Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual
Policy #:	2024015
Category:	Pharmacy
Initiated:	May 2024
Last Review:	June 2025

Toripalimab-tpzi (e.g., Loqtorzi)

Description:

Toripalimab is a humanized IgG4 monoclonal antibody that binds to the programmed death receptor-1 (PD-1) found on T-cells and blocks its interaction with PD-ligand 1 (PD-L1) and PD-L2. Immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic adverse reactions, and solid organ transplant rejection have been reported with toripalimab in clinical trials; treatment with high-dose corticosteroids may be necessary for individuals who develop immune-mediated toxicity.

Regulatory Status

Toripalimab-tpzi (e.g., Loqtorzi) was approved by the U.S. Food and Drug Administration (FDA) on October 27, 2023, for the treatment of nasopharyngeal carcinoma (NPC) in the following situations:

1) In combination with cisplatin and gemcitabine for first-line treatment of adults with metastatic or with recurrent locally advanced disease; 2) As a single agent for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy.

Coding

See CPT/HCPCS Code section below.

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.

Approval timeframes may differ for members/participants of Self-Insured plans.

Effective June 18, 2025

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Toripalimab-tpzi (e.g., Loqtorzi) 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:

For FDA labeled indications, Toripalimab-tpzi (e.g., Loqtorzi) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.

For off-label indications, authorizations will not exceed the maximum FDA labeled dose and frequency across all the FDA labeled indications unless higher dose is allowed for the specific indication in the dosage and administration section.

FDA Labeled Indications:

INITIAL APPROVAL STANDARD REVIEW to 12 months:

1. Individual is 18 years of age or older; AND

2. Individual has a diagnosis of cancer of the nasopharynx with ANY of the following:

a. Toripalimab will be used as a first-line systemic therapy in combination with cisplatin and gemcitabine for tumor stage 1-4, lymph node involvement stage 0-3 with evidence of distant metastasis in:

i. Oligometastatic disease and ECOG performance status 0-2 (NCCN 1); OR

ii. Widely metastatic disease and ECOG performance status 0-2 (NCCN 1); OR

b. If not previously used, toripalimab will be used as subsequent-line systemic therapy in combination with cisplatin and gemcitabine for tumor stage 1-4, lymph node involvement stage 0-3 with evidence of distant metastasis in:

i. Oligometastatic disease and ECOG performance status 0-2 (NCCN 2A); OR

ii. Widely metastatic disease and ECOG performance status 0-2 (NCCN 2A); OR

c. Toripalimab will be used as a subsequent-line single agent systemic therapy if disease has progressed on or after platinum-containing therapy for tumor stage 1-4, lymph node involvement stage 0-3 with evidence of distant metastasis in:

i. Oligometastatic disease and ECOG performance status 0-2 (NCCN 2A); OR

ii. Widely metastatic disease and ECOG performance status 0-2 (NCCN 2A); OR

3. Individual has a diagnosis of a very advanced head and neck cancer with ANY of the following:

a. Toripalimab will be used in systemic therapy as a first line (NCCN 1) or subsequent line (NCCN 2A, if not previously used) option in individuals with nasopharyngeal cancer and an ECOG performance status of 0-1 for:

i. Unresectable locoregional recurrence with prior radiation therapy; OR

ii. Unresectable second primary disease with prior radiation therapy; OR

iii. Recurrent/persistent disease with distant metastases in combination with cisplatin and gemcitabine; OR

b. Toripalimab will be used in systemic therapy as an alternate single agent subsequent line option in disease progression on or after platinum-containing therapy for nasopharyngeal cancer and an ECOG performance status of 0-3 for:

i. Unresectable locoregional recurrence with prior radiation therapy (NCCN 2A); OR

ii. Unresectable second primary disease with prior radiation therapy (NCCN 2A); OR

iii. Unresectable persistent disease with prior radiation therapy (NCCN 2A); OR

iv. Recurrent/persistent disease with distant metastases (NCCN 2A);

CONTINUED APPROVAL for 12 months:

1. Individual continues to meet the initial approval criteria; AND

2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND

3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, complications of allogeneic hematopoietic stem cell transplantation, solid organ transplant rejection); AND

4. When used as a first line therapy, individual has not exceeded a maximum of 24 months of therapy;

Off Label Indications:

The use of this drug for off-label indications not listed below is subject to policy 200030.

INITIAL APPROVAL STANDARD REVIEW for 12 months:

The following indications are covered when the individual meets the related NCCN category 1

or 2A recommendations specific to the indications below (e.g., histology, cancer staging,

surgical status, mono- or combination therapy, and previous lines of therapy):

1. COLON CANCER (NCCN 2A); OR

Appendiceal Cancer (NCCN 2A); OR

2. Head and Neck Cancers (NCCN 2A); OR

Cancers of the Nasopharynx (NCCN 1 and 2A); OR

Very Advanced Head and Neck Cancer (NCCN 1 and 2A);

3. SMALL BOWEL CANCER (NCCN 2A); OR

4. ANAL CANCER (NCCN 2A); OR

5. RECTAL CELL LUNG CANCER (NCCN 2A)

CONTINUED APPROVAL for 12 months:

1. Individual continues to meet the initial approval criteria; AND

2. Documentation indicating disease response to treatment, by stabilization of disease and decrease in size of tumor or tumor spread; AND

3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, complications of allogeneic hematopoietic stem cell transplantation, solid organ transplant rejection);

Please see the NCCN Drugs and Biologics Compendium for a complete list of NCCN 1 & 2A

indications. To view the most recent and complete version of the guideline or Compendium,

go online to NCCN.org. Please note, 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 TNM Classification is a system for classifying a malignancy. The system has its basis on assessing the tumor, regional lymph nodes, and distant metastasis, as detailed below.

T - Tumor. Used to describe the size of the primary tumor and its' invasion into adjacent tissues. T0 indicates that no evidence of tumor is present, while T1-T4 are used to identify the size and extension of the tumor, with progressive enlargement and invasiveness from T1 to T4.

N - Nodes. Used to describe regional lymph node involvement of the tumor. N0 indicates no regional nodal spread, while N1-N3 indicates some degree of nodal spread, with a progressively distal spread from N1 to N3.

M - Metastasis. Used to identify the presence of distant metastases of the primary tumor. A tumor is classified as M0 if no distant metastasis is present and M1 if there is evidence of distant metastasis (Rosen, 2023).

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

Dosage and Administration

Dosing per FDA Guidelines unless otherwise specified below.

The recommended dose of toripalimab is 240 mg intravenously every three weeks when used in combination with cisplatin and gemcitabine, and 3 mg/kg intravenously every two weeks when used as a single agent.

Toripalimab is available as a 240 mg/6mL solution in a single-dose vial.

Toripalimab 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

Toripalimab-tpzi (e.g., Loqtorzi) for any indication or circumstance not described above, 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, toripalimab-tpzi (e.g., Loqtorzi), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective May 29, 2024- June 17, 2025

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Toripalimab 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:

For FDA labeled indications, all products must be dosed in accordance with the FDA label unless otherwise specified.

For off-label indications, authorizations will not exceed 480 mg every 2 weeks OR maximum recommended doses as outlined in dosage and administration section.

INITIAL APPROVAL STANDARD REVIEW for up to 6 months:

1. Individual is 18 years of age or older; AND

2. Individual has a diagnosis of cancer of the nasopharynx with ANY of the following:

a. Toripalimab will be used as a first-line systemic therapy in combination with cisplatin and gemcitabine for tumor stage 1-4, lymph node involvement stage 0-3 with evidence of distant metastasis in:

i. Oligometastatic disease and ECOG performance status 0-2 (NCCN 1); OR

ii. Widely metastatic disease and ECOG performance status 0-2 (NCCN 1); OR

b. If not previously used, toripalimab will be used as subsequent-line systemic therapy in combination with cisplatin and gemcitabine for tumor stage 1-4, lymph node involvement stage 0-3 with evidence of distant metastasis in:

i. Oligometastatic disease and ECOG performance status 0-2 (NCCN 2A); OR

ii. Widely metastatic disease and ECOG performance status 0-2 (NCCN 2A); OR

c. Toripalimab will be used as a subsequent-line single agent systemic therapy if disease has progressed on or after platinum-containing therapy for tumor stage 1-4, lymph node involvement stage 0-3 with evidence of distant metastasis in:

i. Oligometastatic disease and ECOG performance status 0-2 (NCCN 2A); OR

ii. Widely metastatic disease and ECOG performance status 0-2 (NCCN 2A); OR

3. Individual has a diagnosis of a very advanced head and neck cancer with ANY of the following:

a. Toripalimab will be used in systemic therapy as a first line (NCCN 1) or subsequent line (NCCN 2A, if not previously used) option in individuals with nasopharyngeal cancer and an ECOG performance status of 0-1 for:

i. Unresectable locoregional recurrence with prior radiation therapy; OR

ii. Unresectable second primary disease with prior radiation therapy; OR

iii. Recurrent/persistent disease with distant metastases in combination with cisplatin and gemcitabine; OR

b. Toripalimab will be used in systemic therapy as an alternate single agent subsequent line option in disease progression on or after platinum-containing therapy for nasopharyngeal cancer and an ECOG performance status of 0-3 for:

i. Unresectable locoregional recurrence with prior radiation therapy (NCCN 2A); OR

ii. Unresectable second primary disease with prior radiation therapy (NCCN 2A); OR

iii. Unresectable persistent disease with prior radiation therapy (NCCN 2A); OR

iv. Recurrent/persistent disease with distant metastases (NCCN 2A); AND

4. Must be dosed in accordance with the FDA label unless otherwise specified.

CONTINUED APPROVAL for up to 12 months:

1. Individual continues to meet the initial approval criteria; AND

2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND

3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, complications of allogeneic hematopoietic stem cell transplantation, solid organ transplant rejection); AND

4. When used as a first line therapy, individual has not exceeded a maximum of 24 months of therapy; AND

5. Must be dosed in accordance with the FDA label unless otherwise specified.

Off-label

The use of this drug is covered if an FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all 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).

Policy Guidelines

The TNM Classification is a system for classifying a malignancy. The system has its basis on assessing the tumor, regional lymph nodes, and distant metastasis, as detailed below.

T - Tumor. Used to describe the size of the primary tumor and its' invasion into adjacent tissues. T0 indicates that no evidence of tumor is present, while T1-T4 are used to identify the size and extension of the tumor, with progressive enlargement and invasiveness from T1 to T4.

N - Nodes. Used to describe regional lymph node involvement of the tumor. N0 indicates no regional nodal spread, while N1-N3 indicates some degree of nodal spread, with a progressively distal spread from N1 to N3.

M - Metastasis. Used to identify the presence of distant metastases of the primary tumor. A tumor is classified as M0 if no distant metastasis is present and M1 if there is evidence of distant metastasis (Rosen, 2023).

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

Dosage and Administration

Dosing per FDA Guidelines where applicable. For off-label indications, authorizations will not exceed 480 mg every two weeks OR maximum recommended doses as outlined below.

Toripalimab is available as a 240 mg/6mL solution in a single-dose vial.

Toripalimab 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

Toripalimab for any indication or circumstance not described above, 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, toripalimab, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:

The efficacy of toripalimab in combination with cisplatin and gemcitabine was investigated in JUPITER-02 (NCT03581786), a randomized, multicenter, single region, double-blind, placebo-controlled trial in 289 patients with metastatic or recurrent, locally advanced NPC who had not received previous systemic chemotherapy for recurrent or metastatic disease. Patients with recurrent NPC after treatment with curative intent were required to have an interval of at least 6 months between the last dose of radiotherapy or chemotherapy and recurrence. Patients with autoimmune disease, other than stable hypothyroidism or Type I diabetes, and patients who required systemic immunosuppression were ineligible. Randomization was stratified according to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (0 versus 1) and disease stage (recurrent versus metastatic). Patients were randomized (1:1) to receive one of the following treatments: 1) Toripalimab 240 mg intravenously every 3 weeks in combination with cisplatin 80 mg/m2 on Day 1 every 3 weeks gemcitabine 1000 mg/m2 on Days 1 and 8 for up to 6 cycles, followed by toripalimab 240 mg once every 3 weeks, or 2) Placebo intravenously every 3 weeks in combination with cisplatin 80 mg/m2 on Day 1 every 3 weeks and gemcitabine 1000 mg/m2 on Days 1 and 8 for up to 6 cycles, followed by placebo once every 3 weeks. Treatment with toripalimab or placebo continued until disease progression per RECIST v1.1, unacceptable toxicity, or a maximum of 2 years. Tumor assessments were performed every 6 weeks for the first 12 months and every 9 weeks thereafter. The main efficacy outcome measure was Blinded Independent Review Committee (BIRC)-assessed progression-free survival (PFS) according to RECIST v1.1. Additional efficacy outcome measures include BIRC-assessed overall response rate (ORR) and overall survival (OS).

The trial demonstrated statistically significant improvements in BIRC-assessed PFS, ORR and OS for patients randomized to toripalimab in combination with cisplatin/gemcitabine compared to cisplatin and gemcitabine with placebo.

The efficacy of toripalimab was investigated in POLARIS-02 (NCT 02915432), an open-label, multicenter, multicohort trial conducted in a single country. The trial included a total of 172 patients with unresectable or metastatic NPC who had received prior platinum-based chemotherapy for treatment of recurrent or metastatic NPC or had disease progression within 6 months of completion of platinum-based chemotherapy administered as neoadjuvant, adjuvant, or definitive chemoradiation treatment for locally advanced disease. Key exclusion criteria included previous treatment with an anti-PD-(L)1 antibody; active autoimmune disease or other medical conditions requiring immunosuppressive therapy. Patients received toripalimab 3 mg/kg intravenously every 2 weeks until disease progression per RECIST v1.1 or unacceptable toxicity. Tumor response assessments were performed every 8 weeks for the first year and every 12 weeks thereafter. The major efficacy outcome measures were confirmed ORR and duration of response (DOR) as assessed by a Blinded Independent Review Committee (BIRC) using RECIST v1.1. The median age was 45 years (range: 22 to 68), 4.1% age 65 or older, 83% male, 100% Asian, and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 (37%). Patients had received a median of 2 prior systemic therapies for recurrent/metastatic disease (range: 1-13). Ninety-five percent of patients had metastatic disease, 95% had non-keratinizing NPC, 2.9% had keratinizing squamous cell carcinoma and 1.7% did not have the subtype identified. The trial demonstrated statistically significant improvements in BIRC-assessed PFS, ORR and OS for patients randomized to toripalimab.

2025 Update

Annual policy review completed with a literature search using the MEDLINE database through June 2025.

CPT/HCPCS:

References:

Loqtorzi(2023) package insert Redwood City, CA: Coherus Biosciences; 2023.

Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J.(2021) Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nature medicine. 2021 Sep;27(9):1536-43.

NCCN(2024) Drugs & Biologics Compendium for Toripalimab-tpzi, (Loqtorzi) National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed on 28 March 2024. To view the most recent and complete version of the Compendium, go online to NCCN.org.

Rosen RD, Sapra A.(2023) TNM Classification. Updated 2023 Feb 13. StatPearls (Internet). Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553187/

Wang ZX, Cui C, Yao J, Zhang Y, Li M, Feng J, Yang S, Fan Y, Shi J, Zhang X, Shen L.(2022) Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial. Cancer cell. 2022 Mar 14;40(3):277-88.

Zhang L, Hao B, Geng Z, Geng Q.(2022) Toripalimab: the first domestic anti-tumor PD-1 antibody in China. Frontiers in immunology. 2022 Jan 12;12:730666.

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.