371 Participants Needed

Datopotamab Deruxtecan + Immunotherapy for Non-Small Cell Lung Cancer

(TROPION-Lung04 Trial)

Recruiting at 59 trial locations
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Overseen ByAstraZeneca Lung Cancer Study Locator Service
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: AstraZeneca
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This study will assess safety, tolerability, and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy with or without carboplatin in participants with advanced or metastatic non-small cell lung cancer (NSCLC).

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is the combination of Datopotamab Deruxtecan and Durvalumab safe for humans?

Durvalumab, one of the drugs in the combination, has shown acceptable tolerability in patients with non-small cell lung cancer and other solid tumors, although treatment-related toxicity is an important consideration. Ongoing studies are expected to provide more detailed safety data.12345

What makes the drug Datopotamab Deruxtecan + Durvalumab unique for non-small cell lung cancer?

This drug combination is unique because it combines Datopotamab Deruxtecan, a TROP2-directed antibody-drug conjugate, with Durvalumab, an immunotherapy that blocks PD-L1, potentially enhancing the immune system's ability to fight cancer cells in non-small cell lung cancer.16789

Research Team

GC

Global Clinical Leader

Principal Investigator

Daiichi Sankyo, Inc.

Eligibility Criteria

Adults with advanced or metastatic non-small cell lung cancer (NSCLC) who are either treatment-naïve or have had one prior chemotherapy without immune checkpoint inhibitors. Participants must have good organ function, measurable disease, no severe illnesses, and an ECOG performance status of 0 or 1. Those with certain genetic alterations in NSCLC or a history of other cancers are excluded.

Inclusion Criteria

You have a disease that can be measured according to specific guidelines within the 28 days before starting treatment.
I am 18 years or older and have signed the consent form.
My advanced lung cancer does not have EGFR or ALK mutations.
See 5 more

Exclusion Criteria

I have severe lung problems due to a recent illness.
I do not have active brain metastases or spinal cord compression.
I do not have an infection needing IV drugs.
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dato-DXd in combination with immunotherapy with or without carboplatin. Part 1 involves dose escalation or confirmation, and Part 2 involves dose expansion.

4 cycles of carboplatin (approximately 12 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of disease control rate and pharmacokinetic parameters.

9 months

Long-term follow-up

Participants are monitored for overall survival and other secondary outcomes.

Approximately 60 months

Treatment Details

Interventions

  • Carboplatin
  • Datopotamab deruxtecan
  • Durvalumab
Trial OverviewThe trial is testing the combination of Datopotamab deruxtecan (Dato-DXd), a new drug, with immunotherapy agents MEDI5752/AZD2936 and Durvalumab, plus Carboplatin for some groups. It aims to evaluate safety and how well these treatments work together in patients.
Participant Groups
15Treatment groups
Experimental Treatment
Group I: Cohort 9Experimental Treatment3 Interventions
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
Group II: Cohort 8Experimental Treatment3 Interventions
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
Group III: Cohort 7Experimental Treatment3 Interventions
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
Group IV: Cohort 6Experimental Treatment2 Interventions
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
Group V: Cohort 5Experimental Treatment2 Interventions
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
Group VI: Cohort 4AExperimental Treatment3 Interventions
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + carboplatin in participants with treatment-naïve NSCLC
Group VII: Cohort 4Experimental Treatment3 Interventions
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
Group VIII: Cohort 3Experimental Treatment3 Interventions
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
Group IX: Cohort 2Experimental Treatment2 Interventions
Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
Group X: Cohort 14Experimental Treatment2 Interventions
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC
Group XI: Cohort 13Experimental Treatment2 Interventions
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
Group XII: Cohort 12Experimental Treatment2 Interventions
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
Group XIII: Cohort 11Experimental Treatment2 Interventions
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 in participants with treatment-naïve NSCLC
Group XIV: Cohort 10Experimental Treatment3 Interventions
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
Group XV: Cohort 1Experimental Treatment2 Interventions
Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy

Datopotamab deruxtecan is already approved in Japan for the following indications:

🇯🇵
Approved in Japan as Dato-DXd for:
  • HER2-negative breast cancer

Find a Clinic Near You

Who Is Running the Clinical Trial?

AstraZeneca

Lead 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

Daiichi Sankyo

Industry 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.

Industry 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

Findings from Research

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.
While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.
Durvalumab for the treatment of non-small cell lung cancer.Mezquita, L., Planchard, D.[2019]
Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.
Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors.Yang, H., Shen, K., Zhu, C., et al.[2022]
The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.
Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.
A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma.Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

References

Durvalumab for the treatment of non-small cell lung cancer. [2019]
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]
A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. [2023]
Efficacy, safety and biomarker analysis of durvalumab in patients with mismatch-repair deficient or microsatellite instability-high solid tumours. [2023]
Meta-Analysis of the Risk of Immune-Related Adverse Events With Anticytotoxic T-Lymphocyte-Associated Antigen 4 and Antiprogrammed Death 1 Therapies. [2022]
Daratumumab: First Global Approval. [2018]
Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma. [2023]
A randomized, double-blind, placebo-controlled phase 2 study of tigatuzumab (CS-1008) in combination with carboplatin/paclitaxel in patients with chemotherapy-naïve metastatic/unresectable non-small cell lung cancer. [2022]
Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report. [2021]