Tarlatamab-dlle (Imdelltra)

Number: 1062

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 tarlatamab-dlle (Imdelltra) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

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

1. Criteria for Initial Approval

   Small Cell Lung Cancer

   Aetna considers tarlatamab-dlle (Imdelltra) medically necessary for treatment as a single agent when one of the following is met:

   1. Member has extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy; or 
   2. The requested medication will be used for treatment of brain metastases in small cell lung cancer.

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

2. Continuation of Therapy

   Aetna considers continuation of tarlatamab-dlle (Imdelltra) therapy medically necessary for members requesting reauthorization for an indication listed in the Criteria for Initial Approval section when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Tarlatamab-dlle is supplied as Imdelltra 1 mg  and 10 mg of lyophilized powder in a single-dose vial for reconstitution and further dilution for injection.

• Administer as an intravenous infusion over 1-hour.
• Administer Imdelltra according to the step-up dosing schedule in Table 1 to reduce the risk of cytokine release syndrome.
• Administer concomitant medications as recommended.
• Monitor persons from the start of the Imdelltra infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting.
• Recommend persons to remain within 1-hour of an appropriate healthcare setting for a total of 48 hours from the start of the infusion with Imdelltra following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver.
• Refer to full prescribing information for Imdelltra for preparation and administration instructions.

Table: Recommended Dosage and Schedule of Imdelltra

Dosing Schedule	Day	Dose of Imdelltra	Administration Instructions	Recommended Monitoring
Step-up Dosing Schedule Cycle 1	Day 1Footnote1*	Step-up doseFootnote1* 1 mg	Administer Imdelltra as a 1-hour intravenous infusion in an appropriate healthcare setting.	Monitor patients from the start of the Imdelltra infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting. Recommend that patients remain within 1-hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with Imdelltra accompanied by a caregiver. Observe patients for 6-8 hours post Imdelltra infusion.Footnote2**
	Day 8Footnote1*	10 mgFootnote1*
	Day 15	10 mg
Cycle 2	Day 1 and 15	10 mg		Observe patients for 6-8 hours post Imdelltra infusion.Footnote2**
Cycles 3 and 4	Day 1 and 15	10 mg		Observe patients for 3-4 hours post Imdelltra infusion.Footnote2**
Cycles 5 and subsequent Infusions	Day 1 and 15	10 mg		Observe patients for 2 hours post Imdelltra infusion.Footnote2**

Footnote1*Administer recommended concomitant medications before and after Cycle 1 Imdelltra infusions.

Footnote2**Extended monitoring in a healthcare setting is not required unless the patient experiences Grade ≥ 2 cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome or neurological toxicity during prior treatments.

Source: Amgen, 2024

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
96401 - 96548	Chemotherapy and other highly complex drug or highly complex biologic agent administration
HCPCS codes covered if selection criteria are met:
J9026	Injection, tarlatamab-dlle, 1 mg
ICD-10 codes covered if selection criteria are met:
C34.00 - C34.92	Malignant neoplasm of bronchus and lung [Extensive stage small cell lung cancer (ES-SCLC)]

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Background

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

• Adult patients with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy

Tarlatamab-dlle is available as Imdelltra (Amgen Inc.), a bispecific T-cell engager that binds to delta-like ligand 3 (DDL3) expressed on the surface of cells, including tumor cells, and CD3 expressed on the surface of T-cells. Imdelltra causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells. Imdelltra showed anti-tumor activity in mouse models of SCLC (Amgen, 2024).

According to the prescribing information, Imdelltra carries the following boxed warnings:

• Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving Imdelltra. Initiate treatment with Imdelltra step-up doing schedule to reduce the incidence and severity of CRS. Withhold Imdelltra until CRS resolves or permanently discontinue based on severity.
• Neurologic toxicity including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving Imdelltra. Monitor patients for signs or symptoms of neurologic toxicity including ICANS, during treatment and treat promptly. Withhold Imdelltra until ICANS resolves or permanently discontinue based on severity.

Per the prescribing information, Imdelltra carries the following warnings and precautions and adverse reactions:

• Warnings and precautions

  • Cytopenias: Monitor complete blood counts prior to treatment with Imdelltra, before each dose, and as clinical indicated. Withhold or permanently discontinue based on severity.
  • Infections: Monitor for signs and symptoms of infection; treat appropriately. Withhold or permanently discontinue based on severity.
  • Hepatotoxicity: Monitor liver enzymes and bilirubin prior to treatment with Imdelltra, before each dose, and as clinically indicated. Withhold or permanently discontinue based on severity.
  • Hypersensitivity: Monitor for signs and symptoms of hypersensitivity and treat accordingly. Withhold or permanently or discontinue based on severity.
  • Embryo-fetal toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception.
    
    

• Adverse reactions

  • The most common adverse reactions (≥20%) were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia and nausea.
  • The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increase activated partial thromboplastin time, decreased potassium, increased aspartate aminotransferase, decreased white blood cells, decreased platelets, and increased alanine aminotransferase.

On May 16, 2024, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Imdelltra (tarlatamab-dlle) for extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. The FDA approval was based on supporting data from the DeLLphi-301 study (FDA, 2024).

In the DeLLphi-301 study, an open-label, multicenter, multi-cohort clinical trial, Ahn et al. (2023) evaluated the efficacy and safety or tarlatamab-dlle (Imdelltra) in patients with relapsed/refractory small cell lung cancer (SCLC) with disease progression after receiving previous treatment with platinum-based chemotherapy and at least one other line of prior therapy, an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, and at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The investigators excluded patients with symptomatic brain metastases, evidence of interstitial lung disease or non-infectious pneumonitis, and active immunodeficiency. Ninety-nine patients received Imdelltra at an initial 1 mg dose intravenously on Cycle 1 Day 1 followed by 10 mg on Days 8, 15, and every 2 weeks thereafter until disease progression or unacceptable toxicity. Tumor assessments were performed every 6 weeks for the first 48 weeks and every 12 weeks thereafter. The primary efficacy endpoint measures were overall response rate (ORR) and duration of response (DOR) as evaluated by Blinded Independent Central Review (BCIR) according to RECIST v1.1. ORR was 40% (95% confidence interval [CI]: 31, 51) and median DOR was 9.7 months (range 2.7, 20.7+). Of the 69 patients with available data regarding platinum sensitivity status, the ORR was 52% (95% CI 32, 71) in 27 patients with platinum-resistant SCLC (defined as progression < 90 days after last dose of platinum therapy) and 31% (95% CI 18, 47) in 42 patients with platinum-sensitive SCLC (defined as progression ≥ 90 days after last dose of platinum therapy).

According to National Cancer Institute's Physician Data Query (PDQ) summary on "Small Cell Lung Cancer Treatment (PDQ) - Health Professional Version", SCLC that is extensive-stage is characterized as disease that has spread beyond the supraclavicular areas and is too widespread to be included within the definition of limited-stage disease (LD). Additionally, patients with distant metastases (M1) are always considered to have ED. Conversely, LD is "confined to the hemithorax of origin, mediastinum, or supraclavicular nodes, which can be encompassed within a tolerable radiation therapy port".

The NCCN Guidelines Version 2.2026 Small Cell Lung Cancer characterize extensive-stage small cell lung cancer as "Stage IV (T any, N any, M 1a/b/c), or T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan".

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References