Jazz Pharmaceuticals plc (Nasdaq: JAZZ) has announced promising top-line results from a Phase 3 clinical trial assessing the effectiveness of Zepzelca® (lurbinectedin) combined with the PD-L1 inhibitor atezolizumab (Tecentriq®). This combination therapy was evaluated as a maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC) after undergoing induction therapy with carboplatin, etoposide, and atezolizumab. The findings indicated a statistically significant enhancement in both overall survival (OS) and progression-free survival (PFS), as determined by an independent review facility (IRF), when compared to treatment with atezolizumab alone.
“Each year, about 30,000 new cases of small cell lung cancer (SCLC) are diagnosed in the U.S., with the majority presenting as extensive-stage disease, known for its aggressive nature and poor prognosis,” stated Dr. Luis Paz-Ares, head of medical oncology at Hospital Universitario 12 de Octubre in Madrid, Spain, and principal investigator of the IMforte trial. “These trial outcomes underscore the efficacy of lurbinectedin, which is the most commonly used second-line agent for SCLC in the U.S., especially when paired with standard-care atezolizumab for patients in first-line maintenance treatment. This represents a significant advancement for those facing extensive disease.”
Dr. Rob Iannone, executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, remarked, “The Phase 3 IMforte trial results are highly promising, demonstrating a statistically significant benefit for the Zepzelca and atezolizumab combination in extensive-stage small cell lung cancer patients during first-line maintenance treatment. This regimen has the potential to delay disease progression and extend survival for patients battling this aggressive form of cancer. We are pleased with these clinically meaningful results and intend to submit a supplemental New Drug Application (sNDA) in the first half of 2025 to support this combination in the first-line maintenance setting. Our gratitude extends to the investigators, patients, and our partners at Roche for their contributions to this trial.”
The combination therapy was generally well-tolerated. Preliminary safety data from the ongoing trial aligned with the established safety profiles of Zepzelca and atezolizumab, revealing no new safety signals in the combination arm.
Jazz and Roche plan to present these findings at a future medical conference.
About the IMforte Phase 3 Trial
The IMforte trial (NCT05091567) is a randomized, multicenter Phase 3 maintenance trial investigating the efficacy, safety, and pharmacokinetics of Zepzelca combined with atezolizumab, compared to standard first-line maintenance with atezolizumab alone in adults (≥18 years) with ES-SCLC following induction therapy with carboplatin, etoposide, and atezolizumab. The primary endpoints of the study are OS and IRF-assessed PFS.
The trial comprises two phases: an induction phase and a maintenance phase. Participants were required to show an ongoing response or stable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 after completing four cycles of induction therapy. Eligible participants were then randomized in a 1:1 ratio to receive either lurbinectedin combined with atezolizumab or atezolizumab alone in the maintenance phase.
The trial is sponsored by Roche and co-funded by Jazz Pharmaceuticals. Further details, including eligibility criteria and a list of clinical trial sites, can be accessed at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT05091567).
About Small Cell Lung Cancer
Small cell lung cancer (SCLC) accounts for approximately 13% of lung cancers in the U.S., with around 30,000 new cases diagnosed annually. The risk of developing SCLC is significantly higher among current or former smokers; however, it can also arise from exposure to secondhand smoke, asbestos, certain inhaled chemicals, radiation, and air pollution. A family history of lung cancer can also elevate risk. SCLC is the most aggressive form of lung cancer, rapidly metastasizing to organs like the brain, liver, and bones. While many patients briefly respond to treatment, the cancer often recurs in a more aggressive and treatment-resistant form.
About Zepzelca® (lurbinectedin)
Zepzelca is an alkylating agent that binds to guanine residues within DNA, triggering a series of events that can disrupt the function of DNA-binding proteins, including some transcription factors and DNA repair pathways, ultimately leading to cell cycle disruption and cell death.
The FDA granted accelerated approval for Zepzelca in June 2020 for adult patients with metastatic SCLC who have progressed following platinum-based chemotherapy. This approval was based on the overall response rate (ORR) and duration of response observed in an open-label, monotherapy clinical study. In December 2021, Jazz and PharmaMar announced the initiation of the LAGOON confirmatory Phase 3 clinical trial for Zepzelca in patients with relapsed SCLC. A positive outcome from LAGOON could further validate the benefits of Zepzelca in treating SCLC after progression from first-line platinum-based regimens and support full approval in the U.S.
Zepzelca is prescribed for adults with metastatic SCLC who have not responded to or whose disease has progressed after platinum-based chemotherapy, based on response rate and duration of response.
Important Safety Information for Zepzelca
Before starting Zepzelca, inform your healthcare provider of all medical conditions, particularly if you:
- Have liver or kidney issues.
- Are pregnant or planning to become pregnant, as Zepzelca can harm an unborn baby.
- If capable of becoming pregnant, your healthcare provider should conduct a pregnancy test before treatment and you should use effective birth control during treatment and for six months post-treatment.
- Males with female partners capable of becoming pregnant should also use effective birth control during treatment and for four months afterward.
- Are breastfeeding or planning to breastfeed, as it is unknown if Zepzelca passes into breast milk. You should not breastfeed during treatment and for two weeks after your last dose.
Inform your healthcare provider of all medications, including prescriptions, over-the-counter drugs, vitamins, and supplements, as certain medications may affect Zepzelca’s efficacy.
What to Avoid While Using Zepzelca
Avoid consuming grapefruit, Seville oranges, or products containing grapefruit juice and Seville oranges during Zepzelca treatment.
Potential Serious Side Effects of Zepzelca
Zepzelca may cause serious side effects, including:
- Low Blood Cell Counts: Low levels of neutrophils (neutropenia) and platelets (thrombocytopenia) are common, with potential severity. Patients may experience fever or infection leading to sepsis, which can be fatal. Blood tests are necessary before each treatment to monitor blood cell counts.
- Liver Problems: Increased liver function tests are common and can be severe. Patients should undergo blood tests to check liver function before and during treatment.
- Leakage of Zepzelca: If Zepzelca leaks into surrounding tissues during infusion, it may cause tissue damage. Patients should notify their healthcare provider if they observe leakage or experience redness, swelling, or discomfort at the infusion site.
- Severe Muscle Problems: Patients should inform their healthcare provider of any severe muscle pain or weakness.
Your healthcare provider may pause, reduce the dose, or permanently discontinue Zepzelca if serious side effects occur.
Common Side Effects of Zepzelca
The most frequently reported side effects include:
- Fatigue
- Low white and red blood cell counts
- Increased creatinine (kidney function)
- Elevated liver function tests
- Increased blood sugar levels
- Nausea
- Decreased appetite
- Musculoskeletal pain
- Low albumin levels
- Constipation
- Respiratory issues
- Low sodium and magnesium levels in the blood
- Vomiting
- Cough
- Diarrhea
These are not all potential side effects of Zepzelca. For medical advice regarding side effects, patients are encouraged to consult their doctor. Negative side effects of prescription drugs can be reported to the FDA at www.fda.gov/medwatch or by calling 1-800-FDA-1088. Side effects can also be reported to Jazz Pharmaceuticals at 1-800-520-5568.
For complete Prescribing Information, including Patient Information, please consult your healthcare provider.
ZEPZELCA is a trademark of Pharma Mar, S.A., used by Jazz Pharmaceuticals under license. Tecentriq® (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.
What is Atezolizumab?
Atezolizumab is a prescription medication used to treat adults with extensive-stage small cell lung cancer (SCLC). It may be combined with chemotherapy agents carboplatin and etoposide as the initial treatment.
Important Safety Information
Atezolizumab can trigger the immune system to attack normal organs and tissues, leading to severe or life-threatening complications. Symptoms can arise anytime during treatment or even after it concludes.
Call your healthcare provider immediately if you experience any new or worsening signs or symptoms, such as:
**Kidney
Lung Issues: Cough, shortness of breath, or chest pain.
Intestinal Problems: Diarrhea, frequent bowel movements, black or bloody stools, or severe abdominal pain.
Liver Problems: Yellowing of the skin or eyes, severe nausea, abdominal pain, dark urine, or unusual bleeding/bruising.
Hormonal Issues: Persistent headaches, eye sensitivity, rapid heartbeat, extreme tiredness, weight changes, or mood fluctuations.
