1170 Participants Needed

Dato-DXd + Pembrolizumab for Non-Small Cell Lung Cancer

Recruiting at 259 trial locations
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Overseen ByDaiichi Sankyo Contact for Clinical Trial Information
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

What data supports the effectiveness of the drug combination Dato-DXd + Pembrolizumab for Non-Small Cell Lung Cancer?

Research shows that pembrolizumab, when combined with chemotherapy drugs like carboplatin and pemetrexed, is effective as a first-line treatment for advanced non-small cell lung cancer. Pemetrexed combined with cisplatin has shown a response rate of up to 44.8% in non-small cell lung cancer, indicating that these components can be effective in treating this type of cancer.12345

What safety data exists for Dato-DXd + Pembrolizumab treatment in humans?

Pembrolizumab (Keytruda) has been studied for safety in non-small cell lung cancer, showing some side effects like pneumonitis (lung inflammation) in 1%-5% of patients. Pemetrexed and platinum drugs, when combined with pembrolizumab, have been associated with various side effects, including fatigue, blood and digestive issues, and skin reactions. These treatments have been generally safe but can cause serious side effects in some cases.26789

What makes the drug combination of Dato-DXd and Pembrolizumab unique for treating non-small cell lung cancer?

The combination of Dato-DXd and Pembrolizumab is unique because it includes a novel antibody-drug conjugate, Dato-DXd, which targets a specific protein on cancer cells, potentially enhancing the effectiveness of Pembrolizumab, an existing immunotherapy, in patients with advanced non-small cell lung cancer who have high PD-L1 expression.12101112

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 in combination with pemetrexed and platinum chemotherapy in participants with no prior therapy for advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).

Research Team

GC

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

Adults over 18 with advanced non-squamous NSCLC who haven't had systemic cancer treatment, have specific levels of TROP2 and PD-L1 proteins, no major gene mutations treatable by approved therapies, good performance status, and no significant health issues like uncontrolled heart disease or active infections. Pregnant women and those with certain lung diseases or recent vaccinations are excluded.

Inclusion Criteria

My cancer can be measured by scans.
My tumor's PD-L1 level is below 50%.
Sign and date the Main Informed Consent Form (ICF), prior to the start of any study-specific qualification procedures.
See 8 more

Exclusion Criteria

I am not pregnant, breastfeeding, nor planning to become pregnant.
I do not have active or uncontrolled hepatitis B or C.
You have other health problems, heart disease, mental health issues, or use drugs or alcohol excessively.
See 15 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive randomized treatment with Dato-DXd and pembrolizumab with or without platinum chemotherapy

Up to 57 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 57 months

Treatment Details

Interventions

  • Carboplatin
  • Cisplatin
  • Datopotamab Deruxtecan
  • Pembrolizumab
  • Pemetrexed
Trial Overview The trial is testing the effectiveness of Dato-DXd combined with pembrolizumab versus pembrolizumab with pemetrexed and platinum chemo in first-line treatment for advanced NSCLC. It aims to see which combination works better for patients who meet specific biological criteria.
Participant Groups
3Treatment groups
Experimental Treatment
Active Control
Group I: Dato-DXd + Pembrolizumab + Platinum ChemotherapyExperimental Treatment4 Interventions
Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 200 mg pembrolizumab plus platinum chemotherapy (cisplatin 75 mg/m\^2 or carboplatin area under the curve \[AUC) 5\]).
Group II: Dato-DXd + PembrolizumabExperimental Treatment2 Interventions
Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 200 mg pembrolizumab.
Group III: Pembrolizumab + Pemetrexed + Platinum ChemotherapyActive Control4 Interventions
Participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m\^2 pemetrexed plus platinum chemotherapy (cisplatin 75 mg/m\^2 or carboplatin area under the curve \[AUC) 5\]).

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

Who Is Running the Clinical Trial?

Daiichi Sankyo

Lead Sponsor

Trials
443
Recruited
493,000+
Hiroyuki Okuzawa profile image

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe profile image

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Daiichi Sankyo, Inc.

Lead Sponsor

Trials
390
Recruited
442,000+
Yuki Abe profile image

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa profile image

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

AstraZeneca

Industry Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Merck Sharp & Dohme LLC

Industry Sponsor

Trials
4,096
Recruited
5,232,000+
Chirfi Guindo profile image

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis profile image

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.
The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.
Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29).Renaud, E., Ricordel, C., Corre, R., et al.[2023]
In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.
The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience.Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]
Pemetrexed is an effective cytotoxic agent approved for first-line treatment of non-small cell lung cancer (NSCLC) in combination with cisplatin, showing promise in phase II and III trials.
The toxicity profile of pemetrexed is comparable to other NSCLC treatments, making it a safe option for patients, and its use in postinduction maintenance therapy is currently being evaluated in a phase III study.
Pemetrexed as first-line therapy for non-squamous non-small cell lung cancer.Ricciardi, S., Tomao, S., de Marinis, F.[2021]

References

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]
Pemetrexed as first-line therapy for non-squamous non-small cell lung cancer. [2021]
Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. [2017]
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]
Toxic epidermal necrolysis after pemetrexed and cisplatin for non-small cell lung cancer in a patient with sharp syndrome. [2015]
Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies. [2018]
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]
Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung cancer: A post hoc analysis of KEYNOTE-189. [2023]
TROPION-Lung08: phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC. [2023]
Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study. [2019]
12.United Statespubmed.ncbi.nlm.nih.gov
Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]
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