeks, followed by 700 mg every 6 weeks Or 350 mg every 3 weeks	Until disease recurrence, unacceptable toxicity, or up to 48 weeks.
    Adults with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC)	350 mg every 3 weeks	Until disease progression, unacceptable toxicity, or up to 24 months.
    Adults with non-small cell lung cancer (NSCLC)Single-agent or in combination with platinum-based chemotherapy	350 mg every 3 weeks	Until disease progression or unacceptable toxicity.
    )
• NSCLC: 350 mg every 3 weeks until disease progression or unacceptable toxicity. (
  2.2 Recommended Dosage

  The recommended dosages of LIBTAYO are presented in Table 1.

  Refer to the Prescribing Information for the agents administered in combination with LIBTAYO for recommended dosing information, as appropriate.

  Table 1: Recommended Dosages of LIBTAYO as a Single Agent or in Combination with Other Agents

  Indication	Recommended dosage of LIBTAYO as an intravenous infusion	Duration of Treatment
  Adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC)	350 mg every 3 weeks	Until disease progression, unacceptable toxicity, or up to 24 months.
  Adjuvant treatment of adult patients with CSCC at high risk of recurrence after surgery and radiation	350 mg every 3 weeks for 12 weeks, followed by 700 mg every 6 weeks Or 350 mg every 3 weeks	Until disease recurrence, unacceptable toxicity, or up to 48 weeks.
  Adults with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC)	350 mg every 3 weeks	Until disease progression, unacceptable toxicity, or up to 24 months.
  Adults with non-small cell lung cancer (NSCLC)Single-agent or in combination with platinum-based chemotherapy	350 mg every 3 weeks	Until disease progression or unacceptable toxicity.
  )

Injection: 350 mg/7 mL (50 mg/mL), clear to slightly opalescent, colorless to pale yellow solution that may contain trace amounts of translucent to white particles in a single-dose vial.

Lactation: Advise not to breastfeed. (