Penpulimab-kcqx

Number: 1080

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 penpulimab-kcqx for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

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

1. Exclusions 

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

2. Criteria for Initial Approval

   Nasopharyngeal Carcinoma (NPC)

   Aetna considers penpulimab-kcqx medically necessary for the treatment of non-keratinizing nasopharyngeal carcinoma when either of the following criteria is met:

   1. The requested medication will be used as first-line treatment of recurrent or metastatic disease in combination with either cisplatin or carboplatin and gemcitabine for six cycles and then as a single agent; or
   2. The requested medication will be used as a single agent for the treatment of metastatic disease with progression on or after platinum-based chemotherapy and at least one other prior line of therapy.

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

3. Continuation of Therapy

   Aetna considers continuation of penpulimab-kcqx therapy medically necessary (up to 24 months total) 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

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

Penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine:

• 200 mg intravenously over 60 minutes every 3 weeks until disease progression or unacceptable toxicity, for a maximum of 24 months.

Penpulimab-kcqx as a single agent:

• 200 mg intravenously over 60 minutes every 2 weeks until disease progression or unacceptable toxicity, for a maximum of 24 months.

Dilute prior to administration.

Source: Akeso Biopharma Co., 2025

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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:
Penpulimab-kcqx – no specific code
Other HCPCS codes related to the CPB:
J9045	Injection, carboplatin, 50 mg
J9060	Injection, cisplatin, powder or solution, 10 mg
J9196	Injection, gemcitabine hydrochloride (accord), not therapeutically equivalent to j9201, 200 mg
J9198	Injection, gemcitabine hydrochloride, (infugem), 100 mg
J9201	Injection, gemcitabine hydrochloride, not otherwise specified, 200 mg
J9263	Injection, oxaliplatin, 0.5 mg
ICD-10 codes covered if selection criteria are met:
C11.0 – C11.9	Malignant neoplasm of nasopharynx [non-keratinizing]

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Background

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

• Nasopharyngeal Carcinoma (NPC)

  • Penpulimab-kcqx is indicated in combination with either cisplatin or carboplatin and gemcitabine for the first-line treatment of adults with recurrent or metastatic non-keratinizing NPC.
  • Penpulimab-kcqx is indicated as a single agent for the treatment of adults with metastatic non-keratinizing NPC and disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy.

Penpulimab-kcqx is a humanized monoclonal IgG1 antibody which is a programmed death receptor-1 (PD 1)-blocking antibody. Penpulimab-kcqx binds to PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, releasing PD-1 pathway-mediated inhibition of the immune response, including anti-tumor immune response. In  murine tumor models, blocking PD-1 activity resulted in decreased tumor growth (Akeso Biopharma Co., 2025).

According to the prescribing information, penpulimab-kcqx carries the following warnings and precautions and adverse reactions:

Warnings and precautions:

• Immune-mediated adverse reactons

  • Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis and hepatotoxicity, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and 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 penpulimab-kcqx based on severity and type of reaction.
    
    
• Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue penpulimab-kcqx based on the severity of the 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 potential risk to a fetus and to use effective contraception.

Adverse reactions:

• Penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine: The most common adverse reactions (≥20%) were nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, cough, COVID-19 infection, fatigue, rash, and pyrexia.
• Penpulimab-kcqx as a single agent: The most common adverse reactions (≥20%) were anemia and hypothyroidism.

On April 23, 2025, the U.S. Food and Drug Administration (FDA) approved penpulimab-kcqx with cisplatin or carboplatin and gemcitabine for the first-line treatment ofadults with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC). Additionally, the FDA approved penpulimab-kcqx as a single agent for adults with metastatic non-keratinizing NPCwith disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. The FDA approval was based on supported data from the Study AK105-304 and Study AK105-202 (FDA, 2025).

In Study AK105-304, a randomized, double-blind, multi-center trial, investigators evaluated the efficacy of penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine in 291 patients with recurrent or metastatic NPC who had not received previous systemic chemotherapy for recurrent of metastatic disease. Eligible patients were required to have recurrent NPC with local-regional recurrence and/or distant metastasis occurring ≥ 6 months after completion of curative intent treatment or to have primary metastatic NPC not suitable for local therapy at the time of diagnosis. Ineligible patients were those with autoimmune disease, other than stable hypothyroidism or Type 1 diabetes, and patients who required systemic immunosuppression. Histological subtypes of NPC included 96% non-keratinizing, 0.7% keratinizing squamous cell carcinoma, and 3.4% did not have the subtype identified (Akeso Biopharma Co., 2025).

Patients were randomized (1:1) to receive either:

• Penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, every 3 weeks, for up to 6 cycles, followed by single-agent penpulimab-kcqx every 3 weeks until disease progression or unacceptable toxicity, for a maximum of 24 months; or
• Placebo in combination with either cisplatin or carboplatin and gemcitabine, every 3 weeks for up to 6 cycles, followed by single-agent placebo every 3 weeks until disease progression or unacceptable toxicity, for a maximum of 24 months.

All regimens were administered intravenously (Akeso Biopharma Co., 2025).

The major efficacy outcome measure was progression-free survival (PFS), assessed by a Blinded Independent Review Committee according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The key efficacy outcome measure was overall survival (OS) (Akeso Biopharma Co., 2025).

Median PFS was 9.6 months (95% Confidence Interval [CI]: 7.1, 12.5) in the penpulimab-kcqx arm and 7.0 months (95% CI: 6.9, 7.3) in the placebo arm (hazard ratio [HR] 0.45 [95% CI:0.33, 0.62], two-sided p-value <0.0001), with 31% and 11% of patients alive and progression-free after 12 months of follow-up in the penpulimab-kcqx and placebo arms, respectively. OS results were not mature with 70% of pre-specified OS events observed in the overall population (Akeso Biopharma Co., 2025; FDA, 2025).

In Study AK105-202, an open-label, multicenter, single-arm trial conducted in a single country, investigators evaluated the efficacy of single-agent penpulimab-kcqx in 125 patients with unresectable or metastatic non-keratinizing NPC and who had disease progression after platinum-based chemotherapy and at least one other line of therapy. Ineligible patients were those with autoimmune disease or a medical condition that required immunosuppression (Akeso Biopharma Co., 2025).

Patients received single-agent penpulimab-kcqx 200 mg intravenously every 2 weeks until disease progression or unacceptable toxicity, for a maximum of 24 months (Akeso Biopharma Co., 2025).

The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) according to RECISTv1.1 as assessed by an Independent Radiology Review Committee (IRRC) (Akeso Biopharma Co., 2025).

The ORR was 28% (95% CI: 20, 37) and median DOR was not reached (95% CI: 9.2, not estimable) (Akeso Biopharma Co., 2025; FDA, 2025).

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References