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Closed (no longer recruiting)Last updated: 2 February 2024

DESTINY-Lung03: This phase I study is investigating how safe, tolerable and effective targeted therapy (trastuzumab deruxtecan) is alone, and in combination with immunotherapy (durvalumab) and chemotherapy (cisplatin, carboplatin or pemetrexed) in people with HER2-positive, advanced or metastatic, non-small cell lung cancerA Phase Ib Multicenter, Open-label Dose-escalation Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Durvalumab in Combination With Cisplatin, Carboplatin or Pemetrexed in First-line Treatment of Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) and Human Epidermal Growth Factor Receptor 2 Overexpression (HER2+) (DESTINY-Lung03)

Clinical summary

Summary

This study will consist of two parts. Part 1 is a dose-escalation study design allowing the assessment of safety, tolerability and recommended dose levels of the combination of trastuzumab deruxtecan (T-DXd) and durvalumab plus cisplatin, carboplatin or pemetrexed. Part 1 will involve people on their second or third-line of treatment. In Part 2, expansions in the treatment naïve setting on any recommended dose level may take place to study preliminary efficacy as well. In Part 1, the dose of T-DXd and the chemotherapeutic components on Arms 1A, 1B and 1C (cisplatin, carboplatin or pemetrexed) will be modified during the dose-escalation part in order to find the recommended phase 2 dose (RP2D). The dose of durvalumab will remain fixed in this part of the study. Arm 1D will ass T-DXd as monotherapy. All treatments will be administered via an intravenous (IV) infusion. The Part 2 of the study may be initiated following Part 1, at the discretion of the sponsor.

Conditions

This trial is treating patients with non-small cell lung cancer.

Cancer

Lung Cancers Lung cancer

Age

People18 - 120

Phase

I

Trial Acronym

DESTINY-Lung03

More information

Trial Identifiers

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Trial sponsor

AstraZeneca

Scientific Title

A Phase Ib Multicenter, Open-label Dose-escalation Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Durvalumab in Combination With Cisplatin, Carboplatin or Pemetrexed in First-line Treatment of Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) and Human Epidermal Growth Factor Receptor 2 Overexpression (HER2+) (DESTINY-Lung03)

Eligibility

Inclusion

  • Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC
  • Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting.
  • Part 3: Treatment-naïve for non curative treatment for locally advanced or metastatic NSCLC.
  • Part 3: Patients must have tumors without known genomic alterations or actionable driver kinases, as determined by existing local test results, for which approved therapies are available are allowed. Patients who received prior adjuvant, neoadjuvant chemotherapy, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred > 6 months from end of last therapy
  • HER2overexpression status as determined by central review of tumor tissue
  • WHO / ECOG performance status of 0 or 1
  • Measurable target disease assessed by the investigator using RECIST 1.1
  • Has protocol defined adequate organ and bone marrow function
  • Part 3: Minimum body weight of 35 kg.

Exclusion

  • HER2 mutation if previously known
  • Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
  • Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder and prior pneumonectomy
  • Active primary immunodeficiency known HIV infection, or active hepatitis B (positive hepatitis B virus surface antigen or hepatitis B virus core antibody) or hepatitis C infection
  • Active infection including tuberculosis and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
  • Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
  • Medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke
  • Cardiomyopathy of any etiology, symptomatic CHF (as defined by New York Heart Association Class > II), unstable angina pectoris, history of MI within the past 12 months, or cardiac arrhythmia (Part 3).
  • A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or CART (Concentrated Ascites Reinfusion Therapy)
  • Unresolved toxicities not yet resolved to Grade ≤ 1 or baseline from previous anticancer therapy OR prior discontinuation of any planned study therapy due to toxicity.
  • must not have any medical contraindication to platinum-based chemotherapy.
  • Part 3 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting.

Inclusion

  • You have been diagnosed with cancer, but have not received any treatment.
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • Your cancer has not spread to other parts of the body.
  • Your cancer has spread to other parts of the body.

Exclusion

  • You have certain types of non-cancer medical conditions.
Message

Clinical trials have complex eligibility criteria.

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