Trastuzumab Deruxtecan for Non-Small Cell Lung Cancer

Recruiting at 151 trial locations

Overseen By AstraZeneca Lung Cancer Study Locator Service

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

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

No Placebo Group All 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 Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Until progression, assessed up to approximately 28 months

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, Trastuzumab Deruxtecan (also known as Enhertu or DS-8201a), for individuals with Non-Small Cell Lung Cancer (NSCLC) that has specific genetic mutations in HER2 Exon 19 or 20. Researchers aim to determine if this treatment outperforms current standard care options. It targets those who have not yet begun treatment and have advanced or metastatic NSCLC with these specific mutations. As a Phase 3 trial, it represents the final step before FDA approval, providing an opportunity to access a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that Trastuzumab Deruxtecan is likely to be safe for humans?

Research has shown that trastuzumab deruxtecan, the treatment under study for non-small cell lung cancer with HER2 mutations, has undergone safety testing. In earlier studies, common side effects included a drop in white blood cell count, occurring in about 73% of participants. Other side effects were nausea, tiredness, and reduced appetite, but many patients managed these effects.

The findings indicated a good balance between benefits and risks, with benefits outweighing side effects for many patients. Some experienced interstitial lung disease, though this was less common. Overall, the data suggests that trastuzumab deruxtecan is generally well-tolerated, which is encouraging for prospective trial participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NSCLC?

Most treatments for non-small cell lung cancer (NSCLC) involve a combination of chemotherapy and immunotherapy, like platinum-based drugs, pemetrexed, and pembrolizumab. But Trastuzumab Deruxtecan (T-DXd) works differently. It’s an antibody-drug conjugate, which means it combines a targeted antibody with a potent chemotherapy agent. This unique mechanism allows it to deliver chemotherapy directly to cancer cells, potentially increasing effectiveness while minimizing damage to healthy cells. Researchers are excited because this targeted approach could improve outcomes for patients with specific types of NSCLC that overexpress certain proteins, offering a more personalized treatment option.

What evidence suggests that Trastuzumab Deruxtecan might be an effective treatment for Non-Small Cell Lung Cancer?

Research has shown that Trastuzumab Deruxtecan (T-DXd), which participants in this trial may receive, works effectively and provides lasting results in treating HER2-mutant Non-Small Cell Lung Cancer (NSCLC). Studies have found that it targets cancer cells with HER2 mutations, leading to noticeable tumor shrinkage. In past cases, patients experienced long-lasting benefits from this treatment. It specifically attacks cancer cells, sparing most healthy cells, which enhances its safety. While some patients have experienced side effects like lung problems, these are uncommon. Overall, the results are promising for those with HER2-mutant NSCLC. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

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.

My cancer cannot be cured with surgery or radiation and may have spread.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Trastuzumab Deruxtecan

Trial Overview 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.

How Is the Trial Designed?

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

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

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Daiichi Sankyo, Inc.

Industry Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Published Research Related to This Trial

In a phase 1 trial involving 44 patients with HER2-positive gastric or gastro-oesophageal junction cancer, trastuzumab deruxtecan demonstrated a manageable safety profile, with the most common serious side effects being anemia and decreases in blood cell counts, but no drug-related deaths were reported.

The treatment showed promising preliminary activity, with 43.2% of patients achieving a confirmed objective response, indicating its potential effectiveness in patients who had previously been treated with trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Shitara, K., Iwata, H., Takahashi, S., et al.[2020]

In a phase 1 trial involving 115 patients with HER2-positive breast cancer previously treated with trastuzumab emtansine, trastuzumab deruxtecan demonstrated a manageable safety profile, with 59.5% of patients achieving a confirmed objective response.

Despite some serious treatment-emergent adverse events, including cases of interstitial lung disease and pneumonitis, the preliminary efficacy results suggest that trastuzumab deruxtecan is a promising treatment option, warranting further investigation in larger clinical trials.

NCBI (Pubmed)

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. Tamura, K., Tsurutani, J., Takahashi, S., et al.[2020]

Trastuzumab deruxtecan (Enhertu®) has been shown to be significantly more effective than standard chemotherapy in improving overall survival and achieving objective responses in adults with advanced HER2-positive gastric or gastro-oesophageal junction adenocarcinoma, based on results from the phase II DESTINY-Gastric01 trial.

The treatment is generally well-tolerated, with common side effects including nausea and fatigue, but it does carry important safety warnings for interstitial lung disease and embryo-foetal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma. Kang, C.[2023]

Trastuzumab deruxtecan (ENHERTU®) is an innovative treatment that combines an antibody targeting HER2 with a DNA topoisomerase I inhibitor, specifically designed for HER2-expressing solid tumors, including various types of cancer.

It received accelerated approval in the USA based on the promising results from the phase 2 DESTINY-Breast01 trial, which focused on patients with advanced HER2-positive breast cancer who had already undergone multiple treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: First Approval. Keam, SJ.[2020]

Trastuzumab deruxtecan (Enhertu®) has been shown to significantly improve progression-free survival in adults with unresectable or metastatic HER2-positive breast cancer compared to the previous standard treatment, trastuzumab emtansine, in a pivotal phase 3 trial.

The treatment has a generally manageable safety profile, although it is associated with common adverse events like hematological and gastrointestinal disorders, and requires careful monitoring for interstitial lung disease (ILD)/pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. Nie, T., Blair, HA.[2023]

Citations

1. enhertuhcp.com enhertuhcp.com/en/nsclc/efficacy/efficacy-data

In activating HER2-mutant 2L mNSCLC at 5.4 mg/kg Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40749900/

Final Analysis Results and Patient-Reported Outcomes ... Conclusions: T-DXd demonstrated strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4 ...

3. jto.org jto.org/article/S1556-0864(25)00981-5/fulltext

Final Analysis Results and Patient-Reported Outcomes ... Conclusions. T-DXd demonstrated strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4 ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2112431

Trastuzumab Deruxtecan in HER2-Mutant Non–Small-Cell ... Trastuzumab deruxtecan showed durable anticancer activity in patients with previously treated HER2-mutant NSCLC. The safety profile included interstitial lung ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12378165/

Trastuzumab deruxtecan for the treatment of metastatic non ... Results. All the four patients had metastatic lung adenocarcinoma and reached partial response to T-DXd treatment. A 57-year-old female patient ...

6. enhertuhcp.com enhertuhcp.com/en/nsclc/additional-data

Additional Data | ENHERTU® (fam-trastuzumab ... In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (73%), ...

7. daiichisankyo.us daiichisankyo.us/press-releases/-/article/daiichi-sankyo-presents-updated-results-for-fam-trastuzumab-deruxtecan-ds-8201-in-patients-with-her2-mutated-or-her2-expressing-non-small-cell-lung-ca

Press Releases Daiichi Sankyo Presents Updated Results for [Fam-] Trastuzumab Deruxtecan (DS-8201) in Patients with HER2 Mutated or HER2 Expressing Non-Small Cell Lung Cancer ...