Dato-DXd + Pembrolizumab for Advanced Lung Cancer
(TROPION-Lung08 Trial)
Recruiting in Palo Alto (17 mi)
+238 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Daiichi Sankyo, Inc.
Must not be taking: Topoisomerase inhibitors, TROP2 therapies
Disqualifiers: Prior NSCLC treatment, CNS metastases, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab alone in participants with advanced or metastatic non-small cell lung cancer (NSCLC) of non-squamous histology.
Will I have to stop taking my current medications?
The trial requires an adequate treatment washout period (time without taking certain medications) before starting the study. However, the specific medications you need to stop are not detailed in the provided information.
What data supports the effectiveness of the drug combination Dato-DXd and Pembrolizumab for advanced lung cancer?
Research shows that pembrolizumab alone is a standard treatment for certain types of advanced lung cancer, but many patients do not experience long-term control. The combination of Dato-DXd and pembrolizumab has shown promising safety and antitumor activity in advanced lung cancer, suggesting it may be more effective than pembrolizumab alone.
12345Is the combination of Dato-DXd and Pembrolizumab safe for humans?
Pembrolizumab, one of the drugs in the combination, has been used in various cancer treatments and is generally safe, but it can cause side effects like type 1 diabetes in rare cases (0.2% of patients). Adverse events have been reported in up to 60% of patients, with serious side effects in some cases.
26789How is the drug Dato-DXd + Pembrolizumab unique for advanced lung cancer?
This drug combination is unique because it combines pembrolizumab, a standard treatment for certain lung cancers, with datopotamab deruxtecan, a novel antibody-drug conjugate targeting a specific protein on cancer cells, potentially offering more effective treatment for patients who do not respond well to existing therapies.
1231011Eligibility Criteria
This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) who haven't had previous systemic treatments. Participants must have high PD-L1 expression, good physical condition, adequate bone marrow function, and no significant heart issues. They should not have certain infections like hepatitis B/C or HIV, severe eye diseases, recent vaccines, autoimmune diseases, other cancers within a set time frame, or untreated brain metastases.Inclusion Criteria
Sign and date the Tissue Screening and Main Informed Consent Forms, prior to the start of any study-specific qualification procedures.
I have given a tissue sample for TROP2 protein testing.
Participants eligible for inclusion in the study must meet all inclusion criteria within 28 days of randomization into the study.
+10 more
Exclusion Criteria
I have not received a live vaccine in the last 30 days.
I do not have untreated brain metastases or spinal cord compression.
I had radiotherapy less than 4 weeks ago or received high-dose lung radiation in the last 6 months.
+14 more
Trial Timeline
Tissue Screening
Participants undergo tissue screening to confirm eligibility based on PD-L1 expression and histology
2-4 weeks
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either pembrolizumab alone or in combination with Dato-DXd
Up to 44 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 71 months
Participant Groups
The study compares the effectiveness of Dato-DXd combined with pembrolizumab versus pembrolizumab alone in treating NSCLC without specific genetic changes. It aims to determine which treatment works better for this type of lung cancer by randomly assigning participants to one of the two groups.
2Treatment groups
Experimental Treatment
Active Control
Group I: Pembrolizumab + Datopotamab Deruxtecan (Dato-DXd)Experimental Treatment2 Interventions
Participants will be randomized to receive 200 mg pembrolizumab followed by 6.0mg/kg Dato-DXd.
Group II: PembrolizumbActive Control1 Intervention
Participants will be randomized to receive 200 mg pembrolizumab.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Dana-Farber Cancer InstituteBoston, MA
McGill University Health CentreMontreal, Canada
Dartmouth Hitchcock Medical CenterLebanon, NH
Cooperman Barnabas Medical CenterNew Brunswick, NJ
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Daiichi Sankyo, Inc.Lead Sponsor
Daiichi SankyoLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
AstraZenecaIndustry Sponsor
References
TROPION-Lung08: phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC. [2023]Pembrolizumab monotherapy is a standard first-line treatment for PD-L1-high advanced non-small-cell lung cancer (NSCLC) without actionable genomic alterations (AGA). However, few patients experience long-term disease control, highlighting the need for more effective therapies. Datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface antigen 2-directed antibody-drug conjugate, showed encouraging safety and antitumor activity with pembrolizumab in advanced NSCLC. We describe the rationale and design of TROPION-Lung08, a phase III study evaluating safety and efficacy of first-line Dato-DXd plus pembrolizumab versus pembrolizumab monotherapy in patients with advanced/metastatic NSCLC without AGAs and with PD-L1 tumor proportion score ≥50%. Primary end points are progression-free survival and overall survival; secondary end points include objective response rate, duration of response, safety and presence of antidrug antibodies. Clinical trial registration: NCT05215340 (ClinicalTrials.gov).
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated.
Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. [2023]Data of first-line ramucirumab plus pembrolizumab treatment of programmed death-ligand 1 (PD-L1)-positive NSCLC (cohort E) are reported (NCT02443324).
Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]Pembrolizumab is a highly selective IgG4 kappa isotype monoclonal antibody against the programmed cell death-1 (PD-1) molecule. In the treatment of non-small cell lung cancer (NSCLC), pembrolizumab has demonstrated significant efficacy, significant survival outcomes, long-lasting responses, and a good safety profile compared with cytotoxic chemotherapy.
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation. [2022]Parts 4 and 5 of the phase 1/2 KEYNOTE-022 study investigated the maximum tolerated dose (MTD), safety, and efficacy of pembrolizumab plus trametinib in solid tumours and BRAF wild-type melanoma.
Pembrolizumab (Keytruda). [2023]The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced overall response rates (ORRs) of 21-34%. It was superior to another immune checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma. In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of 19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a valid response predictor. Molecular analysis also showed that tumors with high gene mutation burdens, which might result in the formation of more tumor-related neo-antigens, had better responses to pembrolizumab. In malignancies including lymphomas and other solid tumors, preliminary data showed that ORRs of around 20-50 % could be achieved. Adverse events occurred in up to 60% of patients, but grade 3/4 toxicities were observed in
Pemetrexed maintenance with or without pembrolizumab in non-squamous non-small cell lung cancer: A cross-trial comparison of KEYNOTE-189 versus PARAMOUNT, PRONOUNCE, and JVBL. [2021]To characterize the benefit-risk profile of pemetrexed and platinum in combination with pembrolizumab in patients with non-squamous non-small cell lung cancer in the KEYNOTE-189 study, with reference to historical pemetrexed maintenance data from the PARAMOUNT, PRONOUNCE, and JVBL randomized studies.
Safety of pembrolizumab in recurrent or advanced gastric cancer expressing PD-L1 refractory to platinum and fluoropyrimidine. [2022]Pembrolizumab is a highly selective fully human immunoglobulin 4 monoclonal antibody against programmed death 1 (PD-1). Phase II and III trials have demonstrated that pembrolizumab has antitumor activity in previously treated patients with advanced gastric cancer (AGC).
PD-L1 immunohistochemistry comparison of 22C3 and 28-8 assays for gastric cancer. [2022]Nivolumab and pembrolizumab are promising therapies for gastric adenocarcinoma. The 22C3 and 28-8 pharmDx immunohistochemistry assays for programmed death ligand-1 scoring criteria have been developed. This study compared the programmed death ligand-1 staining patterns of gastric adenocarcinoma evaluated by the 22C3 and 28-8 pharmDx assays.