Answers to frequently asked questions about ZEPZELCA

Questions about ZEPZELCA

  • ZEPZELCA was initially granted approval in 2020 as a single agent for second-line treatment of adult patients with SCLC with disease progression on or after platinum-based chemotherapy. In October 2025, the FDA granted approval for ZEPZELCA + atezolizumab for the first-line maintenance treatment of ES-SCLC.1
    ZEPZELCA is an alkylating drug indicated1:

    • in combination with atezolizumab or atezolizumab hyaluronidase-tqjs, for the maintenance treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin, and etoposide
    • for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
    Explore efficacy for ZEPZELCA in first-line. Explore efficacy for ZEPZELCA in second-line.

  • ZEPZELCA is an alkylating agent that binds to guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix towards the major groove.1

    Adduct formation triggers a cascade of events that can affect the subsequent activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in perturbation of the cell cycle and eventual cell death.1

    ZEPZELCA was also shown to inhibit human monocyte activity in vitro and to reduce macrophage infiltration in implanted tumors in mice.1

    Based on preclinical studies, ZEPZELCA may:

    • Affect the tumor microenvironment by inducing apoptosis in tumor-associated macrophages, reducing macrophage infiltration, and altering the expression of key inflammatory and growth factors2-4
    • Activate the cGAS-STING signaling pathway, which mediates multimodal immune activation, leading to immunogenic cell death2,5

    Learn more about the MOA of ZEPZELCA.

  • For information about ongoing studies of ZEPZELCA, contact our Medical Information department at 1-800-520-5568 or via email to medinfo-us@jazzpharma.com.

  • Strong and moderate CYP3A inhibitors: Avoid coadministration with a strong or a moderate CYP3A inhibitor (including grapefruit and Seville oranges) as this increases lurbinectedin systemic exposure, which may increase the incidence and severity of adverse reactions to ZEPZELCA. If the coadministration cannot be avoided, reduce the dose of ZEPZELCA as appropriate.1

    Strong CYP3A inducers: Avoid coadministration with a strong CYP3A inducer as it may decrease systemic exposure to lurbinectedin, which may decrease the efficacy of ZEPZELCA.1

    Learn more about the drug interactions for ZEPZELCA.

  • ZEPZELCA is available for purchase from the authorized Specialty Distributors and group purchasing organizations.

    Get details and contact information on our ordering information page.

Questions about dosing and administration

  • The recommended dose of ZEPZELCA is 3.2 mg/m2 by intravenous infusion over 60 minutes, repeated every 21 days until disease progression or unacceptable toxicity.1

    Initiate treatment with ZEPZELCA only if absolute neutrophil count (ANC) is ≥1,500 cells/mm3 and platelet count is ≥100,000/mm3.1

    For the recommended dosage of atezolizumab or atezolizumab and hyaluronidase-tqjs, refer to the respective Prescribing Information.

    • When administered on the same day, atezolizumab should be administered first, followed by ZEPZELCA

    Learn more about the dosing and administration of ZEPZELCA.

  • There are no additional monitoring requirements specific to ZEPZELCA + atezolizumab.1*

    *Please see the individual product prescribing information for additional information.

    Learn more about the ZEPZELCA + atezolizumab dosing.

  • ZEPZELCA is a hazardous drug. Follow applicable special handling and disposal procedures.1
    Follow these steps for the preparation and administration of ZEPZELCA.

    • Inject 8 mL of Sterile Water for Injection USP into the vial, yielding a solution containing 0.5 mg/mL of ZEPZELCA. Shake the vial until complete dissolution
    • Visually inspect the solution for particulate matter and discoloration. The reconstituted solution is a clear, colorless, or slightly yellowish solution, essentially free of visible particles
    • Calculate the required volume of reconstituted solution as follows:
      Volume (mL) = Body Surface Area (m2) x Individual Dose (mg/m2)/0.5 mg/mL
    • For administration through a central venous line, withdraw the appropriate amount of reconstituted solution from the vial and add to an infusion container containing at least 100 mL of diluent (0.9% Sodium Chloride Injection USP or 5% Dextrose Injection USP)
    • For administration through a peripheral venous line, withdraw the appropriate amount of reconstituted solution from the vial and add to an infusion container containing at least 250 mL of diluent (0.9% Sodium Chloride Injection USP or 5% Dextrose Injection USP)
    • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulate matter is observed, do not administer1
    • ZEPZELCA can be administered with or without an in-line filter. If infusion lines containing in-line filters are utilized for administration of ZEPZELCA, polyethersulfone (PES) in-line filters with pore sizes of 0.22 micron are recommended
      • Do not use in-line nylon membrane filters when the reconstituted ZEPZELCA solution is diluted using 0.9% Sodium Chloride Injection USP. Adsorption of ZEPZELCA to the nylon membrane filters has been observed when 0.9% Sodium Chloride Injection USP is used as the diluent
    • Compatibility with other intravenous administration materials and the diluted ZEPZELCA solution has been demonstrated in the following materials1:
      • Containers: Polyolefin containers (polyethylene, polypropylene, and mixtures)
      • Infusion sets: Polyvinyl chloride (PVC) (non-DEHP-containing), polyurethane, and polyolefin infusion sets (polyethylene, polypropylene, and polybutadiene)
      • Implantable venous access systems: Implantable venous access systems with titanium and plastic resin ports and with polyurethane or silicone intravenous catheters
    • Do not co-administer ZEPZELCA and other intravenous drugs concurrently within the same intravenous line

    Learn more about the preparation and administration of ZEPZELCA.

  • When using ZEPZELCA + atezolizumab1:

    • To reduce the risk of nausea, administer the following pre-infusion medications prior to Cycle 1 and consider for subsequent cycles:
      • Corticosteroids (dexamethasone 8 mg intravenously or equivalent)
      • Serotonin antagonists (ondansetron 8 mg intravenously or equivalent)

    When using ZEPZELCA as a single agent:

    • Consider administering the pre-infusion medications listed above for antiemetic prophylaxis

    Get ordering information for ZEPZELCA.

Questions about ZEPZELCA study designs

  • IMforte was a Phase 3 randomized, multicenter, open-label study in 483 adult patients with ES-SCLC evaluating the efficacy and safety of ZEPZELCA + atezolizumab vs atezolizumab alone as maintenance therapy after first-line induction. The study consisted of an induction phase and a maintenance phase. Patients were randomized to the maintenance phase if they had an ongoing response or stable disease, per RECIST v1.1, and an ECOG PS of 0 or 1 after completion of 4 cycles of atezolizumab (1200 mg IV), carboplatin, and etoposide induction treatment. Randomized patients received either ZEPZELCA (3.2 mg/m2 IV q3w) + atezolizumab (1200 mg IV q3w) [n=242] or atezolizumab (1200 mg IV q3w) [n=241], until disease progression or unacceptable toxicity.1,6

    Dual primary endpoints were OS (time from randomization into the maintenance phase to death from any cause) and IRF-PFS (time from randomization into the maintenance phase to disease progression per RECIST v1.1, as assessed by the IRF, or death from any cause, whichever occurred first).1,6

    Efficacy endpoint assessments started from randomization into the maintenance phase: the median time from the start of induction to the time of randomization was 3.2 months.6

    Learn more about the clinical trial of ZEPZELCA + atezolizumab.

  • The phase 2 study was a multicenter, open-label, multi-cohort trial evaluating ZEPZELCA as a single agent in 105 adult patients with advanced or metastatic SCLC with disease progression on or after platinum-based chemotherapy. Patients received ZEPZELCA 3.2 mg/m2 by intravenous infusion every 21 days (one cycle) for a median of 4 cycles (range: 1 to 24 cycles). The median age was 60 years (range: 40 to 83 years). Baseline ECOG PS was 0–1 in 92% of patients. The major efficacy outcome measure was confirmed investigator-assessed ORR. Additional efficacy outcome measures included duration of response, and an Independent Review Committee assessed ORR using RECIST v1.1,7

    Learn more about the clinical trial of single-agent ZEPZELCA.

  • Both platinum-sensitive and platinum-resistant patients were included in the trial for ZEPZELCA, and both achieved clinically meaningful results. Platinum-resistant patients had recurrence or progression <90 days after the last dose of platinum-containing chemotherapy (CTFI <90 days), while platinum-sensitive patients had recurrence or progression ≥90 days after the last dose of platinum-containing chemotherapy (CTFI ≥90 days).1,7,8

    In an exploratory subgroup analysis, the CTFI groups assessed were:

    Platinum resistant (n=45)3,4 Platinum sensitive (n=60)3,4
    <30 days
    n=21    		 30 to <90 days
    n=24    		 90 to <180 days
    n=40    		 ≥180 days
    n=20
    Platinum resistant (n=45)3,4
    <30 days
    n=21    		 30 to <90 days
    n=24
    Platinum sensitive (n=60)3,4
    90 to <180 days
    n=40    		 ≥180 days
    n=20

    View the study design of the trial for ZEPZELCA in patients with disease progression on or after platinum-based chemotherapy.

Questions about patient support

  • Yes. The JazzCares Program is committed to helping patients get access to Jazz medications and the support they need.

    Learn more about access and support through JazzCares.

  • Yes. There is a guide for patients seeking to engage their healthcare teams in meaningful, informed conversation. This tool can help you clearly communicate with patients about treatment with ZEPZELCA + atezolizumab.

    Download the ZEPZELCA doctor discussion guide in English.

cGAS=cyclic GMP-AMP synthase; CTFI=chemotherapy-free interval; CYP3A=cytochrome P450 3A; DEHP=Di(2-ethylhexyl)phthalate; DNA=deoxyribonucleic acid; ECOG PS=Eastern Cooperative Oncology Group performance status; ES-SCLC=extensive-stage small cell lung cancer; FDA=Food and Drug Administration; MOA=mechanism of action; mSCLC=metastatic small cell lung cancer; ORR=objective response rate; PD-L1=programmed death-ligand 1; q3w=every 3 weeks; RECIST=Response Evaluation Criteria in Solid Tumors; SCLC=small cell lung cancer; STING=stimulator of interferon genes; USP=United States Pharmacopeia.

INDICATIONS

ZEPZELCA (lurbinectedin) for injection 4 mg, in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, is indicated for the maintenance treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide.

ZEPZELCA (lurbinectedin) for injection 4 mg, as a single agent, is indicated for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Myelosuppression

ZEPZELCA can cause severe and fatal myelosuppression including febrile neutropenia and sepsis, thrombocytopenia and anemia.

Administer ZEPZELCA only to patients with baseline neutrophil count of at least 1,500 cells/mm3 and platelet count of at least 100,000/mm3. To reduce the risk of febrile neutropenia during treatment with ZEPZELCA in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, administer granulocyte colony-stimulating factor (G-CSF). Monitor blood counts including neutrophils, red blood cells and platelets prior to each ZEPZELCA administration. For neutrophil count less than 500 cells/mm3 or any value less than lower limit of normal, the use of G-CSF is recommended. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.

  • ZEPZELCA with Intravenous Atezolizumab
    • In the IMforte study, primary prophylaxis of G-CSF was administered to 84% of patients. Based on laboratory values, decreased neutrophils occurred in 36%, including 18% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased neutrophil cells was 31 days and a median duration of 10 days. Febrile neutropenia occurred in 1.7%. Sepsis occurred in 1%. There were 7 fatal infections: pneumonia (n=3), sepsis (n=3), and febrile neutropenia (n=1).
    • Based on laboratory values, decreased platelets occurred in 54%, including 15% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased platelet cells was 31 days and a median duration of 12 days.
    • Based on laboratory values, decreased hemoglobin occurred in 51%, including 13% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased hemoglobin was 64 days and a median duration of 8 days.
  • ZEPZELCA as a Single-Agent
    • In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA as a single agent, Grade 3 or 4 neutropenia occurred in 41% of patients, with a median time to onset of 15 days and a median duration of 7 days. Febrile neutropenia occurred in 7% of patients. Sepsis occurred in 2% of patients and was fatal in 1% (all cases occurred in patients with solid tumors other than SCLC). Grade 3 or 4 thrombocytopenia occurred in 10%, with a median time to onset of 10 days and a median duration of 7 days. Grade 3 or 4 anemia occurred in 17% of patients.

Hepatotoxicity

ZEPZELCA can cause hepatotoxicity which may be severe.

Monitor liver function tests prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.

  • ZEPZELCA with Intravenous Atezolizumab
    • In the IMforte study, based on laboratory values, increased alanine aminotransferase (ALT) occurred in 25%, including 3% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. Increased aspartate aminotransferase (AST) occurred in 24% including 3% Grade 3 or Grade 4. The median time to onset of Grade ≥3 elevation in transaminases was 52 days (range: 6 to 337).
  • ZEPZELCA as a Single-Agent
    • In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA as a single agent, Grade 3 elevations of ALT and AST were observed in 6% and 3% of patients, respectively, and Grade 4 elevations of ALT and AST were observed in 0.4% and 0.5% of patients, respectively. The median time to onset of Grade ≥3 elevation in transaminases was 8 days (range: 3 to 49), with a median duration of 7 days.

Extravasation Resulting in Tissue Necrosis

Extravasation of ZEPZELCA can cause skin and soft tissue injury, including necrosis requiring debridement. Consider use of a central venous catheter to reduce the risk of extravasation, particularly in patients with limited venous access. Monitor patients for signs and symptoms of extravasation during the ZEPZELCA infusion. If extravasation occurs, immediately discontinue the infusion, remove the infusion catheter, and monitor for signs and symptoms of tissue necrosis. The time to onset of necrosis after extravasation may vary.

  • ZEPZELCA with Intravenous Atezolizumab
    • In the IMforte study, extravasation resulting in skin necrosis occurred in one patient who received ZEPZELCA in combination with atezolizumab.

Administer supportive care and consult with an appropriate medical specialist as needed for signs and symptoms of extravasation. Administer subsequent infusions at a site that was not affected by extravasation.

Rhabdomyolysis

Rhabdomyolysis has been reported in patients treated with ZEPZELCA.

Monitor creatine phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold or reduce the dose based on severity.

  • ZEPZELCA with Intravenous Atezolizumab
    • In the IMforte study, among 235 patients who had a creatine phosphokinase laboratory evaluation, increased creatine phosphokinase occurred in 9% who received ZEPZELCA in combination with atezolizumab.

Embryo-Fetal Toxicity

ZEPZELCA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 4 months after the last dose.

Lactation

There are no data on the presence of ZEPZELCA in human milk, however, because of the potential for serious adverse reactions from ZEPZELCA in breastfed children, advise women not to breastfeed during treatment with ZEPZELCA and for 2 weeks after the last dose.

ADVERSE REACTIONS

  • ZEPZELCA with Intravenous Atezolizumab
    • Serious adverse reactions occurred in 31% of patients receiving ZEPZELCA in combination with atezolizumab. Serious adverse reactions occurring in >2% were pneumonia (2.5%), respiratory tract infections (2.1%), dyspnea (2.1%), and decreased platelet count (2.1%). Fatal adverse reactions occurred in 5% of patients receiving ZEPZELCA with atezolizumab including pneumonia (3 patients), sepsis (3 patients), cardio-respiratory arrest (2 patients), myocardial infarction (2 patients), and febrile neutropenia (1 patient).
    • The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received ZEPZELCA with atezolizumab were decreased lymphocytes (55%), decreased platelets (54%), decreased hemoglobin (51%), decreased neutrophils (36%), nausea (36%), and fatigue/asthenia (32%).
  • ZEPZELCA as a Single-Agent
    • Serious adverse reactions occurred in 34% of patients who received ZEPZELCA. Serious adverse reactions in ≥3% of patients included pneumonia, febrile neutropenia, neutropenia, respiratory tract infection, anemia, dyspnea, and thrombocytopenia.
    • The most common adverse reactions, including laboratory abnormalities, (≥20%) are leukopenia (79%), lymphopenia (79%), fatigue (77%), anemia (74%), neutropenia (71%), increased creatinine (69%), increased alanine aminotransferase (66%), increased glucose (52%), thrombocytopenia (37%), nausea (37%), decreased appetite (33%), musculoskeletal pain (33%), decreased albumin (32%), constipation (31%), dyspnea (31%), decreased sodium (31%), increased aspartate aminotransferase (26%), vomiting (22%), decreased magnesium (22%), cough (20%), and diarrhea (20%).

DRUG INTERACTIONS

Effect of CYP3A Inhibitors and Inducers

Avoid coadministration with a strong or a moderate CYP3A inhibitor (including grapefruit and Seville oranges) as this increases lurbinectedin systemic exposure which may increase the incidence and severity of adverse reactions to ZEPZELCA. If coadministration cannot be avoided, reduce the ZEPZELCA dose as appropriate.

Avoid coadministration with a strong CYP3A inducer as it may decrease systemic exposure to lurbinectedin, which may decrease the efficacy of ZEPZELCA.

GERIATRIC USE

  • ZEPZELCA with Intravenous Atezolizumab
    • Of the 242 patients with ES-SCLC treated with ZEPZELCA and atezolizumab in IMforte, 124 (51%) patients were 65 years of age and older, while 29 (12%) patients were 75 years of age and older. No overall differences in effectiveness were observed between older and younger patients. There was no overall difference in the incidence of serious adverse reactions in patients ≥65 years of age and patients <65 years of age (33% vs. 29%, respectively). There was a higher incidence of Grade 3 or 4 adverse reactions in patients ≥65 years of age compared to younger patients (45% vs. 31%, respectively).
  • ZEPZELCA as a Single-Agent
    • Of the 105 patients with SCLC administered ZEPZELCA in clinical studies, 37 (35%) patients were 65 years of age and older, while 9 (9%) patients were 75 years of age and older. No overall difference in effectiveness was observed between patients aged 65 and older and younger patients.
    • There was a higher incidence of serious adverse reactions in patients ≥65 years of age than in patients <65 years of age (49% vs. 26%, respectively). The serious adverse reactions most frequently reported in patients ≥65 years of age were related to myelosuppression and consisted of febrile neutropenia (11%), neutropenia (11%), thrombocytopenia (8%), and anemia (8%). There was a higher incidence of Grade 3 or 4 adverse reactions in patients ≥65 years of age compared to younger patients (76% vs. 50%, respectively).

HEPATIC IMPAIRMENT

Avoid administration of ZEPZELCA in patients with severe hepatic impairment. If administration cannot be avoided, reduce the dose. Monitor for increased adverse reactions in patients with severe hepatic impairment.

Reduce the dose of ZEPZELCA in patients with moderate hepatic impairment. Monitor for increased adverse reactions in patients with moderate hepatic impairment.

No dose adjustment of ZEPZELCA is recommended for patients with mild hepatic impairment.

Please see full Prescribing Information.

References: 1. ZEPZELCA (lurbinectedin) Prescribing Information. Jazz Pharmaceuticals, Inc. 2. Calles A, Calvo E, Santamaría Nuñez G, et al. Unveiling the mechanism of lurbinectedin's action and its potential in combination therapies in small cell lung cancer. Mol Cancer Ther. 2025;24(6):828-839. 3. Belgiovine C, Bello E, Liguori M, et al. Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models. Br J Cancer. 2017;117(5):628–638. 4. Dumoulin DW, Cantini L, Cornelissen R, et al. Lurbinectedin shows clinical activity and immune-modulatory functions in patients with pre-treated small cell lung cancer and malignant pleural mesothelioma. Eur J Cancer. 2022;172:357–366. 5. Chakraborty S, Sen U, Ventura K, et al. Lurbinectedin sensitizes PD-L1 blockade therapy by activating STING-IFN signaling in small-cell lung cancer. Cell Rep Med. 2024;5(12):101852. 6. Paz-Ares L, Borghaei H, Liu SV, et al. Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2025;405(10495):2129​–​2143. 7. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21(5):645–654. 8. Data on file-REF-23026. Jazz Pharmaceuticals, Inc.