MK-2870 for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+192 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Merck Sharp & Dohme LLC
Must be taking: EGFR TKIs
Must not be taking: Immunosuppressants, Corticosteroids
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 chemotherapy (docetaxel or pemetrexed) for the treatment of previously-treated non-small cell lung cancer (NSCLC) with exon 19del or exon 21 L858R EGFR mutations (hereafter referred to as EGFR mutations or EGFR-mutated) or any of the follow genomic alterations: ALK gene rearrangements, ROS1 rearrangements, BRAF V600E mutations, NTRK gene fusions, MET exon 14 skipping mutations, RET rearrangements, or less common EGFR point mutations of exon 20 S768I, exon 21 L861Q, or exon 18 G719X mutations. The primary hypotheses are that sacituzumab tirumotecan is: (1) superior to chemotherapy with respect to progression-free survival (PFS) per RECIST 1.1 as assessed by BICR in NSCLC with EGFR mutations; and (2) superior to chemotherapy with respect to overall survival (OS) in NSCLC with EGFR mutations.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot have received any systemic anticancer therapy, including investigational agents, within 4 weeks before joining the study.
What data supports the effectiveness of the drug MK-2870 for treating non-small cell lung cancer?
Research shows that docetaxel and pemetrexed, which are part of the treatment, have been used effectively in treating non-small cell lung cancer. Docetaxel has shown a survival benefit in various cancer settings, and pemetrexed has been approved for use in non-small cell lung cancer with a favorable safety profile.
12345What safety data exists for MK-2870 and related treatments in humans?
Docetaxel and pemetrexed, which are related to MK-2870, have been studied for safety in treating non-small cell lung cancer. Pemetrexed is considered to have a more favorable safety profile than docetaxel, causing fewer issues like low white blood cell counts and related infections.
24567What makes the drug MK-2870 unique for treating non-small cell lung cancer?
The drug MK-2870, when combined with docetaxel and pemetrexed, offers a novel approach by potentially enhancing the effectiveness of existing chemotherapy agents like docetaxel and pemetrexed, which have shown significant activity against non-small cell lung cancer. This combination may provide a new option for patients who have progressed on or after standard treatments.
89101112Eligibility Criteria
This trial is for adults with advanced or metastatic non-squamous NSCLC who have specific mutations and have already tried some treatments. They should be relatively healthy (ECOG status of 0 or 1), not have certain infections, and must not have had recent vaccinations or other cancer treatments within the last month.Inclusion Criteria
My advanced lung cancer is non-squamous and has specific mutations.
My cancer has grown despite treatment, as shown by scans.
I've had specific lung cancer treatments, including a targeted therapy for a certain mutation.
+6 more
Exclusion Criteria
Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
I experience significant numbness or pain in my hands or feet.
I have severe dry eye, eyelid inflammation, or corneal disease.
+17 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive sacituzumab tirumotecan or chemotherapy (docetaxel or pemetrexed) in 6-week cycles
Up to approximately 41 months
IV infusions on Days 1, 15, and 29 for sacituzumab tirumotecan; Days 1 and 22 for chemotherapy
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to approximately 6 years
Participant Groups
The study tests MK-2870 against standard chemotherapy drugs (docetaxel or pemetrexed) in patients with certain genetic changes in their lung cancer. The goal is to see if MK-2870 can improve survival without the disease getting worse compared to chemotherapy.
2Treatment groups
Experimental Treatment
Active Control
Group I: Sacituzumab tirumotecanExperimental Treatment1 Intervention
Participants will receive 4 mg/kg of sacituzumab tirumotecan via intravenous (IV) infusion on Days 1, 15 and 29 of each 6-week cycle. Additionally, participants receive diphenhydramine (or equivalent), an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to the first 4 infusions of sacituzumab tirumotecan. At subsequent infusions, the H2 antagonist and dexamethasone are optional, at the discretion of the investigator.
Group II: ChemotherapyActive Control2 Interventions
Participants will receive 75 mg/m\^2 of docetaxel or 500 mg/m\^2 of pemetrexed by IV infusion on Days 1 and 22 of every 6-week cycle.
Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
🇪🇺 Approved in European Union as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
🇨🇦 Approved in Canada as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
🇯🇵 Approved in Japan as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Princess Margaret Cancer Centre ( Site 0204)Toronto, Canada
Karmanos Cancer Institute ( Site 0018)Detroit, MI
University Of Nebraska Medical Center ( Site 0011)Omaha, NE
University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 0015)Cincinnati, OH
More Trial Locations
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Who Is Running the Clinical Trial?
Merck Sharp & Dohme LLCLead Sponsor
References
Randomized Phase III Study of Docetaxel Plus Cisplatin Versus Pemetrexed Plus Cisplatin as First-line Treatment of Nonsquamous Non-Small-cell Lung Cancer: A TRAIL Trial. [2018]To date, no prospective phase III trials have directly compared the efficacy of pemetrexed plus cisplatin (Pem-Cis) with docetaxel plus cisplatin (Doc-Cis) in patients with nonsquamous non-small-cell lung cancer.
[Efficacy and safety of docetaxol, pemetrexed and EGFR-TKIs as second-line treatment for patients with advanced non-small-cell lung cancer]. [2018]To compare the efficacy and safety of docetaxol, pemetrexed and EGFR-TKIs in the second-line treatment for patients with advanced non-small cell lung cancer.
The current status of docetaxel in solid tumors. An M. D. Anderson Cancer Center Review. [2018]In less than a decade, docetaxel (Taxotere) has progressed from initial studies in anthracycline-refractory metastatic breast cancer to several large, phase III randomized trials evaluating its efficacy as adjuvant, neoadjuvant, and first-line therapy for metastatic breast cancer, non-small-cell lung cancer (NSCLC), and ovarian cancer. In other tumor types, including prostate, head and neck, gastric, and bladder cancer, ongoing phase III trials are comparing docetaxel-containing regimens to previously established regimens. For the seven tumor types reviewed in this supplement, phase III study information for docetaxel or docetaxel-based combinations are presented. Impressive results have been consistently demonstrated in the trials reported to date. In early-stage and metastatic breast cancer, NSCLC, and ovarian cancer, randomized trials have shown that docetaxel-containing therapies are superior to or as effective as established standard chemotherapeutic regimens and are often associated with an improved safety profile. Trials of docetaxel as adjuvant and neoadjuvant therapy for breast cancer are under way or have been completed. Docetaxel has demonstrated a survival benefit in many settings that previously had not achieved such a benefit. For example, a survival benefit was demonstrated in anthracycline-resistant breast cancer and second-line NSCLC cancer phase III comparative trials.
FDA drug approval summary: pemetrexed for injection (Alimta) for the treatment of non-small cell lung cancer. [2022]On August 19, 2004, pemetrexed for injection (Alimta); Eli Lilly and Company, Indianapolis, IN, http://www.lilly.com) received accelerated approval as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had received prior chemotherapy. Approval was primarily based on a single, controlled, unblinded trial. Five hundred seventy-one protocol-eligible patients were randomized to receive either pemetrexed or docetaxel (Taxotere); Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharmaus.com). The primary efficacy end point was overall survival. The median survival times were 8.3 months in the pemetrexed arm and 7.9 months in the docetaxel arm. Neither superiority nor noninferiority for overall survival could be demonstrated, the latter because a reliable and consistent survival effect of docetaxel could not be estimated and because of significant crossover of pemetrexed-treated patients to docetaxel after tumor progression. Comparable response rates, 9.1% for pemetrexed and 8.8% for docetaxel, times to progressive disease, and progression-free survival times supported the conclusion that an effect of pemetrexed on survival was reasonably likely, however. In addition, pemetrexed was felt to have a more favorable safety profile than docetaxel. Of greatest importance, pemetrexed caused significantly less neutropenia, febrile neutropenia, neutropenic infections, and need for granulocyte/macrophage colony-stimulating factors.
Comparison of pemetrexed and docetaxel as salvage chemotherapy for the treatment for nonsmall-cell lung cancer after the failure of epidermal growth factor receptor-tyrosine kinase inhibitors. [2022]To compare the therapeutic effects and adverse reactions of pemetrexed and docetaxel as salvage chemotherapy in patients with nonsmall-cell lung cancer (NSCLC) after the failure of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI).
Phase II study of docetaxel for advanced or metastatic platinum-refractory non-small-cell lung cancer. [2018]We conducted a phase II study to determine the response to and toxicity of docetaxel (Taxotere; Rhône-Poulenc Rorer Pharmaceuticals, Inc, Collegeville, PA) in patients with advanced non-small-cell lung cancer refractory to prior platinum-containing chemotherapy (PCC) regimens.
Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer. [2018]We conducted a phase II study to determine the response and toxicity of docetaxel (Taxotere; Rhône-Poulenc Rorer Pharmaceuticals, Inc, Collegeville, PA) in chemotherapy-naive patients with advanced non-small-cell lung cancer.
Second-line chemotherapy for non-small cell lung cancer. [2022]Several agents have been evaluated for the second-line treatment of patients with non-small cell lung cancer. The TAX 317 trial found that patients treated with docetaxel (Taxotere) 75 mg/m2 had significantly longer survival than those treated with best supportive care alone. In addition, symptom control was better for patients who received chemotherapy. The TAX 320 trial found that treatment with docetaxel 75 or 100 mg/m2 resulted in significantly higher response rates than treatment with vinorelbine (Navelbine) or ifosfamide (Mitoxana), and the 1-year survival rate was also significantly better for patients treated with docetaxel 75 mg/m2. A large randomized trial compared pemetrexed (LY-231514 or Alimta) 500 mg/m2 with docetaxel 75 mg/m2. Response and survival rates were similar in the two treatment arms, however, the toxicity profile of pemetrexed was superior to that of docetaxel with significantly less Grade 3/4 neutropenia and febrile neutropenia. Fewer patients in the pemetrexed arm required hospitalization. Topotecan (Hycamtin) 2.3 mg/m2/day orally for 5 days has been compared with docetaxel 75 mg/m2 in a large 800-patient study. The results of this trial are awaited. Gemcitabine (Gemzar) and irinotecan (Campto) have been evaluated both as single agents and in combination with each other and study results do not suggest that either of these drugs is superior to docetaxel or pemetrexed. The vinca alkaloid vinorelbine has proved to be inferior to docetaxel in a randomized trial. The epidermal growth factor receptor inhibitors gefitinib (ZD1839, Iressa) and erlotinib (CP-358774, OSI 774, Tarceva) have been evaluated in Phase II trials in the second- and third-line setting. Both drugs have demonstrated interesting response rates ranging from 10 to almost 20%. The results of placebo-controlled randomized trials of this family of drugs are awaited. In summary, several studies have now found a definite role for the second-line treatment of patients with non-small cell lung cancer.
Summary of phase II data of docetaxel (Taxotere), an active agent in the first- and second-line treatment of advanced non-small cell lung cancer. [2018]Six phase II studies have been conducted in the United States and Europe using docetaxel (Taxotere; Rhone-Poulenc Rorer, Antony, France) for advanced non-small cell lung cancer. One hundred eighty chemotherapy-naive patients in four studies and 88 patients who failed prior platinum-containing chemotherapy in two studies were treated with docetaxel 75 to 100 mg/m2 intravenously over 1 hour every 3 weeks. Fifty-nine percent of patients had adenocarcinoma and 82% had stage IV disease. At a dose of 100 mg/m2, 30% of evaluable chemotherapy-naive patients (27% of the intent-to-treat population) and 20% of evaluable platinum-refractory/resistant patients (17% of the intent-to-treat population) achieved a partial response; projected median survival is 9 months in both studies. Neutropenia was the primary dose-limiting acute side effect. Fluid retention, which occurred in patients who received multiple courses of treatment, was common but rarely dose-limiting, and may be ameliorated with prophylactic corticosteroids. Other toxic effects were relatively mild. Docetaxel has significant activity against advanced non-small cell lung cancer, producing a major response in both chemotherapy-naive patients and patients who had failed prior platinum-containing chemotherapy.
Schedule-dependent synergism and antagonism between pemetrexed and docetaxel in human lung cancer cell lines in vitro. [2018]Pemetrexed and docetaxel show clinical activities against a variety of solid tumors including lung cancers. To identify the optimal schedule for combination, cytotoxic interactions between pemetrexed and docetaxel were studied at various schedules using three human lung cancer cell lines A-549, Lu-99, and SBC-5 in vitro.
Ramucirumab for the treatment of advanced or metastatic non-small cell lung cancer. [2023]On 12 December 2014, the U.S. Food and Drug Administration (FDA) approved ramucirumab for use in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Areas covered: This review discusses the best treatment strategy for ramucirumab, a vascular endothelial growth factor receptor-2 inhibitor for patients with advanced NSCLC. Expert opinion: The addition of ramucirumab to docetaxel in the treatment of patients with metastatic NSCLC who have progressed on or after platinum-based chemotherapy confers a 1.4-month improvement in overall survival, with an acceptable toxicity profile. The potential impact of the approval of the programmed death receptor-1 (PD-1)-blocking antibody nivolumab or pembrolizumab on the use of ramucirumab plus docetaxel in advanced NSCLC patient population is uncertain in clinical practice. In order to improve overall outcomes for patients with advanced NSCLC, both ramucirumab plus docetaxel and the PD-1-blocking antibody should be used in any treatment line.
Is there any impact of new drugs on the outcome of advanced NSCLC? An overview of the Southern Italy Cooperative Oncology Group trials. [2022]Lung cancer represents the major cause of cancer-related death in Europe and North America, accounting for 28% of all cancer deaths. Seventy to 80% of all lung cancers are non-small cell lung cancers (NSCLCs), and approximately 75 % of these patients present with locally advanced or disseminated disease. Even though chemotherapy is now recommended in the majority of cases of unresectable NSCLC, it still fails to substantially modify the fate of these patients. In recent years, several active cytotoxic drugs (paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan) have been developed, showing an overall response rate (ORR)