Trastuzumab Deruxtecan for Non-Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

+122 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Disqualifiers: Egfr mutations, Brain metastases, Autoimmune disorders, Myocardial infarction, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

DESTINY-Lung04 will investigate the efficacy and safety of Trastuzumab Deruxtecan (T-DXd) versus Standard of Care (SoC) as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) with HER2 Exon 19 or 20 mutations

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. However, it does mention that participants should not have had prior treatment for their advanced or metastatic lung cancer.

What data supports the effectiveness of the drug Trastuzumab Deruxtecan for treating non-small cell lung cancer?

Trastuzumab Deruxtecan has shown effectiveness in treating other HER2-positive cancers like breast and gastric cancer, where it improved survival and response rates compared to standard treatments. This suggests potential effectiveness in similar HER2-expressing tumors, such as non-small cell lung cancer.

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What safety information is available for Trastuzumab Deruxtecan (Enhertu, DS-8201a)?

Trastuzumab Deruxtecan has been generally manageable in terms of safety, with common side effects including blood and stomach issues. However, it carries warnings for lung problems (interstitial lung disease/pneumonitis) and potential harm to unborn babies, so careful monitoring is needed.

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What makes the drug Trastuzumab Deruxtecan unique for treating non-small cell lung cancer?

Trastuzumab Deruxtecan is unique because it is a HER2-targeted antibody-drug conjugate that combines a humanized anti-HER2 antibody with a topoisomerase I inhibitor, designed to target and kill cancer cells more effectively. It has shown promise in treating various HER2-expressing cancers, including breast and gastric cancers, and is being explored for non-small cell lung cancer, which may not have many standard HER2-targeted treatments.

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Eligibility Criteria

Adults with a specific type of advanced lung cancer (non-squamous NSCLC) that has certain HER2 mutations and hasn't been treated yet. They must have good heart, kidney, liver function, an ECOG performance status of 0-1, and measurable disease. Not eligible if they've had a recent heart attack or conditions like active brain metastases or autoimmune diseases.

Inclusion Criteria

My heart, kidneys, and liver are functioning well.

I have not received any treatment for my advanced or spread cancer.

I am 18 years old or older.

Exclusion Criteria

I have brain metastases, but they are currently treated and not active.

I have or might have a lung condition not caused by an infection.

My tumor has a specific change in genes like EGFR or ALK that can be treated with targeted therapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Trastuzumab Deruxtecan or Standard of Care treatment for NSCLC with HER2 mutations

Until progression, assessed up to approximately 28 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

Assessed up to approximately 28 months

Participant Groups

The trial is testing Trastuzumab Deruxtecan against standard treatments for this lung cancer type. Standard options include Cisplatin or Carboplatin combined with Pembrolizumab and Pemetrexed to see which is more effective as the first treatment.

Group I: Arm 1 Experimental Treatment 1 Intervention

Trastuzumab Deruxtecan (T-DXd)

Group II: Arm 2 Active Control 4 Interventions

Standard of Care Treatment (platinum, pemetrexed and pembrolizumab)

Trastuzumab Deruxtecan is already approved in European Union, United States, Japan for the following indications:

🇪🇺 Approved in European Union as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma

🇺🇸 Approved in United States as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma
• HER2-low breast cancer

🇯🇵 Approved in Japan as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Research Site Silver Spring, MD

Research Site New Brunswick, NJ

Research Site Orange, CA

Research Site Montvale, NJ

More Trial Locations

Who Is Running the Clinical Trial?

AstraZeneca Lead Sponsor

Daiichi Sankyo Industry Sponsor

Daiichi Sankyo, Inc. Industry Sponsor

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: First Approval. [2020] Trastuzumab deruxtecan (ENHERTU®), a HER2-directed antibody and DNA topoisomerase I inhibitor conjugate, is being developed for the treatment of HER2-expressing solid tumours, including breast cancer, gastric cancer, colorectal cancer and non-small cell lung cancer by Daiichi Sankyo Company Ltd in collaboration with AstraZeneca. Based primarily on the results of the phase 2 DESTINY-Breast01 trial, trastuzumab deruxtecan was recently approved in the USA under accelerated approval for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. This article summarizes the milestones in the development of trastuzumab deruxtecan leading to this first approval.

2. France pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. [2023] Trastuzumab deruxtecan (Enhertu®) is a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate approved in several countries, including the USA and those of the EU, for adults with unresectable or metastatic HER2-positive breast cancer who have previously received at least one prior anti-HER2-based regimen. In a pivotal phase 3 trial in this setting, intravenous trastuzumab deruxtecan demonstrated prolonged progression-free survival compared with trastuzumab emtansine (previously the recommended second-line therapy in this indication). Trastuzumab deruxtecan had a generally manageable safety and tolerability profile. Common treatment-related adverse events included haematological and gastrointestinal disorders. Interstitial lung disease (ILD)/pneumonitis is associated with a regulatory warning and requires careful monitoring. In conclusion, trastuzumab deruxtecan is a valuable new treatment option for HER2-positive breast cancer, having been shown to be effective with a generally manageable safety and tolerability profile in adults with unresectable or metastatic disease who have received one or more prior anti-HER2-based regimens.

3. France pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma. [2023] Trastuzumab deruxtecan (Enhertu®) is a human epidermal growth factor receptor type 2 (HER2)-directed antibody-drug conjugate that is approved in several countries globally for adults with advanced HER2-positive gastric or gastro-oesophageal junction (GOJ) adenocarcinoma who have received a prior trastuzumab-based regime. In the phase II DESTINY-Gastric01 trial, intravenous trastuzumab deruxtecan was significantly more effective than standard chemotherapy (physician's choice of intravenous irinotecan or paclitaxel) in achieving objective response and improving overall survival in Japanese or South Korean adults with advanced HER2-positive gastric or GOJ adenocarcinoma who had received two or more previous therapies. In the phase II DESTINY-Gastric02 trial, trastuzumab deruxtecan was able to induce durable response in adults from the USA or Europe with unresectable or metastatic HER2-positive gastric or GOJ adenocarcinoma. Trastuzumab deruxtecan was generally tolerable in these patients; the most common adverse events included nausea, neutropenia, fatigue and decreased appetite. Trastuzumab deruxtecan carries regulatory warnings (including boxed warnings in the USA) for interstitial lung disease/pneumonitis and embryo-foetal toxicity. Current evidence indicates that trastuzumab deruxtecan is an effective treatment option, and is generally tolerable, in previously treated adults with advanced HER2-positive gastric or GOJ adenocarcinoma.

4. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. [2020] Trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanised anti-HER2 antibody, cleavable peptide-based linker, and potent topoisomerase I inhibitor payload. A phase 1, non-randomised, open-label, multiple-dose study was done to assess the safety, tolerability, and activity of trastuzumab deruxtecan in HER2-expressing, advanced solid tumours. The dose escalation (part 1) has previously been reported and the recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg were established. In this Article, we report the safety and preliminary activity results from this phase 1 trial in all patients with HER2-positive advanced-stage breast cancer with previous trastuzumab emtansine treatment who received trastuzumab deruxtecan at the recommended doses for expansion.

5. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. [2020] Trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanised anti-HER2 antibody, cleavable peptide-based linker, and topoisomerase I inhibitor payload. A phase 1, non-randomised, open-label, multiple-dose study was done to assess the safety, tolerability, and activity of trastuzumab deruxtecan in HER2-expressing advanced solid tumours. The dose escalation (part 1) has previously been reported and the recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg were established. In this Article, we report the safety and preliminary activity results from this phase 1 trial in all patients with HER2-positive gastric or gastro-oesophageal junction cancer who received trastuzumab deruxtecan at the recommended doses for expansion.