Toripalimab-tpzi (Loqtorzi)

Number: 1049

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses toripalimab-tpzi (Loqtorzi) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of toripalimab-tpzi (Loqtorzi) is required of all Aetna participating providers and members in applicable plan designs. For precertification of toripalimab-tpzi (Loqtorzi), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

Note: Site of Care Utilization Management Policy applies. For information on site of service for Toripalimab-tpzi (Loqtorzi), see Utilization Management Policy on Site of Care for Specialty Drug Infusions. 

1. Exclusions 

   Aetna considers members not eligible for Loqtorzi when they have experienced disease progression while on PD-1 or PD-L1 inhibitor therapy.

2. Criteria for Initial Approval

   1. Anal Carcinoma

      Aetna considers toripalimab-tpzi (Loqtorzi) medically necessary as a single agent for subsequent treatment of metastatic anal carcinoma if the member has not received prior immunotherapy.

   2. Colorectal Cancer

      Aetna considers toripalimab-tpzi (Loqtorzi) medically necessary as a single agent for the treatment of unresectable, medically inoperable, advanced, or metastatic colorectal cancer, including appendiceal adenocarcinoma, for microsatellite instability-high (MSI-H), or deficient mismatch repair (dMMR), or polymerase epsilon/delta (POLE/POLD1) mutation with ultra-hypermutated phenotype tumors.

   3. Nasopharyngeal Carcinoma (NPC)

      Aetna considers toripalimab-tpzi (Loqtorzi) medically necessary when either of the following criteria are met:

      1. The requested medication will be used in combination with cisplatin and gemcitabine for the treatment of unresectable, metastatic or recurrent locally advanced NPC; or
      2. The requested medication will be used as a single agent for treatment of recurrent, unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy.

   4. Non-Small Cell Lung Cancer (NSCLC)

      1. Aetna considers toripalimab-tpzi (Loqtorzi) medically necessary for treatment of advanced NSCLC when there are no EGFR or ALK mutations (unless testing is not feasible due to insufficient tissue) and the requested medication will be used as a first-line treatment in combination with platinum-doublet chemotherapy and then continued as single agent maintenance therapy.
      2. Aetna considers toripalimab-tpzi (Loqtorzi) medically necessary as neoadjuvant treatment if there are no EGFR or ALK mutations (unless testing is not feasible due to insufficient tissue) when used in combination with platinum-doublet chemotherapy and then continued as single agent adjuvant therapy after surgery.

   5. Small Bowel Adenocarcinoma

      Aetna considers toripalimab-tpzi (Loqtorzi) medically necessary as a single agent for treatment of locally unresectable, medically inoperable, advanced or metastatic small bowel adenocarcinoma for microsatellite instability-high (MSI-H), or deficient mismatch repair (dMMR), or polymerase epsilon/delta (POLE/POLD1) mutation with ultra-hypermutated phenotype tumors.

      Aetna considers all other indications as experimental, investigational, or unproven.

3. Continuation of Therapy

   1. Nasopharyngeal Carcinoma

      Aetna considers continuation of toripalimab-tpzi (Loqtorzi) therapy (for up to 24 months total when being used as first line therapy) in members requesting reauthorization for nasopharyngeal carcinoma when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

   2. Neoadjuvant NSCLC

      Aetna considers continuation of toripalimab-tpzi (Loqtorzi) therapy (up to 13 cycles total) in members requesting reauthorization for neoadjuvant treatment of NSCLC who have not experienced disease progression or an unacceptable toxicity.

   3. NSCLC

      Aetna considers continuation of toripalimab-tpzi (Loqtorzi) therapy (for up to 24 months total) in members requesting reauthorization for NSCLC when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

   4. All Other Indications

      Aetna considers continuation of toripalimab-tpzi (Loqtorzi) therapy in members requesting reauthorization for an indication listed in Section II when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Toripalimab-tpzi is supplied as Loqtorzi  240 mg/6 mL (40 mg/mL) solution in a single-dose vial for intravenous infusion.

The recommended dosage is as follows:

For first-line treatment of metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC), in combination with cisplatin and gemcitabine: 

•  240 mg intravenously every three weeks until disease progression, unacceptable toxicity, or up to 24 months.

For previously treated unresectable or metastatic NPC, as a single agent:

• 3 mg/kg intravenously every two weeks until disease progression or unacceptable toxicity.

First infusion: Infuse over 60 minutes.

Subsequent infusions: If no infusion-related reactions occurred during the first infusion, subsequent infusions may be administered over 30 minutes.

Refer to full prescribing information for Loqtorzi for dosage modifications and preparation and administration instructions.

Source: Coherus BioSciences, 2023

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
96413 - 96415	Chemotherapy administration
HCPCS codes covered if selection criteria are met:
J3263	Injection, toripalimab-tpzi, 1 mg
Other HCPCS codes related to the CPB:
Lenalidomide, Pomalidomide –no specific code
J9060	Injection, cisplatin, powder or solution, 10 mg
J9196	Injection, gemcitabine hydrochloride (accord), not therapeutically equivalent to j9201, 200 mg
J9201	Injection, gemcitabine hydrochloride, not otherwise specified, 200 mg
ICD-10 codes covered if selection criteria are met:
C11.0 – C11.9	Malignant neoplasm of nasopharynx [metastatic, recurrent, or unresectable]
C17.0 – C17.9	Malignant neoplasm of small intestine
C18.0 – C18.9	Malignant neoplasm of colon
C19	Malignant neoplasm of rectosigmoid junction
C20	Malignant neoplasm of rectum
C21.0 – C21.8	Malignant neoplasm of anus and anal canal
C34.00 - C34.92	Malignant neoplasm of bronchus and lung [NSCL]

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Background

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

• Loqtorzi is indicated, in combination with cisplatin and gemcitabine, for first-line treatment of adults with metastatic or with recurrent locally advanced nasopharyngeal carcinoma (NPC).
• Loqtorzi is indicated, 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.

Compendial Uses

• Anal Carcinoma
• Colorectal Cancer
• Nasopharyngeal Carcinoma (NPC)
• Non-small Cell Lung Cancer (NSCLC)
• Small Bowel Adenocarcinoma

Toripalimab-tpzi is available as Loqtorzi (Coherus BioSciences, Inc.) and is a programmed death receptor-1 (PD-1) blocking monoclonal antibody. Loqtorzi binds to the PD-1 receptor and blocks its interactions with PD-L1 and PD-L2, releasing PD-1 pathway mediated inhibition of the immune response, including anti-tumor immune response. Blocking PD-1 activity resulted in decreased tumor growth in syngeneic mouse tumor models (Coherus BioSciences, 2024).

Loqtorzi carries the following warnings and precautions according to the prescribing information:

• Immune-mediated adverse reactions: May be severe or fatal and can occur in any organ system or tissue (including immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, immune-mediated dermatologic adverse reactions, and solid organ transplant rejection). Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue based on severity and type of reaction.
• Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue Loqtorzi based on the severity of reaction.
• Complications of allogeneic stem cell transplantation (HSCT): Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody.
• Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective method of contraception.

Loqtorzi carries the following adverse reactions per the prescribing information:

• Loqtorzi in combination with cisplatin and gemcitabine: The most common adverse reactions (≥ 20%) are nausea, vomiting, decreased appetite, constipation, hypothyroidism, rash, pyrexia, diarrhea, peripheral neuropathy, cough, musculoskeletal pain, upper respiratory infection, insomnia, dizziness, and malaise.
• Loqtorzi as a single agent: The most common adverse reactions (≥ 20%) are fatigue, hypothyroidism, and musculoskeletal pain.

On October 27, 2023, the U.S. Food and Drug Administration (FDA) approved toripalimab-tpzi (Loqtorzi) in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC). In addition, the FDA approved Loqtorzi as a single agent for adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy. The FDA approval was based on supporting data from the JUPITER-02 and POLARIS-02 studies, respectively.

Mai and colleagues (2021) evaluated the efficacy of toripalimab-tpzi (Loqtorzi) in combination with cisplatin and gemcitabine in JUPITER-02, 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 were randomized (1:1) to receive Loqtorzi (240 mg [n=146]) or placebo (n=143) in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance with Loqtorzi or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. The primary efficacy outcome was progression-free survival (PFS) and additional efficacy outcome measures included overall response rate (ORR) and overall survival (OS). A statistically significant PFS improvement was observed with a median PFS of 11.7 months versus 8.0 months (hazard ratio [HR] 0.52 [95% Confidence Interval [CI]: 0.36, 0.74], p-value=0.0003) for the Loqtorzi and placebo-containing regimens, respectively. A statistically significant OS improvement was also observed with median OS not reached (95% CI: 38.7 months, not estimable) for the Loqtorzi-containing regimen and 33.7 months (95% CI: 27.0, 44.2) for the placebo-containing regimen (HR 0.63 [95% CI: 0.45, 0.89], p-value=0.0083).

Investigators evaluated the efficacy of toripalimab-tpzi (Loqtorzi) as a single agent in POLARIS-02, an open-label, multicenter, single country, multicohort trial in 172 patients with unresectable 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. Patients received Loqtorzi 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR). The ORR was 21% (95% CI: 15, 28) and median DOR was 14. 9 months (95% CI: 10.3, not estimable) (Coherus BioSciences, 2023; FDA, 2023).

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References