| Coverage Policy Manual | |
| Policy #: | 2023010 |
| Category: | Pharmacy |
| Initiated: | March 2023 |
| Last Review: | April 2024 |
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| Tremelimumab-actl (e.g., Imjudo) | |
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| Description: |
Tremelimumab-actl (e.g., Imjudo®) is a monoclonal antibody that binds to CTLA-4 and blocks the interaction with its ligands CD80 and CD86, releasing CTLA-4-mediated inhibition of T-cell activation. Blocking CTLA-4 activity resulted in decreased tumor growth and increased proliferation of T cells in tumors. (FDA, 2022)
Regulatory Status
Tremelimumab-actl (e.g., Imjudo®)was approved by the U.S. Food and Drug Administration (FDA) on October 24, 2022 in combination with durvalumab for the treatment of adult individuals with unresectable hepatocellular carcinoma (uHCC) and 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.
Coding
See CPT/HCPCS section below.
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Policy/ Coverage: |
For members of plans that utilize an oncology benefits management program, prior approval is required for this service when rendered for oncologic indications and is managed through the oncology benefits management program.
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Tremelimumab-actl (e.g., Imjudo®) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
Hepatocellular Carcinoma (HCC) APPROVAL for a single dose:
Non-Small Cell Lung Cancer (NSCLC) APPROVAL for 12 months:
Esophageal and Esophagogastric Junction Cancers
*Consider neoadjuvant immunotherapy in combination with durvalumab as primary treatment for adenocarcinoma if tumor is microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) and patient is medically fit for surgery with cT2, N0 (high-risk lesions: lymphovascular invasion, ≥ 3cm, poorly differentiated), cT1b-cT2, N+ or cT3-cT4a, Any N disease (useful in certain circumstances) (NCCN 2A)
Gastric Cancer
*Consider neoadjuvant immunotherapy in combination with durvalumab as primary treatment if tumor is microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors for potentially resectable locoregional disease (cT2 or higher, any N) if medically fit for surgery (useful in certain circumstances) (NCCN 2A)
*NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
Policy Guidelines
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
0 = Fully active, able to continue all pre-disease performance without restriction
1 = Restricted in physically strenuous activity but ambulatory and able to conduct work of a light or sedentary nature, for example, light housework, office work
2 = Ambulatory and capable of all self-care but unable to conduct any work activities. Up and about more than 50% of waking hours
3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5 = Dead
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
Dosage and Administration
Dosing per FDA Guidelines
The recommended dose of Tremelimumab-actl (e.g., Imjudo®) is based on indication and weight.
1. HCC:
a. Weight 30 kg and more:
Tremelimumab-actl 300 mg as a single dose in combination with durvalumab 1,500 mg at Cycle 1/Day 1, followed by durvalumab as a single agent every 4 weeks
b. Weight less than 30 kg:
Tremelimumab-actl 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.
2. NSCLC:
a. Weight 30 kg and more:
Tremelimumab-actl 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 Tremelimumab-actl 75 mg in combination with durvalumab dose 6 at week 16.
b. Weight less than 30 kg:
Tremelimumab-actl 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 Tremelimumab-actl 1 mg/kg in combination with durvalumab dose 6 at week 16.
3. Esophageal and Esophagogastric Junction Canc1ers (V 1.2024, NCCN 2A)
For neoadjuvant therapy only
Tremelimumab-actl 300 mg as a single dose, Day 1, in combination with durvalumab 1,500 mg on Day 1, 29 and 57 for 12 weeks preoperatively for 1 cycle only. (NCCN Guideline 1.2024)
4. Gastric Cancers (V 1.2024, NCCN 2A)
For neoadjuvant therapy only
Tremelimumab-actl 300 mg as a single dose, Day 1, in combination with durvalumab 1,500 mg on Day 1, 29 and 57 for 12 weeks preoperatively for 1 cycle only. (NCCN Guideline 1.2024)
Tremelimumab-actl is available as 25mg/1.25mL (20mg/mL) and 300 mg/15 mL (20 mg/mL) solution in a single dose vial.
Tremelimumab-actl should be administered as an intravenous infusion by a healthcare professional.
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Tremelimumab-actl (e.g., Imjudo®), for any indication or circumstance not described above, including but not limited to the circumstances listed below, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, Tremelimumab-actl (e.g., Imjudo®), for any indication or circumstance not described above, including but not limited to the circumstances listed below, is considered investigational.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective September 2023 - March 2024
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Tremelimumab-actl (e.g., Imjudo®) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
Hepatocellular Carcinoma (HCC) APPROVAL for a single dose:
1. Individual is 18 years of age or older (Imjudo, 2022); AND
2. Individual is diagnosed with locally advanced unresectable and/or metastatic hepatocellular carcinoma (Imjudo, 2022) (NCCN, 1); AND
3. Individual has no history of prior system treatment, including treatment with programmed cell death protein 1 (PD-1) or programmed death ligand-1 (PD-L1) inhibitors (Imjudo, 2022) (NCCN 1); AND
4. Individual will be using in combination with durvalumab (Imjudo, 2022) (NCCN 1); AND
5. Individual is using as a one-time treatment (Imjudo, 2022); AND
6. Must be dosed in accordance with the FDA label.
Non-Small Cell Lung Cancer (NSCLC) APPROVAL for 12 months:
1. Individual is 18 years of age or older (Imjudo, 2022); AND
2. Individual is diagnosed with recurrent, advanced, or metastatic NSCLC (Imjudo, 2022) (NCCN 1); AND
3. Individual has no history of prior system treatment, including treatment with PD-1 or PD-L1 inhibitors (Imjudo, 2022); AND
4. Individual will be using in combination with durvalumab and one of the following (Imjudo, 2022) (NCCN 1):
5. Individual has an ECOG performance status of 0-2 (NCCN 2A); AND
6. Must be dosed in accordance with the FDA label.
Esophageal and Esophagogastric Junction Cancers
*Consider neoadjuvant immunotherapy in combination with durvalumab as primary treatment for adenocarcinoma if tumor is microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) and patient is medically fit for surgery with cT2, N0 (high-risk lesions: lymphovascular invasion, ≥ 3cm, poorly differentiated), cT1b-cT2, N+ or cT3-cT4a, Any N disease (useful in certain circumstances) (NCCN 2A)
Gastric Cancer
*Consider neoadjuvant immunotherapy in combination with durvalumab as primary treatment if tumor is microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors for potentially resectable locoregional disease (cT2 or higher, any N) if medically fit for surgery (useful in certain circumstances) (NCCN 2A)
*NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
0 = Fully active, able to carry on all pre-disease performance without restriction
1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light housework, office work
2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5 = Dead
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
Dosage and Administration
Dosing per FDA Guidelines
The recommended dose of Tremelimumab-actl based on indication and weight.
1. HCC:
a. Weight 30 kg and more: Tremelimumab-actl 300 mg as a single dose in combination with durvalumab 1,500 mg at Cycle 1/Day 1, followed by durvalumab as a single agent every 4 weeks
b. Weight less than 30 kg: Tremelimumab-actl 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.
2. NSCLC:
a. Weight 30 kg and more: Tremelimumab-actl 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 Tremelimumab-actl 75 mg in combination with durvalumab dose 6 at week 16
b. Weight less than 30 kg: Tremelimumab-actl 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 Tremelimumab-actl 1 mg/kg in combination with durvalumab dose 6 at week 16.
3. Esophageal and Esophagogastric Junction Cancers (V 3.2023, NCCN 2A)
For neoadjuvant therapy only
Tremelimumab-actl 300 mg as a single dose, Day 1, in combination with durvalumab 1,500 mg on Day 1, 29 and 57 for 12 weeks preoperatively for 1 cycle only. (NCCN Guideline 3.2023)
4. Gastric Cancers (V 2.2023, NCCN 2A)
For neoadjuvant therapy only
Tremelimumab-actl 300 mg as a single dose, Day 1, in combination with durvalumab 1,500 mg on Day 1, 29 and 57 for 12 weeks preoperatively for 1 cycle only. (NCCN Guideline 2.2023)
Tremelimumab-actl is available as 25mg/1.25mL (20mg/mL) and 300 mg/15 mL (20 mg/mL) solution in a single dose vial.
Tremelimumab-actl should be administered as an intravenous infusion by a healthcare professional.
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Tremelimumab-actl, for any indication or circumstance not described above, including but not limited to the circumstances listed below, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
1. Individuals with active co-infection of viral hepatitis B and/or hepatitis C (Imjudo, 2022)
For members with contracts without primary coverage criteria, tremelimumab-actl, for any indication or circumstance not described above, including but not limited to the circumstances listed below, is considered investigational.
1. Individuals with active co-infection of viral hepatitis B and/or hepatitis C (Imjudo, 2022)
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Prior Approval is required for Tremelimumab-actl (e.g., Imjudo).
For members of plans that utilize an oncology benefits management program, prior approval is required for this service when rendered for oncologic indications and is managed through the oncology benefits management program.
Effective March 29, 2023
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Tremelimumab-actl meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
Hepatocellular Carcinoma (HCC)
APPROVAL for a single dose:
Non-Small Cell Lung Cancer (NSCLC)
APPROVAL for 12 months:
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
Dosage and Administration
Dosing per FDA Guidelines
The recommended dose of Tremelimumab-actl based on indication and weight.
Tremelimumab-actl is available as 25mg/1.25mL (20mg/mL) and 300 mg/15 mL (20 mg/mL) solution in a single dose vial.
Tremelimumab-actl should be administered as an intravenous infusion by a healthcare professional.
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Tremelimumab-actl, for any indication or circumstance not described above, including but not limited to the circumstances listed below, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, tremelimumab-actl, for any indication or circumstance not described above, including but not limited to the circumstances listed below, is considered investigational.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
The efficacy of tremelimumab-actl in combination with durvalumab was evaluated in a randomized (1:1:1), open-label, multicenter study in patients with confirmed uHCC who had not received prior systemic treatment for HCC. Patients were randomized to one of two investigational arms (tremelimumab-actl plus durvalumab or durvalumab) or sorafenib. Study treatment consisted of tremelimumab-actl as a one-time single intravenous infusion of 300 mg in combination with durvalumab 1,500mg on the same day, followed by durvalumab every 4 weeks; durvalumab 1,500 mg every 4 weeks (an unapproved regimen for uHCC); or sorafenib 400 mg given orally twice daily, until disease progression or unacceptable toxicity.
The efficacy assessment of tremelimumab-actl is based on patients randomized to the tremelimumab-actl plus durvalumab arm versus the sorafenib arm. Randomization was stratified by macrovascular invasion (MVI) (yes or no), etiology of liver disease (hepatitis B virus vs. hepatitis C virus vs. others) and ECOG performance status (0 vs. 1).
The study enrolled patients with BCLC Stage C or B (not eligible for locoregional therapy). The study
excluded patients with co-infection of viral hepatitis B and hepatitis C; active or prior documented gastrointestinal (GI) bleeding within 12 months; ascites requiring non-pharmacologic intervention within 6 months; hepatic encephalopathy within 12 months before the start of treatment; active or prior documented autoimmune or inflammatory disorders. Esophagogastroduodenoscopy was not mandated prior to enrollment but adequate endoscopic therapy, according to institutional standards, was required for patients with a history of esophageal variceal bleeding or those assessed as high risk for esophageal variceal bleeding by the treating physician. Study treatment was permitted beyond disease progression if the patient was clinically stable and was deriving clinical benefit as determined by the investigator.
The major efficacy outcome measure was overall survival (OS) between the tremelimumab-actl plus durvalumab arm versus the sorafenib arm. Additional efficacy outcomes were investigator-assessed progression-free survival (PFS), objective response rate (ORR) and duration of response (DoR) according to RECIST v1.1. Tumor assessments were conducted every 8 weeks for the first 12 months and then every 12 weeks thereafter.
The overall survival rate in the tremelimumab-actl plus durvalumab arm versus the sorafenib arm was 33.3% vs 24.7%, respectively. The median overall survival in months was 16.4 months in the tremelimumab-actl plus durvalumab arm versus 13.8 months in the sorafenib arm. (Imjudo, 2022)
The efficacy of tremelimumab-actl in combination with durvalumab and platinum-based chemotherapy in previously untreated metastatic NSCLC patients with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations was investigated in POSEIDON, a randomized, multicenter, active-controlled, open-label trial. Eligible patients had Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 and must have had no prior chemotherapy or any other systemic therapy for metastatic NSCLC. Choice of platinum-based chemotherapy was at the Investigator’s discretion, taking into consideration the calculated creatinine clearance. Patients with active and/or untreated brain metastases; a history of active primary immunodeficiency; autoimmune disorders including active or prior documented autoimmune or inflammatory disorders; use of systemic immunosuppressants within 14 days before the first dose of the treatment except physiological dose of systemic corticosteroids were ineligible. Randomization was stratified by tumor cells (TC) PD-L1 expression (TC ≥ 50% vs. TC < 50%), disease stage (Stage IVA vs. Stage IVB), and histology (non-squamous vs. squamous).
Patients were randomized 1:1:1 to receive tremelimumab-actl in combination with durvalumab and platinum-based chemotherapy according to the regimens listed below, durvalumab and platinum-based chemotherapy (an unapproved regimen for metastatic NSCLC), or platinum-based chemotherapy.
The evaluation of efficacy for metastatic NSCLC relied on comparison between:
Tremelimumab-actl was given up to a maximum of 5 doses. Durvalumab and histology-based pemetrexed continued every 4 weeks until disease progression or unacceptable toxicity. Administration of durvalumab monotherapy was permitted beyond disease progression if the patient was clinically stable and deriving clinical benefit as determined by the Investigator. Patients with disease progression during durvalumab monotherapy were given the option to be retreated with 4 additional cycles of tremelimumab-actl in combination with durvalumab. Tumor assessments were performed at Week 6, Week 12, and then every 8 weeks thereafter.
The major efficacy outcome measures were progression free survival (PFS) and overall survival (OS) of tremelimumab-actl and durvalumab in combination with platinum-based chemotherapy compared to platinum-based chemotherapy alone. Additional efficacy outcome measures were overall response rate (ORR) and duration of response (DoR). PFS, ORR, and DoR were assessed using Blinded Independent Central Review (BICR) according to RECIST v1.1. A total of 675 patients were randomized to receive either tremelimumab-actl with durvalumab and platinum-based chemotherapy (n=338) or platinum-based chemotherapy (n=337).
Progression free survival was significantly improved with durvalumab plus chemotherapy versus chemotherapy alone (6.2 months vs 4.8 months, respectively). The overall survival rate in the tremelimumab-actl with durvalumab plus chemotherapy arm versus chemotherapy alone arm was 26% vs 15%, respectively. The median overall survival in months was 14.0 months in the tremelimumab-actl with durvalumab and platinum-based chemotherapy arm versus 11.7 months in the platinum-based chemotherapy arm. (Imjudo, 2022)
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2024. No new literature was identified that would prompt a change in the coverage statement.
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| CPT/HCPCS: | |
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| References: |
Imjudo [package insert]. Wilmington, DE. AstraZeneca Pharmaceuticals; Accessed at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761270s000lbl.pdf Johnson, Melissa L., et al.(2023) “Durvalumab with or without Tremelimumab in Combination with Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III Poseidon Study.” Journal of Clinical Oncology, vol. 41, no. 6, 2023, pp. 1213–1227., https://doi.org/10.1200/jco.22.00975. Accessed March 17, 2023. National Comprehensive Cancer Network (NCCN)(2023) National Comprehensive Cancer Network, Inc. 2023. Hepatocellular Carcinoma 1.2023. National Comprehensive Cancer Network, Inc. 2023. Hepatocellular Carcinoma 1.2023. National Comprehensive Cancer Network (NCCN)(2023) National Comprehensive Cancer Network, Inc. 2023. Non-Small Cell Lung Cancer 2.2023. Accessed March 21, 2023. |
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Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2025 American Medical Association. |
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