~386 spots leftby Feb 2028

Dato-DXd + Pembrolizumab for Advanced Lung Cancer (TROPION-Lung08 Trial)

Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Daiichi Sankyo, Inc.
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.
Is the drug combination of Datopotamab Deruxtecan and Pembrolizumab promising for advanced lung cancer?Yes, the combination of Datopotamab Deruxtecan and Pembrolizumab is promising for advanced lung cancer. It has shown encouraging safety and antitumor activity, and it is being tested in a major study to see if it works better than Pembrolizumab alone.2481011
What safety data is available for Dato-DXd and Pembrolizumab in lung cancer treatment?The safety data for Pembrolizumab (Keytruda) includes its use in various cancers, including non-small cell lung cancer (NSCLC). Pembrolizumab has been associated with immune-related adverse events (irAEs), such as type 1 diabetes mellitus, occurring in 0.2% of cases. In NSCLC, adverse events occurred in up to 60% of patients, with grade 3/4 toxicities observed. However, specific safety data for the combination of Dato-DXd and Pembrolizumab in lung cancer is not detailed in the provided research.13789
What data supports the idea that Dato-DXd + Pembrolizumab for Advanced Lung Cancer is an effective treatment?The available research shows that Dato-DXd combined with Pembrolizumab has shown promising results in treating advanced lung cancer. In a study called TROPION-Lung08, this combination was compared to Pembrolizumab alone, which is a common treatment for this type of cancer. The study focused on patients with a specific type of lung cancer and found that the combination treatment had encouraging safety and antitumor activity. This suggests that Dato-DXd + Pembrolizumab could be more effective than using Pembrolizumab by itself.256811
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop your current medications. However, there is a requirement for an adequate treatment washout period before starting the trial, which suggests you might need to stop certain medications. Please consult with the trial coordinators for specific guidance.

Eligibility 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

I have given a tissue sample for TROP2 protein testing.
My lung cancer has been confirmed by a biopsy and meets certain stage criteria.
My tumor shows high PD-L1 expression.
I am fully active or restricted in physically strenuous activity but can do light work.
My cancer does not have certain genetic changes according to tests.

Exclusion Criteria

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.
I am currently on IV medication for an uncontrolled infection.
I have received specific treatments for my non-small cell lung cancer.
I have an autoimmune disease.
I have received a transplant from another person.
I do not have serious heart problems.
I do not have active or uncontrolled hepatitis B or C.
I have received treatment for advanced lung cancer before.
I have an immune system disorder or have been on steroids or other immune-weakening drugs in the last week.
I have a serious eye condition affecting my cornea.
My HIV infection is not well controlled.

Treatment Details

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
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Who is running the clinical trial?

Daiichi Sankyo, Inc.Lead Sponsor
Daiichi SankyoLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
AstraZenecaIndustry Sponsor

References

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
[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.
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.
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).
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.
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).
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.
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.
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.
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.
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).