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FDA Approves Novocure’s Optune Lua® for the Treatment of Metastatic Non-Small Cell Lung Cancer

On October 15, 2024 Novocure (NASDAQ: NVCR) reported that the U.S. Food and Drug Administration (FDA) has approved Optune Lua for concurrent use with PD-1/PD-L1 inhibitors or docetaxel, for the treatment of adult patients with metastatic non-small cell lung cancer (mNSCLC) who have progressed on or after a platinum-based regimen (Press release, NovoCure, OCT 15, 2024, View Source [SID1234647215]).

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"Novocure is committed to extending survival in some of the most aggressive and difficult to treat cancers. The approval of Optune Lua brings a new and urgently needed option for people with metastatic NSCLC who have progressed while on or after platinum-based chemotherapy," said Asaf Danziger, CEO, Novocure. "We are grateful to the patients, caregivers, investigators and healthcare providers who supported the clinical trials that led to this approval."

Optune Lua is a portable device that produces alternating electric fields known as tumor treating fields (TTFields), which are delivered through non-invasive, wearable arrays. TTFields exert physical forces on the electrically charged components of dividing cancer cells, resulting in cell death.

"There have been a number of important advances in first-line treatment for NSCLC, but this is an aggressive disease, and most patients will develop progression, with limited effective treatment options in second line and beyond," said Ticiana Leal, MD, Associate Professor and Director of the Thoracic Oncology Program at the Winship Cancer Institute of Emory University School of Medicine and primary investigator of the LUNAR study. "The overall survival results we observed with Optune Lua in the LUNAR study mark the first substantial improvement in more than 8 years in this patient population which, when combined with Optune Lua’s lack of systemic toxicity, make this a compelling development for many patients and their physicians who need better treatment options for this advanced disease."

"We are excited patients with metastatic NSCLC have more options, which they urgently need," said GO2 for Lung Cancer Chief Patient Officer Danielle Hicks. "The fight against lung cancer is always evolving, and the number of people affected by this disease is underappreciated. That is why Novocure’s commitment to advancing treatment is exciting for the whole lung cancer community."

Data Supporting the Optune Lua Approval

The Phase 3 LUNAR study was a prospective, randomized, open-label, multicenter study that compared the use of Optune Lua concurrent with PD-1/PD-L1 inhibitors or docetaxel (experimental arm) to PD-1/PD-L1 inhibitors or docetaxel alone (control arm) for patients with metastatic NSCLC who progressed during or after platinum-based therapy.

The primary endpoint of the study was achieved demonstrating a statistically significant and clinically meaningful 3.3-month (P=0.04) extension in median overall survival (OS) for patients treated with Optune Lua concurrently with a PD-1/PD-L1 inhibitor or docetaxel (n=145). The group treated with Optune Lua concurrently with a PD-1/PD-L1 inhibitor or docetaxel had a median OS of 13.2 months (95% CI, 10.3 to 15.5 months) compared to a median OS of 9.9 months (95% CI, 8.2 to 12.2 months) in the PD-1/PD-L1 inhibitor or docetaxel treated group (n=146).

The LUNAR study included two pre-specified powered secondary endpoints. The first secondary endpoint, which met statistical significance, assessed median OS in patients treated with Optune Lua concurrently with a PD-1/PD-L1 inhibitor versus a PD-1/PD-L1 inhibitor alone. The second secondary endpoint, which showed a positive trend but did not meet statistical significance, assessed Optune Lua concurrently with docetaxel versus docetaxel alone.

Patients randomized to Optune Lua and a PD-1/PD-L1 inhibitor (n=70) demonstrated a median OS of 19.0 months (95% CI, 10.6 to 28.2 months) compared to a median OS of 10.8 months (95% CI, 8.3 to 17.6 months) in patients treated a with PD-1/PD-L1 inhibitor alone (n=71), which was a statistically significant extension in median OS of more than 8.0 months (P=0.02).

Patients randomized to receive Optune Lua and docetaxel (n=75) had a median OS of 11.1 months (95% CI, 8.2 to 13.9 months) compared to a median OS of 8.9 months (95% CI, 6.5 to 11.3 months) in patients treated with docetaxel alone (n=75). This 2.2 month extension in median OS did not provide a statistically significant demonstrated benefit, but did show a positive trend.

Device-related adverse events (AEs) occurred in 63.1% of patients (n=89), these were skin-related disorders under the transducer arrays. The majority of these events were low grade (Grade 1 – 2), with only 4% (n=6) experiencing Grade 3 skin toxicity that required a break from treatment. There were no Grade 4 or Grade 5 toxicities related to Optune Lua, and no device-related AEs that caused death.

Baseline patient characteristics were well balanced between cohorts: median age was 65 years (range, 22-86); 66% male, 34% female; 96% of patients had an ECOG performance status of 0-1. PD-L1 expression data were collected from 83% of patients (69 of 83 patients) enrolled at U.S. sites and were well balanced across the four cohorts.

Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the most common cause of cancer-related death worldwide1, and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. It is estimated that approximately 193,000 patients are diagnosed with NSCLC each year in the U.S.

Physicians use different combinations of surgery, radiation and pharmacological therapies to treat NSCLC, depending on the stage of the disease. Surgery, which may be curative in a subset of patients, is usually used in early stages of the disease. Since 1991, radiation with a combination of platinum-based chemotherapy drugs has been the first-line standard of care for locally advanced or metastatic NSCLC. Certain immune checkpoint inhibitors, including both PD-1 and PD-L1 inhibitors, have been approved for the first-line treatment of NSCLC and the standard of care in this setting continues to evolve rapidly.

It is estimated that approximately 30,000 patients actively seek treatment for stage 4 NSCLC after progressing during or after platinum-based therapy each year in the U.S. The standard of care for second-line treatment is also evolving and may include platinum-based chemotherapy for patients who received immune checkpoint inhibitors as their first-line regimen, pemetrexed, docetaxel or immune checkpoint inhibitors.

What is Optune Lua approved to treat?

Optune Lua is a wearable, portable, FDA-approved device used together with PD-1/PD-L1 inhibitors (immunotherapy) or docetaxel. It is indicated for adult patients with metastatic non-small cell lung cancer (mNSCLC) who have progressed on or after a platinum-based regimen.

Important Safety Information

Who should not use Optune Lua?

Optune Lua for mNSCLC is not for everyone. Talk to your doctor if you have:

An electrical implant. Use of Optune Lua together with electrical implants has not been tested and may cause the implanted device not to work properly
A known sensitivity to gels like the gel used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes. In this case, skin contact with the gel used with Optune Lua may commonly cause increased redness and itching, and rarely may even lead to severe allergies such as a fall in blood pressure and difficulty breathing
Do not use Optune Lua if you are pregnant or are planning to become pregnant. It is not known if Optune Lua is safe or effective during pregnancy.

What should I know before using Optune Lua?

Optune Lua should only be used after receiving training from qualified personnel, such as your doctor, a nurse, or other medical staff who have completed a training course given by Novocure, the maker of Optune Lua.

Do not use any parts that did not come with Optune Lua Treatment Kit sent to you by Novocure or given to you by your doctor
Do not get the device or transducer arrays wet
Please be aware that Optune Lua has a cord that plugs into an electrical socket. Be careful of tripping when it’s connected
If you have an underlying serious skin condition where the transducer arrays are placed, discuss with your doctor whether this may prevent or temporarily interfere with Optune Lua treatment
What are the possible side effects of Optune Lua?

The most common side effects of Optune Lua when used together with certain immunotherapy and chemotherapy drugs were dermatitis, pain in the muscles, bones, or joints, fatigue, anemia, alopecia (hair loss), dyspnea, nausea, cough, diarrhea, anorexia, pruritus (itching), leukopenia, pneumonia, respiratory tract infection, localized edema (swelling), rash, pain, constipation, skin ulcers, hypokalemia (low potassium levels), hypoalbuminemia (low albumin levels), hyponatremia (low sodium levels), and dysphagia (difficulty swallowing).

Other potential adverse effects associated with the use of Optune Lua include treatment related skin irritation, allergic reaction to the adhesive or to the gel, overheating of the array leading to pain and/or local skin burns, infections at site where the arrays make contact with the skin, local warmth and tingling sensation beneath the arrays, medical device site reaction, muscle twitching, and skin breakdown/skin ulcer. Talk to your doctor if you have any of these side effects or questions.

About Tumor Treating Fields

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. These multiple, distinct mechanisms work together to target and kill cancer cells. Due to these multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or targeted therapies in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors.

LOMOND THERAPEUTICS ANNOUNCES FDA CLEARANCE OF IND APPLICATION FOR PHASE 1 STUDY OF LONITOCLAX, A SELECTIVE BCL2 INHIBITOR, FOR CHRONIC LYMPHOCYTIC LEUKEMIA, SMALL LYMPHOCYTIC LYMPHOMA, AND SELECT LOW-GRADE LYMPHOMAS

On October 15, 2024 Lomond Therapeutics, a subsidiary of Eilean Therapeutics LLC, a biopharmaceutical company dedicated to discovering and developing best-in-class and first-in-class small molecule inhibitors to target escape mutations in hematologic and solid malignancies, reported that the U.S. Food and Drug Administration (FDA) has cleared Lomond’s Investigational New Drug (IND) application for a Phase 1 multicenter study evaluating the feasibility, safety, and efficacy of lonitoclax in patients with relapsed/refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, and select low-grade lymphomas (Press release, Lomond Therapeutics, OCT 15, 2024, View Source [SID1234647214]).

"We are pleased with the progress we have made to date and excited with the FDA clearance of our IND to initiate patient testing of lonitoclax," said Dr. Iain Dukes, Chief Executive Officer of Eilean Therapeutics. "Given the highly differentiated pre-clinical and healthy volunteer profile of lonitoclax, we believe that lonitoclax has the potential to be the best-in-class BCL-2 inhibitor and look forward to working with the leukemia and lymphoma community in initiating our Phase 1 clinical study."

About Lonitoclax

Lonitoclax has earlier reported novel binding, best-in-class potency and selectivity against BCL-2, a key pro-survival protein that is overexpressed in many cancers. This clinical candidate demonstrated equivalent in vivo anti-tumor efficacy to venetoclax in B cell and myeloid malignancy cell lines and in vivo models. Compared to venetoclax, lonitoclax exhibits significantly less suppression of non-malignant immune cell populations, a result that suggests superior selectivity, and an improved safety profile. Lonitoclax has previously completed a series of healthy volunteer studies where no safety signals were observed at exposures where ex vivo activation of caspase in CLL primary cells was observed, a surrogate marker of BCL-2 inhibition in tumors. This emphasizes important advantages over venetoclax and venetoclax-like molecules in safety, tolerability, and feasibility of outpatient treatment, enabling the molecule to safely target AML and CLL patients alone and in combination with other targeted therapies.

Lutris Pharma Completes Enrollment in Phase 2 Trial of LUT014 for the Treatment of EGFRI-Induced Acneiform Rash in Patients with Metastatic Colorectal Cancer

On October 15, 2024 Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing cutaneous dose limiting toxicity, reported that it has completed enrollment in the phase 2 trial of lead compound, LUT014, a topically-applied novel B-Raf inhibitor, for patients with metastatic colorectal cancer (mCRC) treated with epidermal growth factor receptor (EGFR) inhibitor therapy who develop dose-limiting acneiform rash (Press release, Lutris Pharma, OCT 15, 2024, View Source [SID1234647213]). Topline results are expected in first quarter of2025.

The phase 2, randomized, double-blind, placebo-controlled trial has enrolled a total of 117 subjects at 20 international sites, including Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center and Dana Farber Cancer Institute. The trial is evaluating the efficacy and safety of two strengths of LUT014 gel, 0.03% or 0.10%, applied once daily for 4 weeks, compared to placebo (with a randomization of 1:1:1), in patients with mCRC who develop Grade 2 or non-infected Grade 3 EGFR inhibitor-induced acneiform rash, with a 4-week follow up period. During an optional open label extension period for the placebo group, eligible subjects received the 0.03% concentration of LUT014.

The study’s primary endpoint is the proportion of subjects in each treatment group who achieve treatment success, defined as an improvement (decrease) of at least one grade in the severity of the acneiform lesions from baseline to Day 28, based on common terminology criteria for adverse events (CTCAE) V5.0 skin and subcutaneous tissue disorders grading scale or, an improvement (increase) of at least 5 points in the total score for the skin-specific (first 13 questions) of the functional assessment of cancer therapy epidermal growth factor receptor inhibitor 18 (FACT-EGFRI-18) health related quality of life (HRQoL) questionnaire, from baseline to Day 28. Key secondary endpoints include adherence to EGFR inhibitor treatment.

"Enrollment of the last patient is an important milestone for Lutris Pharma and in the progress of the international phase 2 trial of LUT014," stated Antoni Ribas, M.D., Ph.D., Chairman and Founder of Lutris Pharma. "Although EGFR inhibitors are critical treatment options, approximately 75% of patients with mCRC receiving such therapy experience acneiform rash, which can be so disruptive to quality of life that many of these patients do not receive the optimal treatment against their cancer, either due to dose reduction or even discontinuation of the anti-EGFR therapy, caused by the rash. By reversing the inhibitory effect of anti-EGFR therapy on downstream signaling in the skin cells, we believe that LUT014 has the potential to address a toxicity of otherwise effective therapeutic regimens and can have a favorable impact for patients who currently have no other treatment options.

Dr. Ribas continued, "having generated positive phase 1 results in patients with mCRC, demonstrating safety, preliminary efficacy a dose response and a therapeutic benefit in all patients, we look forward to reporting topline results from the phase 2 study early next year and are planning present them at a major medical meeting."

"Reporting data on the use of LUT014 to treat acneiform rash induced by anti-EGFR inhibitors will be timely, given the encouraging data generated with new classes of EGFR inhibitors being developed for the treatment of cancer" added Noa Shelach, Ph.D., Chief Executive Officer of Lutris Pharma. "These active anticancer agents have the same class-effect dose limiting skin toxicities that could be addressed with the topical application of LUT014, potentially broadening the clinical benefit to patients with cancer."

For more information on this clinical trial, please visit: www.clinicaltrials.gov, NCT04759664.

About EGFR Inhibitor-Induced Rash
EGFR is a receptor on the surface of cells which is expressed in many normal epithelial tissues, including skin. The EGFR signaling pathway is one of the key pathways that regulate growth, survival, proliferation, and differentiation of cells. B-Raf is a protein encoded by the BRAF gene and is a downstream effector component of EGFR signaling pathway. EGFR has been shown to be over-activated in various human cancers, including colorectal, lung, head and neck, urinary bladder, pancreatic and breast cancers, eliciting downstream phosphorylation and activation of the MAP Kinase pathway.

Drugs called EGFR inhibitors can block the EGFR signal responsible for cell growth. Among the various types of pharmacological therapies for cancer, EGFR inhibitors are increasingly being used both as primary therapy as well as in patients who have failed prior chemotherapy. Although effective as anti-cancer therapy leading to tumor shrinkage, EGFR inhibitors have many adverse reactions associated with their use. The majority of patients treated with EGFR inhibitors will experience adverse dermatological side effects typically manifested as a papulopustular skin rash, also known as acneiform lesions, which can impact quality of life and affect adherence to therapy.

About LUT014
LUT014 is a novel B-Raf inhibitor which is applied topically on the skin. When the B-Raf protein is mutated, as is the case in some human cancers such as melanoma, blocking this pathway leads to apoptosis of the cells and tumor shrinkage. However, when the same pathway is blocked in normal, non-mutated cells, the opposite happens: the MAPK pathway is activated, and cells start growing. This phenomenon is recognized as the paradoxical effect of B-Raf Inhibitors. LUT014 harnesses the paradoxical effect of B-Raf Inhibitors in order to enhance cell proliferation and balance cell destruction, typical to radiation dermatitis.

Triumvira Immunologics Announces Publication Demonstrating the Safety and Efficacy of TAC T Cells Targeting Claudin 18.2 in Solid Tumors

On October 15, 2024 Triumvira Immunologics, a clinical-stage company developing novel, targeted autologous and allogeneic T cell therapeutics that co-opt the natural biology of T cells to treat patients with solid tumors, reported the publication of a peer-reviewed article titled "Preclinical development of T cells engineered to express a T cell antigen coupler (TAC) targeting Claudin 18.2-positive solid tumors" in Cancer Immunology Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Triumvira Immunologics, OCT 15, 2024, View Source [SID1234647212]). The article, authored by a team of scientists led by Dr. Andreas Bader, Triumvira’s Consulting Chief Scientific Officer, details the preclinical pharmacology and safety of TAC01-CLDN18.2, a novel autologous T cell therapy targeting Claudin 18.2 for the treatment of solid tumors. TAC01-CLDN18.2 is currently the subject of a clinical Phase I/II study (TACTIC-3, NCT05862324).

"Our findings highlight the unique advantages of TAC01-CLDN18.2, which is designed to target and eliminate tumors with high specificity while minimizing the risk of adverse events that are commonly associated with T cell and other therapies," said Andreas Bader, Ph.D., Consulting Chief Scientific Officer of Triumvira Immunologics. "This research underscores our commitment to developing next-generation T cell therapies that are both effective and safe, and we are excited to continue exploring the clinical potential of TAC01-CLDN18.2 in treating patients with Claudin 18.2 positive solid tumors."

"Publishing this research is a significant milestone for Triumvira, as it reinforces the potential of our TAC technology, currently in the clinic for Claudin 18.2 positive tumors, to transform the treatment landscape for cancer patients," said Robert Williamson, President of Triumvira Immunologics. "We remain committed to bringing innovative, life-saving treatments to patients in need, and this publication is a testament to the rigorous science in the company and dedication of our team."

The study highlights the novel and proprietary T cell Antigen Coupler (TAC) technology from Triumvira Immunologics, a chimeric receptor that promotes tumor antigen-specific activation of T cells by leveraging the natural T cell receptor complex without causing tonic signaling. The preclinical results demonstrate that CLDN18.2-TAC T cells exhibit specific and durable anti-tumor activity across various in vitro and in vivo models of gastric, gastroesophageal, and pancreatic cancers. Importantly, the study reports high selectivity as these T cells did not induce notable off-target or on-target/off-tumor toxicities in these preclinical models, suggesting its potential safety and efficacy in clinical settings.

Key Findings

Specificity and Activity: TAC01-CLDN18.2 T cells demonstrated high specificity and potent cytotoxicity against Claudin 18.2 positive tumor cells in both 2D cultures and 3D tumor spheroids, including models with low antigen expression.
CLDN18.2-TAC T vs CLDN18.2 CAR-T: In a head-to-head comparison against CLDN18.2-directed 2nd-generation CAR T cells, CLDN18.2-TAC T cells exhibited greater proliferative capacity, lower levels and delayed onset of T cell exhaustion, and overall greater and longer-lasting cytotoxicity in a recursive tumor cell killing assay.
In Vivo Efficacy: In mouse models of gastric, gastroesophageal, and pancreatic cancers, TAC01-CLDN18.2 T cells effectively eradicated tumor xenografts, with durable efficacy observed in recursive killing and tumor rechallenge experiments.
Safety Profile: The preclinical data showed that TAC01-CLDN18.2 T cells did not induce notable off-target or on-target/off-tumor toxicities, as these cells were unreactive to human cells representing vital organs.
Durable Response: The research indicates that TAC01-CLDN18.2 T cells can induce a long-lasting anti-tumor response, supporting their potential as a safe and effective treatment for patients with Claudin 18.2 positive solid tumors.
Full Publication Details

Title: Preclinical development of T cells engineered to express a T cell antigen coupler (TAC) targeting Claudin 18.2-positive solid tumors
Journal: Cancer Immunology Research
Corresponding Authors: Andreas Bader, Ph.D., Christopher Helsen, Ph.D.
Full Author List: Stacey Xu, Ling Wang, Philbert Ip, Ritu Randhawa, Tania Benatar, Suzanna Prosser, Prabha Lal, Alima Khan, Thanyashanthi Nitya-Nootan, Gargi Thakor, Heather MacGregor, Danielle Hayes, Andrea Vucicevic, Princy Mathew, Sadhak Sengupta, Christopher Helsen, and Andreas Bader

Jazz Pharmaceuticals Announces Statistically Significant Overall Survival and Progression-Free Survival Results for Zepzelca® (lurbinectedin) and Atezolizumab Combination in First-Line Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer

On October 15, 2024 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported positive top-line results from the Phase 3 clinical trial evaluating Zepzelca (lurbinectedin) in combination with the PD-L1 inhibitor atezolizumab (Tecentriq) compared to atezolizumab alone when administered as a maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC) following induction therapy with carboplatin, etoposide and atezolizumab (Press release, Jazz Pharmaceuticals, OCT 15, 2024, View Source [SID1234647211]). The combination of Zepzelca and atezolizumab demonstrated a statistically significant improvement in the primary endpoints of overall survival (OS) and progression-free survival (PFS), as assessed by an independent review facility (IRF), compared to treatment with atezolizumab alone.

"Each year, approximately 30,000 new cases of small cell lung cancer (SCLC) are reported in the U.S. A majority of these patients are diagnosed with extensive stage disease, which is aggressive and often difficult to treat, with poor prognosis,i,ii,iii" said Luis Paz-Ares, M.D., Ph.D., head of medical oncology at the Hospital Universitario 12 de Octubre in Madrid, Spain, and IMforte trial principal investigator. "These trial results demonstrate the efficacy of lurbinectedin, the most widely used agent in second-line SCLC in the United States, in combination with standard-of-care atezolizumab for patients in first-line maintenance treatment, a much-needed advancement for patients with extensive disease."

"The results of the Phase 3 IMforte trial are highly encouraging and showed a statistically significant benefit for the Zepzelca and atezolizumab combination for extensive-stage small cell lung cancer patients receiving this treatment in the first-line maintenance setting. These results demonstrate the potential of this regimen to delay disease progression and extend survival for patients with this aggressive disease," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "We are pleased with these clinically meaningful results and plan to submit an sNDA in the first half of 2025 to support this combination in the first-line maintenance setting. We thank the investigators and patients who are involved in this trial, along with our partners at Roche."

The combination was generally well-tolerated. The preliminary safety data in the ongoing trial was consistent with the known safety profiles of Zepzelca and atezolizumab with no new safety signals observed in the combination arm.

Jazz and Roche plan to submit these data for presentation at a future medical meeting.

About the IMforte Phase 3 Trial
IMforte (NCT05091567) is an ongoing Phase 3, randomized, multicenter maintenance trial evaluating the efficacy, safety and pharmacokinetics of Zepzelca plus atezolizumab, compared with standard-of-care first-line maintenance with atezolizumab alone, in adults (≥18 years) with ES-SCLC, following induction therapy with carboplatin, etoposide and atezolizumab. The primary endpoints for this study are OS and IRF-assessed PFS.

The trial consists of two phases: an induction phase and a maintenance phase. Participants were required to have an ongoing response or stable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 after the induction phase of four cycles of carboplatin, etoposide, and atezolizumab to be considered for eligibility screening for the maintenance phase. Eligible participants were randomized in a 1:1 ratio to receive either lurbinectedin plus atezolizumab or atezolizumab in the maintenance phase.

The trial is sponsored by Roche and co-funded by Jazz Pharmaceuticals. Additional information about the trial, including eligibility criteria and a list of clinical trial sites, can be found at: View Source (ClinicalTrials.gov Identifier: NCT05091567).

About Small Cell Lung Cancer
In the U.S., approximately 13 percent of lung cancers are small cell.ii Approximately 30,000 new cases of small cell lung cancer (SCLC) are reported in the U.S. each year.ii,iii The risk for developing SCLC is much higher among current or former tobacco smokers; however, SCLC can also be caused by exposure to secondhand smoke, asbestos, some inhaled chemicals, radiation and air pollution. People with a family history of lung cancer may also be at a higher risk, too.iv SCLC is the most aggressive form of lung cancer and it tends to spread quickly to other parts of the body including the brain, liver and bone.v,vi A large percentage of SCLC patients on treatment briefly achieve a response, although the cancer often returns and is usually more aggressive and resistant to regimens that were previously effective.ii

About Zepzelca (lurbinectedin)
Zepzelca is an alkylating drug that binds guanine residues within DNA. This triggers a cascade of events that can affect the activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in disruption of the cell cycle and eventual cell death.iv

The FDA approved Zepzelca under accelerated approval in June 2020 for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy. The approval is based on overall response rate (ORR) and duration of response demonstrated in an open-label, monotherapy clinical study. In December 2021, Jazz and PharmaMar announced the initiation of LAGOON, a confirmatory Phase 3 clinical trial of Zepzelca for the treatment of patients with relapsed small cell lung cancer. If positive, LAGOON could confirm the benefit of Zepzelca in the treatment of small cell lung cancer (SCLC) when patients progress following 1L treatment with a platinum-based regimen and support full approval in the U.S.

Zepzelca is a prescription medicine used to treat adults with SCLC that has spread to other parts of the body (metastatic) and who have received treatment with chemotherapy that contains platinum, and it did not work or is no longer working. Zepzelca is approved based on response rate and how long the response lasted.

Important Safety Information for ZEPZELCA

Before receiving ZEPZELCA, tell your healthcare provider about all of your medical conditions, including if you:

have liver or kidney problems.
are pregnant or plan to become pregnant. ZEPZELCA can harm your unborn baby.
Females who are able to become pregnant:

Your healthcare provider should do a pregnancy test before you start treatment with ZEPZELCA.
You should use effective birth control (contraception) during treatment with and for 6 months after your last dose of ZEPZELCA.
Tell your healthcare provider right away if you become pregnant or think that you are pregnant during treatment with ZEPZELCA.
Males with female partners who are able to become pregnant should use effective birth control during treatment with and for 4 months after their last dose of ZEPZELCA.

are breastfeeding or plan to breastfeed. It is not known if ZEPZELCA passes into your breastmilk. Do not breastfeed during treatment with ZEPZELCA and for 2 weeks after your last dose of ZEPZELCA. Talk to your healthcare provider about the best way to feed your baby during treatment with ZEPZELCA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain other medicines may affect how ZEPZELCA works.
What should I avoid while using ZEPZELCA?
Avoid eating or drinking grapefruit, Seville oranges, or products that contain grapefruit juice and Seville oranges during treatment with ZEPZELCA.
ZEPZELCA can cause serious side effects, including:

Low blood cell counts. Low blood counts including low neutrophil counts (neutropenia) and low platelet counts (thrombocytopenia) are common with ZEPZELCA, and can also be severe. Some people with low white blood cell counts may get fever, or an infection throughout the body (sepsis), that can cause death. Your healthcare provider should do blood tests before you receive each treatment with ZEPZELCA to check your blood cell counts.
Tell your healthcare provider right away if you develop:
fever or any other signs of infection
unusual bruising or bleeding
tiredness
pale colored skin
Liver problems. Increased liver function tests are common with ZEPZELCA and can also be severe. Your healthcare provider should do blood tests to check your liver function before you start and during treatment with ZEPZELCA.
Tell your healthcare provider right away if you develop symptoms of liver problems including:
loss of appetite
nausea or vomiting
pain on the right side of your stomach area (abdomen)
Leakage of ZEPZELCA out of your vein during the infusion. If ZEPZELCA leaks into the tissues around your infusion site, it can cause damage and death of tissue cells around the infusion site. You may need to have surgery to remove any dead tissue. Tell your healthcare provider right away if you see any ZEPZELCA leaking out of your vein or around the catheter during your infusion, or if you notice any redness, swelling, itching or discomfort at the infusion site at any time.
Severe muscle problems (rhabdomyolysis). Tell your healthcare provider if you have severe muscle pain or weakness.
Your healthcare provider may temporarily stop treatment, lower your dose, or permanently stop ZEPZELCA if you develop serious side effects during treatment with ZEPZELCA.

The most common side effects of ZEPZELCA include:

tiredness
low white and red blood cell counts
increased kidney function blood test (creatinine)
increased liver function blood tests
increased blood sugar (glucose)
nausea
decreased appetite
muscle and joint (musculoskeletal) pain
low level of albumin in the blood
constipation
trouble breathing
low levels of sodium and magnesium in the blood
vomiting
cough
diarrhea
These are not all of the possible side effects of ZEPZELCA.

Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Jazz Pharmaceuticals at 1-800-520-5568.

Please see full Prescribing Information including Patient Information, and discuss with your doctor.

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 medicine used to treat:

Adults with a type of lung cancer called small cell lung cancer (SCLC). Atezolizumab may be used with the chemotherapy medicines carboplatin and etoposide as your first treatment when your lung cancer:

is a type called "extensive-stage small cell lung cancer," which means that it has spread or grown.
It is not known if atezolizumab is safe and effective when used in children for the treatment of SCLC.

Important Safety Information

What is the most important information about atezolizumab?
Atezolizumab can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during your treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any new or worse signs or symptoms, including:

Lung problems

cough
shortness of breath
chest pain
Intestinal problems

diarrhea (loose stools) or more frequent bowel movements than usual
stools that are black, tarry, sticky, or have blood or mucus
severe stomach-area (abdomen) pain or tenderness
Liver problems

yellowing of your skin or the whites of your eyes
severe nausea or vomiting
pain on the right side of your stomach area (abdomen)
dark urine (tea colored)
bleeding or bruising more easily than normal
Hormone gland problems

headaches that will not go away or unusual headaches
eye sensitivity to light
eye problems
rapid heartbeat
increased sweating
extreme tiredness
weight gain or weight loss
feeling more hungry or thirsty than usual
urinating more often than usual
hair loss
feeling cold
constipation
your voice gets deeper
dizziness or fainting
changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems

decrease in your amount of urine
blood in your urine
swelling of your ankles
loss of appetite
Skin problems

rash
itching
skin blistering or peeling
painful sores or ulcers in mouth or nose, throat, or genital area
fever or flu-like symptoms
swollen lymph nodes
Problems can also happen in other organs.
These are not all of the signs and symptoms of immune system problems that can happen with atezolizumab. Call or see your healthcare provider right away for any new or worse signs or symptoms, including:

Chest pain, irregular heartbeat, shortness of breath, or swelling of ankles
Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
Persistent or severe muscle pain or weakness, muscle cramps
Low red blood cells, bruising
Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:

chills or shaking
itching or rash
flushing
shortness of breath or wheezing
dizziness
feeling like passing out
fever
back or neck pain
Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with atezolizumab. Your healthcare provider will monitor you for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with atezolizumab. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with atezolizumab if you have severe side effects.

Before you receive atezolizumab, tell your healthcare provider about all of your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to your chest area
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. Atezolizumab can harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with atezolizumab. Females who are able to become pregnant:
Your healthcare provider should do a pregnancy test before you start treatment with atezolizumab.
You should use an effective method of birth control during your treatment and for at least 5 months after the last dose of atezolizumab.
are breastfeeding or plan to breastfeed. It is not known if atezolizumab passes into your breast milk. Do not breastfeed during treatment and for at least 5 months after the last dose of atezolizumab.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of atezolizumab when used in lung cancer with other anti-cancer medicines include:

feeling tired or weak
nausea
hair loss
constipation
diarrhea
decreased appetite
Atezolizumab may cause fertility problems in females, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of atezolizumab. Ask your healthcare provider or pharmacist for more information about the benefits and side effects of atezolizumab.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.