Tislelizumab-jsgr (Tevimbra)

Number: 1057

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 tislelizumab-jsgr (Tevimbra) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of tislelizumab-jsgr (Tevimbra) is required of all Aetna participating providers and members in applicable plan designs. For precertification of tislelizumab-jsgr (Tevimbra), 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 tislelizumab-jsgr (Tevimbra), see Utilization Management Policy on Site of Care for Specialty Drug Infusions. 

1. Exclusions

   Aetna considers members not eligible for Tevimbra 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 tislelizumab-jsgr (Tevimbra) medically necessary as a single agent for subsequent treatment of metastatic anal carcinoma.
      

   2. Esophageal squamous cell carcinoma

      Aetna considers tislelizumab-jsgr (Tevimbra) medically necessary for the treatment of esophageal squamous cell carcinoma in members who are not surgical candidates or have unresectable, recurrent, or metastatic disease when the following criteria are met:

      1. The member has tried prior systemic chemotherapy not including a PD-L1 inhibitor; and
      2. The requested medication will be used as a single agent.

   3. Gastric cancer

      Aetna considers tislelizumab-jsgr (Tevimbra) medically necessary in combination with platinum and fluoropyrimidine-based chemotherapy for first-line treatment of unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (greater than or equal to 1).

   4. Head and neck cancer

      Aetna considers tislelizumab-jsgr (Tevimbra) medically necessary in combination with cisplatin and gemcitabine for subsequent treatment of metastatic nasopharyngeal cancer.

   5. Hepatocellular carcinoma

      Aetna considers tislelizumab-jsgr (Tevimbra) medically necessary as a single agent for the first line treatment of hepatocellular carcinoma when the member is deemed ineligible for resection, transplant, or locoregional therapy.

   6. Histologic (Richter) transformation to diffuse large B-cell lymphoma

      Aetna considers tislelizumab-jsgr (Tevimbra) medically necessary for the treatment of histologic (Richter) transformation to diffuse large B-cell lymphoma in combination with zanubrutinib.

   7. Small bowel adenocarcinoma

      Aetna considers tislelizumab-jsgr (Tevimbra) medically necessary as a single agent for the treatment of unresectable, inoperable, advanced or metastatic small bowel adenocarcinoma for microsatellite instability-high (MSI-H), or mismatch repair deficient (dMMR), or polymerase epsilon/delta (POLE/POLD1) tumors with ultra-hypermutated phenotype (e.g., tumor mutational burden (TMB) greater than 50 mut/Mb).
      

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

3. Continuation of Therapy

   Aetna considers continuation of tislelizumab-jsgr (Tevimbra) therapy medically necessary for treatment 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

Tislelizumab-jsgr is supplied as Tevimbra injection 100 mg/10 mL (10 mg/mL) solution in a single-dose vial for intravenous infusion.

Esophageal and Gastric Cancer

The recommended dose of Tevimbra is 200 mg administered as an intravenous infusion once every 3 weeks, until disease progression or unacceptable toxicity. Administer the first infusion over 60 minutes. If tolerated, subsequent infusions may be administered over 30 minutes.

Source: BeiGene USA, 2024

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
96413	Chemotherapy administration, IV infusion technique; up to 1 hour, single or initial substance/drug
96415	each additional hour (list in addition to code for primary procedure)
HCPCS codes covered if selection criteria are met:
J9329	Injection, tislelizumab-jsgr, 1mg
Other HCPCS codes related to the CPB:
J9022	Injection, atezolizumab, 10 mg
J9023	Injection, avelumab, 10 mg
J9119	Injection, cemiplimab-rwlc, 1 mg
J9173	Injection, durvalumab, 10 mg
J9271	Injection, pembrolizumab, 1 mg
J9299	Injection, nivolumab, 1 mg
ICD-10 codes covered if selection criteria are met:
C11.0 - C11.9	Malignant neoplasm of nasopharynx
C15.3 - C15.9	Malignant neoplasm of esophagus [squamous cell carcinoma]
C16.0	Malignant neoplasm of cardia [Gastroesophageal junction adenocarcinoma]
C17.0 - C17.9	Malignant neoplasm of small intestine [Small bowel adenocarcinoma]
C21.0 - C21.8	Malignant neoplasm of anus and anal canal
C22.0	Liver cell carcinoma
C83.30 - C83.A	Diffuse large B-cell lymphoma [Histologic (Richter) transformation to diffuse large B-cell lymphoma]

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Background

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

• Esophageal cancer

  Tevimbra as a single agent, is indicated for the treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor.

• Gastric cancer

  Tevimbra, in combination with platinum and fluoropyrimidine-based chemotherapy, is indicated for the first-line treatment of adults with unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma (G/GEJ) whose tumors express PD-L1 (≥1).

Compendial Uses

• Anal carcinoma
• Esophageal squamous cell carcinoma
• Head and neck cancer
• Hepatocellular carcinoma
• Histologic (Richter) transformation to diffuse large B-cell lymphoma
• Small bowel adenocarcinoma

Tislelizumab-jsgr is available as Tevimbra (BeiGene USA, Inc.) and is a programmed death receptor-1 (PD 1)-blocking antibody. Tevimbra is an Fc-engineered humanized monoclonal IgG4 kappa antibody produced in recombinant Chinese hamster ovary (CHO) cells. Tevimbra binds to PD-1 ligands PD-L1 and PD-L2, to the PD-1 receptor found on T cells, which inhibits T-cell proliferation and cytokine production. PD-1 ligands are upregulated in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors (BeiGene USA, 2024).

Tevimbra, according to the prescribing information, carries the following warnings and precautions:

• Immune-mediated adverse reactions:

  • Immune-mediated adverse reactions can be severe or fatal and occur in any organ system or tissue, including the following: 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 Tevimbra based on the severity of reaction.
    
    
• Infusion-related reactions: Slow the rate of infusion, interrupt, or permanently discontinue based on severity of infusion reaction.
• Complications of allogeneic hematopoietic 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 possible risk to a fetus and to use of effective contraception.

According to the prescribing information, the most common adverse reactions (≥ 20%), including laboratory abnormalities with Tevimbra are: increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT, and cough.

On March 13, 2024, the U.S. Food and Administration (FDA) approved tislelizumab-jsgr (Tevimbra) as single agent therapy for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-L1 inhibitor. This FDA approval was based on supporting data from the RATIONALE-302 study, a multicenter, randomized, open-label phase III clinical trial (BeiGene, 2024a).

In the RATIONALE-302 trial, Shen and colleagues (2022) evaluated the efficacy and safety of tislelizumab-jsgr (Tevimbra) in adult patients with unresectable advanced or metastatic ESCC who progressed on or after prior systemic chemotherapy. In total, 512 patients were randomized (1:1) to receive intravenous Tevimbra 200 mg every 3 weeks (n=256) or investigator's choice of chemotherapy (ICC) (n=256; paclitaxel (33%), docetaxel (21%), or inrinotecan (46%)). Patients were treated until disease progression assessed by the investigator or unacceptable toxicity.

The primary efficacy endpoint measure was overall survival (OS) in the Intent-to-Treat (ITT) population. Secondary efficacy endpoint measures included investigator-assessed progression-free survival (PFS), overall response rate (ORR), and duration of response (DOR) per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) (BeiGene USA, 2024).

The investigators conducted a final analysis after 410 death events occurred and reported that OS was significantly longer with Tevimbra versus chemotherapy in all patients (median, 8.6 months versus 6.3 months; hazard ratio [HR], 0.70 [95% confidence interval (CI), 0.57 to 0.85]; p = 0.0001). Patients in the Tevimbra treatment arm experienced a higher objective response rate (15.2%; 95% CI [11.1, 20.2]) compared to patients in the ICC arm (6.6%; 95% CI [3.9, 10.4]). The median duration of response was 10.3 months (6.5, 13.2) versus 6.3 months (2.8, 8.5), respectively. Fewer patients experienced ≥ grade 3 treatment-related adverse events (18.8% versus 55.8%) with Tevimbra compared to ICC (BeiGene USA, 2024).

The RATIONALE-302 study demonstrated a statistically significant improvement in OS in patients who received Tezimbra compared with ICC. The investigators concluded that Tezimbra significantly improved OS compared with chemotherapy as second-line therapy in patients with advanced or metastatic ESCC, with a tolerable safety profile (Shen et al., 2022).

On December 27, 2024, the U.S. Food and Drug Administration (FDA) approved tislelizumab-jsgr (Tevimbra), n combination with platinum and fluoropyrimidine-based chemotherapy, for the first-line treatment of unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma (G/GEJ) in adults whose tumors express PD-L1 (≥1). The FDA approval for this expanded indication for first-line G/GEJ cancers was based on supporting data from the RATIONALE-305 study (BeiGene, 2024b).

In the RATIONALE-305 study, randomized, multicenter, placebo-controlled, double-blind, global phase 3 trial, Qiu et al. (2024) evaluated the efficacy and safety of tislelizumab-jsgr (Tevimbra) in patients with HER2-negative previously untreated unresectable or metastatic G/GEJ adenocarcinoma regardless of programmed death-ligand 1 (PD-L1) expression status, who had not received systemic anticancer therapy for advanced disease. Patients were excluded if they had active leptomeningeal disease or uncontrolled brain metastasis, and patients with active autoimmune disease or history of autoimmune diseases, or a medical condition requiring systemic corticosteroids or immunosuppressants (BeiGene USA, 2024).

Patients (n = 997) were randomly assigned 1:1 to receive either Tevimgra 200 mg (n = 501) or placebo (n = 496) intravenously every three weeks in combination with chemotherapy (investigator's choice of oxaliplatin and capecitabine, or cisplatin and 5-fluorouracil) and stratified by region, PD-L1 expression, presence or absence of peritoneal metastases, and investigator's choice of chemotherapy. Treatment continued until disease progression or unacceptable toxicity.

The primary endpoint was overall survival (OS), both in patients with a PD-L1 tumour area positivity (TAP) score of ≥ 5% and in all randomised patients. Safety was assessed in all those who received at least one dose of study treatment. Tevimbra in combination with chemotherapy demonstrated statistically significant improvements and clinically meaningful overall survival (OS) benefit with a median OS of 15.0 months for patients treated with Tevimbra plus chemotherapy versus 12.9 months for patients treated with placebo plus chemotherapy (n=997; Hazard Ration [HR]: 0.80 (95% Confidence Interval [CI]: 0.70, 0.92); p=0.0011), resulting in a 20% reduction in the risk of death (BeiGene, 2024b). Grade 3 or worse treatment related adverse events were noted in 54% (268/498) of patient in the Tevimbra plus chemotherapy group versus 50% (246/494) in the placebo plus chemotherapy group.

The investigators concluded that Tevimbra plus chemotherapy as a primary treatment for G/GEJ adenocarcinoma demonstrated superior OS with a reasonable safety profile versus placebo plus chemotherapy in patients with a PD-L1 TAP score of of ≥ 5%, and in all randomised patients.

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References