Sacituzumab Tirumotecan vs Standard Therapy for Lung Cancer
Recruiting in Palo Alto (17 mi)
+127 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Merck Sharp & Dohme LLC
Must not be taking: Immunosuppressants, Corticosteroids, Live vaccines, others
Disqualifiers: Squamous NSCLC, Cardiovascular disease, Pneumonitis, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate sacituzumab tirumotecan versus pemetrexed in combination with carboplatin for the treatment of epidermal growth factor receptor (EGFR)-mutated advanced non-squamous non-small cell lung cancer (NSCLC). Participants in this study have NSCLC that has continued to progress on prior treatment with EGFR tyrosine kinase inhibitors (TKIs).
The primary hypotheses of this study are that sacituzumab tirumotecan is better than platinum-based doublet chemotherapy (pemetrexed and carboplatin) in regard to progression-free survival (PFS) and overall survival (OS).
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must have recovered from adverse effects of previous cancer treatments and cannot have active infections requiring systemic therapy.
What data supports the effectiveness of the drug Sacituzumab Tirumotecan for lung cancer?
Carboplatin, a component of the treatment, has shown favorable survival rates in patients with advanced non-small-cell lung cancer (NSCLC) compared to its parent analogue cisplatin. Additionally, pemetrexed, another component, has been effective in treating relapsed NSCLC with similar response and survival outcomes to other treatments, but with less toxicity.
12345Is Sacituzumab Tirumotecan safe for humans?
Pemetrexed, a component of the treatment, has been used safely in combination with other drugs for lung cancer and mesothelioma, but it can cause side effects like low blood cell counts, fatigue, and nausea. Carboplatin, another component, is generally safe but can also cause low blood cell counts and other side effects. Always consult with a healthcare provider for personalized advice.
678910What makes the drug Sacituzumab Tirumotecan unique for lung cancer treatment?
Sacituzumab Tirumotecan is unique because it combines a targeted therapy approach with traditional chemotherapy, potentially offering a novel mechanism of action by delivering a potent chemotherapy agent directly to cancer cells, which may improve effectiveness and reduce side effects compared to standard therapies.
13111213Eligibility Criteria
This trial is for adults with advanced-stage nonsquamous NSCLC that has worsened despite EGFR tyrosine kinase inhibitors. Candidates must have a life expectancy of at least 3 months, controlled HIV or Hepatitis B/C if present, and recovered from previous cancer therapy side effects.Inclusion Criteria
My lung cancer is advanced and not squamous cell type.
My HIV is well controlled with medication.
I am HBsAg positive but have been on HBV therapy for 4 weeks with an undetectable viral load.
+3 more
Exclusion Criteria
I am HIV-positive with a history of Kaposi's sarcoma or Castleman's Disease.
I am currently on medication for an infection.
I have not received a live vaccine within the last 30 days.
+13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either sacituzumab tirumotecan or pemetrexed plus carboplatin until discontinuation criteria are met
Up to approximately 51 months
Every 2-3 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to approximately 51 months
Participant Groups
The study compares sacituzumab tirumotecan to the combination of pemetrexed and carboplatin in treating advanced non-squamous NSCLC with EGFR mutations. It aims to see which treatment leads to longer survival without disease progression.
2Treatment groups
Experimental Treatment
Active Control
Group I: Sacituzumab tirumotecanExperimental Treatment6 Interventions
Participants receive 4 mg/kg sacituzumab tirumotecan via intravenous (IV) infusion every 2 weeks (Days 1, 15, and 29 of every 6-week cycle) until discontinuation criteria is met.
Group II: Pemetrexed Plus CarboplatinActive Control2 Interventions
Participants receive, via IV infusion, 500 mg/m2 pemetrexed every 3 weeks (Days 1 and 22 of every 6-week cycle) plus area under the curve (AUC) 5 mg/mL\*min carboplatin every 3 weeks (Days 1 and 22 of every 6-week cycle for 4 doses), then 500 mg/m2 pemetrexed every 3 weeks until discontinuation criteria is met.
Carboplatin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
🇪🇺 Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
McGill University Health Centre ( Site 0204)Montréal, Canada
Astera Cancer Care ( Site 0032)East Brunswick, NJ
Millennium Research & Clinical Development ( Site 0035)Houston, TX
Mid Florida Hematology and Oncology Center ( Site 0005)Orange City, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Merck Sharp & Dohme LLCLead Sponsor
References
Chemotherapy in metastatic non-small-cell lung cancer. [2022]Over the last decade, a group of new agents with differing mechanisms of action have shown great promise in early clinical studies in non-small-cell lung cancer (NSCLC). These include the taxanes docetaxel (Taxotere) and paclitaxel (Taxol); the nucleoside analog gemcitabine (Gemzar); the vinca alkaloid vinorelbine (Navelbine); the topoisomerase-I inhibitor irinotecan (Camptosar, CPT-11); and the bioreductive agent tirapazamine. Cisplatin (Platinol), which has been the "backbone" of combination chemotherapy in patients with NSCLC because of its proven single-agent activity, has been examined in combination with these agents as well as radiation and surgery in numerous trials. This article summarizes trials of these combination therapies in the treatment of NSCLC.
Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. [2015]Chemotherapeutic intervention in advanced and metastatic non-small-cell lung cancer (NSCLC) has changed over the past 2 decades. The improvements offered by cisplatin (Platinol)-based regimens, though significant in terms of survival and quality of life, were modest at best. Carboplatin (Paraplatin), which possesses a toxicity profile favorable to that of its parent analogue cisplatin, yielded survival rates superior to that of the cisplatin-combination chemotherapy arms in a large randomized study of patients with metastatic non-small-cell lung cancer. With the introduction of taxanes in the early 1990s, paclitaxel (Taxol) demonstrated single-agent activity of 21% to 24%, with a 40% 1-year survival rate in metastatic disease. The next generation of phase I/II studies evaluated the efficacy of paclitaxel in combination with carboplatin. Results with this regimen have shown substantial promise, and 1-year survival rates as high as 54% have been reported. Full doses of both agents have been combined without any additional toxicity, and there appears to be a dose-response effect with paclitaxel. The combination of paclitaxel and carboplatin has been incorporated as the investigational arm of all the ongoing multicenter and cooperative group studies. While the results from these randomized studies are awaited, this combination has become the most widely used regimen in community practice for patients with non-small-cell lung cancer. It is also being evaluated for treatment at earlier disease stages, in the setting of minimal tumor burden, and in combined-modality regimens.
Future directions in non-small-cell lung cancer: a continuing perspective. [2005]Non-small-cell lung cancer (NSCLC) will increasingly come under better control as the current approaches to therapy are more broadly employed and as new therapies are deployed against recently elucidated molecular pathways. In the United States, real progress is finally being made in decreasing tobacco consumption and in lung cancer incidence. The traditional chemotherapeutic compounds that became available earlier this decade (paclitaxel [Taxol], docetaxel [Taxotere], gemcitabine [Gemzar], vinorelbine [Navelbine], irinotecan [Camptosar], topotecan [Hycamtin], and edatrexate) have all been tested as single agents and as doublets with cisplatin (Platinol) and carboplatin (Paraplatin). Paclitaxel with cisplatin or carboplatin and vinorelbine, docetaxel, or gemcitabine with cisplatin have all demonstrated significant activity that now appears clearly better than the prior standard therapy of etoposide (VePesid)/cisplatin. Phase III studies sorting out their benefit relative to each other should be completed in the next 1 to 2 years. To date, no triplet therapy appears better than the corresponding doublet. Non-platinum-containing doublets are just completing their first round of assessments. Aside from new drugs and applications, the use of "small" molecules to inhibit either signal transduction pathways or gene activation is likely to accelerate. Most of the newer chemotherapeutic agents can be interdigitated with radiation and surgery, although evaluations into sequence and dose issues continue. The superior outcomes seen with the newer regimens should translate to the adjuvant and preoperative or preradiotherapy settings relatively quickly. It is now clear that NSCLC is as responsive to therapy as small-cell lung cancer (SCLC) and that outcomes are superior for NSCLC. The enthusiasm for treating SCLC displayed by nononcologists and nonthoracic medical oncologists should be shared for NSCLC.
Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. [2022]PURPOSE To evaluate the efficacy of cetuximab plus taxane/carboplatin (TC) as first-line treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS This multicenter, open-label, phase III study enrolled 676 chemotherapy-naïve patients with stage IIIB (pleural effusion) or IV NSCLC, without restrictions by histology or epidermal growth factor receptor expression. Patients were randomly assigned to cetuximab/TC or TC. TC consisted of paclitaxel (225 mg/m(2)) or docetaxel (75 mg/m(2)), at the investigator's discretion, and carboplatin (area under the curve = 6) on day 1 every 3 weeks for
Role of pemetrexed in non-small cell lung cancer. [2022]Pemetrexed was approved for the treatment of relapsed or chemotherapy refractory non-small cell lung cancer patients, as it produced similar response and survival outcomes and less toxicity as compared to taxotere. Pemetrexed in combination with platinum analogs or with gemcitabine or vinorelbine, produce equivalent responses and overall survival results compared to combinations of platinum analogs with other drugs. The role of bevacizumab and the inhibitors of epithelial growth factor receptor also should be evaluated in selected patients with NSCLC treated with pemetrexed combinations. Further increases in drug dose may be possible using transfer of drug resistance genes in hematopoietic stem cells.
FDA drug approval summaries: pemetrexed (Alimta). [2022]The purpose of this report is to summarize information on pemetrexed (LY231514; MTA; Alimta; Eli Lilly and Company; Indianapolis, IN), a drug recently approved by the U.S. Food and Drug Administration (FDA). The review of the efficacy and safety of pemetrexed is summarized below. Pemetrexed is a pyrrolopyrimidine antifolate. It inhibits thymidylate synthase, glycinamide ribonucleotide formyltransferase, and dihydrofolate reductase. In a single, randomized, single-blind, multicenter phase III trial, the efficacy and safety of pemetrexed combined with cisplatin (Platinol; Bristol-Myers Squibb; Princeton, NJ) were compared with those of single-agent cisplatin in 448 patients with malignant pleural mesothelioma. Two hundred twenty-six patients were randomized to receive pemetrexed and cisplatin, while 222 patients were randomized to receive cisplatin alone. The primary study end point was survival. Median survival times were 12.1 months for the pemetrexed plus cisplatin treated arm and 9.3 months for the cisplatin alone arm. Pemetrexed causes myelosuppression. The most common adverse events were neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. On February 4, 2004, pemetrexed was approved by the FDA in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m(2) administered as an i.v. infusion over 10 minutes on day 1 of each 21-day cycle together with cisplatin at a dose of 75 mg/m(2) infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B(12) injections prior to the start of therapy and continue these during therapy to reduce severe toxicities. Patients should also receive corticosteroids with chemotherapy to reduce the risk of skin rashes. Approval was based on superior survival as a clinical benefit.
Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance in Japanese patients with non-squamous non-small cell lung cancer: A subgroup analysis of elderly patients. [2022]The combination of pemetrexed and carboplatin is commonly used for the treatment of advanced non-squamous non-small cell lung cancer (NSCLC), mainly because it is comparatively effective and less toxic than other platinum-doublet therapies. Using the JMII (JACAL) study, we report the efficacy and safety of this treatment followed by pemetrexed maintenance in the elderly population (≥70 years of age).
Pemetrexed and carboplatin, an active option in first-line treatment of elderly patients with advanced non-small cell lung cancer (NSCLC): a phase II trial. [2015]The synergistic activity of pemetrexed with platinum agents in non-small cell lung cancer (NSCLC) and the renal safety of carboplatin suggest a balanced benefit/risk profile for this combination in elderly patients. This multicenter, single-arm, phase II study included 62 patients (≥70 years) with chemonaïve advanced NSCLC, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, and assigned to receive 6 cycles of 3-weekly pemetrexed 500 mg/m(2) and carboplatin AUC 5. The primary endpoint was objective tumor response rate (ORR). Sixty-two patients received at least one dose of chemotherapy. Median age was 76.4 years [70.2-86] and all patients had PS 0 (16.1%) or PS 1 (83.9%). Stage IIIb disease in 21% patients and stage IV in 79% patients. Non-squamous cell carcinoma in 66.1% patients (adenocarcinoma 51.6%, large cell carcinoma 8.1%, other 6.5%) and squamous cell carcinoma in 33.9% patients. ORR was 28.6% (95% confidence interval [CI], 16.58-43.26), all were partial responses. Stable disease rate was 42.9%. Grade 3/4 toxicities related to study drugs were: asthenia 16.1%, anorexia 4.8%, diarrhea 3.2%, neutropenia 51.6%, leucopenia 30.7%, thrombocytopenia 29%, anemia 19.4%. One related fatal septic shock occurred. In advanced NSCLC, pemetrexed use is restricted to non-squamous histology. The combination pemetrexed-carboplatin could be a valuable treatment option in elderly patients. Neutropenia was the most common toxicity. The ORR is within the range of data reported for pemetrexed-carboplatin in the general NSCLC population (24-31%).
Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. [2015]Pemetrexed in combination with cisplatin (Pem/Cis) is the only approved chemotherapeutic regimen for malignant pleural mesothelioma (MPM). At the time of launch, limited safety information was available. The purpose of this postmarketing all-case registry study was to investigate the safety and effectiveness of pemetrexed in patients with MPM.
Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. [2015]Pemetrexed has established efficacy, and is the backbone for chemotherapy in patients with malignant pleural mesothelioma (MPM). An International Expanded Access Program provided >3000 mesothelioma patients with access to single-agent pemetrexed or pemetrexed plus platinum analogs (cisplatin or carboplatin) in 13 countries. In this article, we report the safety and efficacy data of MPM patients who were treated with single-agent pemetrexed (n = 812).
Phase II study of nedaplatin and irinotecan as adjuvant chemotherapy for completely resected non-small cell lung cancer. [2019]Cisplatin-based chemotherapy is the standard adjuvant therapy for patients with completely resected stage II or III non-small cell lung cancer (NSCLC). However, the completion rate of four cycles of cisplatin-based chemotherapy is about 50%. This phase II study was conducted to evaluate the tolerability and efficacy of nedaplatin and irinotecan as adjuvant chemotherapy.
Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial. [2013]This phase III study compared efficacy and safety of topotecan-cisplatin (TP) versus topotecan-etoposide (TE) versus cisplatin-etoposide (PE) in chemo-naïve extensive disease small-cell lung cancer patients.
Lung cancer. [2007]The results of the many clinical trials published in 1997 had only modest impact on the treatment results using either cytostatic agents alone or combined with radiotherapy in lung cancer. In SCLC, combination chemotherapy including platin-compounds (cisplatin, carboplatin) and the podophyllotoxins (etoposide and teniposide) continue to be the cornerstone of therapy. Complete plus partial responses to combination chemotherapy occurs in 80-90% of all patients. Median survival is at present 11-17 months, and overall 5-year survival approximately 5% depending on the initial tumor stage. The duration of treatment has been shortened to 5-6 months. In relapsing patients topotecan and paclitaxel appear to have clinical useful activity. For epidermoid, adeno- and large cell carcinoma further support has arisen for the use of preoperative and preirradiatory chemotherapy in stage III NSCLC, but further studies are needed before specific recommendations can be given for general use. For patients with advanced NSCLC, new innovative treatments are still urgently needed. Platin-containing regimens with the inclusion of new agents, such as gemcitabine, taxenes, and navelbine, yielded response rates of 42-55% in phase II trials, but results from large phase III trials are necessary in order to measure the impact of these new agents in the management of NSCLC. Major improvements of therapy for mesothelioma have not occurred within the last year.