Aetna Commercial Clinical Policy

Aetna Tremelimumab-actl (Imjudo) Form

Effective Date

01/27/2023

Last Reviewed

08/23/2023

Original Document

  Reference



Background for this Policy

U.S. Food and Drug Administration (FDA)-Approved Indications

  • Imjudo is indicated in combination with durvalumab for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).
  • Imjudo is indicated in combination with durvalumab and platinum-based chemotherapy for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

    • Compendial Uses

    Recurrent and advanced NSCLC

    Tremelimumab-actl is available as Imjudo (AstraZeneca Pharmaceuticals LP) and is a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blocking human immunoglobulin G2 (IgG2) monoclonal antibody, Tremelimumab-actl is a negative regulator by functioning as a monoclonal antibody that binds to CTLA-4 which blocks the interaction with its ligands CD80 and CD86, releasing CTLA-4-mediated inhibition of T-cell activation. In synergistic mouse tumor models, blocking CTLA-4 activity showed decreased tumor growth and increased proliferation of T cells in tumors (AstraZeneca Pharmaceuticals, 2022).

    According to the prescribing information, tremelimumab-actl (Imjudo) carries the following warnings and precautions:

  • Immune-mediated adverse reactions, which may be severe or fatal and can include any of the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis with renal dysfunction and immune-mediated pancreatitis;
  • Infusion-related reactions;
  • Embryo-fetal toxicity.

    • Per the prescribing information the most common adverse reactions (≥ 20%) and most common laboratory abnormalities (≥ 40%) of patients with uHCC are as follows:

  • Adverse reactions: rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain;
  • Laboratory abnormalities: AST increased, ALT increased, hemoglobin decreased, sodium decreased, bilirubin increased, alkaline phosphatase increased, and lymphocytes decreased.

    • Per the prescribing information the most common adverse reactions (

    ≥ 20%) of patients with metastatic NSCLC are as follows: nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea.

    Refer to full prescribing information for Imjudo for use in specific populations.

    On October 21, 2022, the U.S. Food and Drug Administration (FDA) approved tremelimumab (Imjudo) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma (uHCC). The FDA approval was based on supporting data from the HIMALAYA study for efficacy assessment comparing 782 patients randomized to tremelimumab plus durvalumab (n=393) versus sorafenib (n=389) (AstraZeneca Pharmaceuticals, 2022; FDA, 2022b).

    The efficacy of tremelimumab in combination with durvalumab was evaluated in the HIMALAYA study, a randomized (1:1:1), open-label, multicenter study consisting of patients confirmed with unresectable hepatocellular carcinoma (uHCC) who had not received prior systemic treatment for HCC. Patient randomization was to one of three arms: tremelimumab 300 mg as a one-time single intravenous (IV) infusion plus durvalumab 1500 mg IV on the same day, followed by durvalumab 1500 mg IV every 4 weeks; durvalumab 1500 mg IV every 4 weeks; or sorafenib 400 mg orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall survival (OS). Additional outcome measures included: investigator-assessed progression-free survival (PFS), objective response rate (ORR) and duration of response (DoR) according to RECIST v1.1. The results demonstrated statistical significance and clinically meaningful improvement in OS in the tremelimumab plus durvalumab arm compared to the sorafenib arm (stratified hazard ratio [HR] of 0.78 [95% Confidence Interval (CI): 0.66, 0.92], 2-sided p value = 0.0035); median OS was 16.4 months (95% CI: 14.2, 19.6) versus 13.8 months (95% CI: 12.3,16.1). Median PFS was 3.8 months (95% CI: 3.7, 5.3) and 4.1 months (95% CI: 3.7, 5.5) for the tremelimumab plus durvalumab and sorafenib arms, respectively (stratified HR 0.90; 95% CI: 0.77, 1.05). ORR was 20.1% (95% CI:16.3, 24.4) in the tremelimumab plus durvalumab arm and 5.1% (95% CI: 3.2, 7.8) for those treated with sorafenib (AstraZeneca Pharmaceuticals, 2022; FDA, 2022b).

    On November 10, 2022, the U.S. Food and Drug Administration approved tremelimumab (Imjudo) in combination with durvalumab (Imfinzi) and platinum-based chemotherapy for adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. Efficacy was evaluated in the POSEIDON study, a randomized (1:1:1), multicenter, active-controlled, open-label study in patients with metastatic NSCLC who had not received prior systemic treatment. Patients were randomized to one of three treatment arms:

  • tremelimumab, durvalumab, and platinum-based chemotherapy for 4 cycles, followed by durvalumab and maintenance chemotherapy every 4 weeks. Patients were treated with a fifth tremelimumab dose at week 16;
  • durvalumab plus platinum-based chemotherapy for 4 cycles followed by durvalumab and maintenance chemotherapy; or
  • platinum-based chemotherapy for 6 cycles followed by maintenance chemotherapy.

    • Treatment was continued until disease progression or unacceptable toxicity. This approval was based on an efficacy comparison of treatment arm 1 (n=338) and 3 (n=337). The major efficacy endpoint measures were progression-free survival (PFS) and overall survival (OS). Tremelimumab plus durvalumab and platinum-based chemotherapy exhibited a statistically significant and clinically meaningful improvement in OS compared to platinum-based chemotherapy (hazard ratio [HR] of 0.77 [95% CI: 0.65, 0.92], 2-sided p-value = 0.00304); median OS was 14 months (95% CI: 11.7, 16.1) and 11.7 months (95% CI: 10.5, 13.1) in the treatment arm 1 and 3, respectively. Median PFS was 6.2 months (95% CI: 5.0, 6.5) and 4.8 months (95% CI 4.6, 5.8) in the treatment arms, respectively (HR 0.72 [95% CI: 0.60, 0.86], 2-sided p-value = 0.00031). Overall response rate was 39% (95% CI: 34, 44) in and 24% (95% CI: 20, 29) in the treatment arm 1 and 3, respectively. Median duration of response was 9.5 months (95% CI: 7.2, not reached) and 5.1 months (95% CI: 4.4, 6.0) in the two treatment arms (AstraZeneca Pharmaceuticals, 2022; FDA, 2022a).

    Note

    : Requires Precertification:

    Precertification of tremelimumab-actl (Imjudo) is required of all Aetna participating providers and members in applicable plan designs. For precertification of tremelimumab-actl (Imjudo),

    call (866) 752-7021 (commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification . For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

    Criteria for Initial Approval

    Hepatocellular Carcinoma

    Aetna considers tremelimumab-actl (Imjudo) medically necessary for a one-time single dose treatment of unresectable hepatocellular carcinoma in combination with durvalumab (Imfinzi).

    Non-small Cell Lung Cancer (NSCLC)

    Aetna considers tremelimumab-actl (Imjudo) medically necessary for a total of 5 doses for treatment of recurrent, advanced, or metastatic non-small cell lung cancer (NSCLC) when

    all

    of the following criteria are met:

  • The requested medication will be used in combination with durvalumab (Imfinzi) and platinum-based chemotherapy;
    • and
  • The tumor is negative for EGFR exon 19 deletion and L858R mutations and ALK gene mutations.

    • Aetna considers all other indications as experimental and investigational.

    Continuation of Therapy

    See Dosage and Administration information.

    Dosage and Administration

    Tremelimumab-actl is supplied as Imjudo 25 mg/1.25 mL (20 mg/mL) and 300 mg/15 mL (20 mg/mL) solution in a single-dose vial injection for intravenous use.

    The recommended Imjudo dosage is administered as an intravenous infusion over 60 minutes after dilution and is as follows:

    Unresectable Hepatocellular Carcinoma (uHCC)

    Imjudo is administered as an intravenous infusion over 60 minutes after dilution with the recommended dosage as follows:

  • For persons with a body weight 30 kg and more: Administer Imjudo 300 mg as a single dose in combination with durvalumab 1,500 mg at cycle 1/day1, followed by durvalumab as a single agent every 4 weeks.
  • For persons with a body weight less than 30 kg: Administer Imjudo 4 mg/kg as a single dose in combination with durvalumab 20 mg/kg at cycle 1/day 1, followed by durvalumab as a single agent every 4 weeks.

    • Metastatic Non-small Cell Lung Cancer (NSCLC)

  • For persons with a body weight of 30 kg and more: Administer Imjudo 75 mg every 3 weeks in combination with durvalumab 1,500 mg and platinum-based chemotherapy for 4 cycles, and then administer durvalumab 1,500 mg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of Imjudo 75 mg in combination with durvalumab dose 6 at week 16.
  • For persons with a body weight less than 30 kg: Administer Imjudo 1 mg/kg every 3 weeks in combination with durvalumab 20 mg/kg and platinum-based chemotherapy for 4 cycles, and then administer durvalumab 20 mg/kg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of Imjudo 1 mg/kg in combination with durvalumab dose 6 at week 16.

    • Refer to full prescribing information for Imjudo for preparation and administration instructions and dosage modifications for adverse reactions.

    Source:

    AstraZeneca Pharmaceuticals, 2022