DS-8201a + Pembrolizumab for Breast and Lung Cancer

Recruiting at 40 trial locations

Overseen By AZ Breast Cancer Study Navigators

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Daiichi Sankyo

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 42

115 Participants Needed

Trial Summary

What is the purpose of this trial?

This two-part study will include a dose escalation part to determine the recommended dose for expansion of DS8201a and pembrolizumab and a dose expansion part to evaluate efficacy, safety, and tolerability of the combination.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications. However, there is a requirement for an adequate treatment washout period before enrollment, and certain medications like systemic corticosteroids and prior systemic anticancer therapies must be stopped within specific timeframes before starting the trial. It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial requires an adequate treatment washout period before enrollment, which means you may need to stop taking certain medications for a period of time before joining the study. However, the specific medications you need to stop are not detailed in the protocol.

What data supports the idea that DS-8201a + Pembrolizumab for Breast and Lung Cancer is an effective drug?

The available research shows that DS-8201a, also known as trastuzumab deruxtecan, has been effective in treating HER2-positive breast cancer. In a study, a majority of patients with advanced HER2-positive breast cancer responded to the drug, with a median response duration of 20.7 months. Another study reported a 60.3% response rate in patients who had previously received other treatments, with the response lasting a median of 14.8 months. These results led to the drug's approval for treating certain types of breast cancer, indicating its effectiveness. However, the research does not provide specific data on its effectiveness for lung cancer or when combined with Pembrolizumab. ^{1 2 3 4 5}

What data supports the effectiveness of the drug DS-8201a (Trastuzumab deruxtecan) for breast and lung cancer?

Trastuzumab deruxtecan (DS-8201a) has shown effectiveness in treating HER2-positive breast cancer, with a significant number of patients responding to the drug and a median response duration of 20.7 months. It has also been approved for HER2-low breast cancer, indicating its potential effectiveness in similar conditions. ^{1 2 3 4 5}

What safety data exists for DS-8201a and Pembrolizumab in breast and lung cancer treatment?

For DS-8201a (fam-trastuzumab deruxtecan-nxki, T-DXd, ENHERTU), safety data from the DESTINY-Breast01 trial and study DS8201-A-J101 indicate risks of interstitial lung disease, neutropenia, and left ventricular dysfunction, with common adverse reactions including nausea, fatigue, and anemia. For Pembrolizumab (KEYTRUDA, MK-3475), a phase II trial in non-small cell lung cancer reported interim safety results, but specific adverse effects were not detailed in the provided abstracts. ^{1 4 5 6 7}

What safety data exists for DS-8201a and Pembrolizumab in humans?

Trastuzumab deruxtecan (DS-8201a) has been associated with serious side effects like interstitial lung disease (lung inflammation), neutropenia (low white blood cell count), and heart problems. Common side effects include nausea, fatigue, and hair loss. Pembrolizumab has been studied in lung cancer patients, but specific safety details from that study are not provided. ^{1 4 5 6 7}

Is the drug Pembrolizumab, Trastuzumab deruxtecan (DS-8201a) a promising treatment for breast and lung cancer?

Yes, the drug Pembrolizumab, Trastuzumab deruxtecan (DS-8201a) is promising for treating breast and lung cancer. It has been approved by the US Food and Drug Administration for certain types of breast cancer, showing positive responses in patients. It has also shown potential in treating lung cancer, as seen in early clinical trials. ^{1 2 3 6 8}

What makes the drug DS-8201a + Pembrolizumab unique for breast and lung cancer?

This drug combination is unique because it combines Trastuzumab deruxtecan (DS-8201a), a targeted therapy that delivers chemotherapy directly to cancer cells, with Pembrolizumab, an immunotherapy that helps the immune system attack cancer. This dual approach targets both HER2-positive breast cancer and non-small cell lung cancer, potentially offering a new treatment option for patients with these conditions. ^{1 2 3 6 8}

Research Team

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

Adults (≥18 years) with advanced/metastatic breast cancer that is HER2-positive or HER2-low, and those with similar stages of NSCLC. Participants must have tried all other beneficial treatments or be unable to tolerate them. They should not have had prior treatment with pembrolizumab/DS-8201a, severe heart issues within the last 6 months, active hepatitis B/C, certain lung conditions, autoimmune diseases requiring steroids/immunosuppressants, or a history of severe allergic reactions to similar drugs.

Inclusion Criteria

You have at least one identifiable and measurable tumor according to a specific set of guidelines.

I am fully active or restricted in physically strenuous activity but can do light work.

My breast cancer is advanced or has spread, and tests show it's HER2 positive.

Exclusion Criteria

I still have side effects from past cancer treatments.

Your heart's electrical activity (QT interval) is longer than usual, which can be risky for your health.

I have been treated with drugs targeting PD-1 or PD-L1.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Escalating doses of DS-8201a in combination with pembrolizumab are assessed to determine the recommended dose for expansion

6 weeks

Every 21 days

Dose Expansion

Participants receive DS-8201a at the recommended dose in combination with pembrolizumab to evaluate efficacy, safety, and tolerability

Varies by cohort

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pembrolizumab
• Trastuzumab deruxtecan (DS-8201a)

Trial Overview The trial tests DS8201a combined with Pembrolizumab in two parts: first to find the best dose and then to check how well it works and its safety. It's for people whose breast or lung cancer has spread and expresses a protein called HER2. The study aims to see if this drug combo can help when other treatments haven't worked.

Participant Groups

Group I: Part 1 (Dose Escalation) Experimental Treatment 2 Interventions

HER2-positive breast cancer, HER2-low expressing breast cancer, HER2-expressing NSCLC, and HER2-mutant NSCLC participants who received escalating doses of DS8201a (initial dose 3.2 mg/kg Q3W) and pembrolizumab 200 mg.

Group II: HER2-positive breast cancer (Part 2 Dose Expansion) Experimental Treatment 2 Interventions

HER2-positive breast cancer participants with prior ado-trastuzumab emtansine (T-DM1) with disease progression and who received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Group III: HER2-mutant NSCLC (Part 2 Dose Expansion) Experimental Treatment 2 Interventions

HER2-mutant NSCLC participants who had not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents and received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Group IV: HER2-low breast cancer (Part 2 Dose Expansion) Experimental Treatment 2 Interventions

HER2 low breast cancer participants with prior failed standard treatments who received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Group V: HER2-expressing NSCLC (Part 2 Dose Expansion) Experimental Treatment 2 Interventions

HER2-expressing NSCLC participants who had not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents and received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Daiichi Sankyo

Lead 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.

Lead 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

AstraZeneca UK Limited

Collaborator

Trials

1

Recruited

120+

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

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

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

Fam-trastuzumab deruxtecan-nxki (T-DXd) has been approved for treating HER2-low metastatic breast cancer, showing significant improvements in progression-free survival (PFS) and overall survival (OS) in a phase III trial with 557 patients.

The study demonstrated a 50% reduction in the risk of disease progression and a 36% reduction in the risk of death compared to standard chemotherapy, with a safety profile consistent with previous uses of T-DXd and no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

US Food and Drug Administration Approval Summary: Fam-Trastuzumab Deruxtecan-nxki for Human Epidermal Growth Factor Receptor 2-Low Unresectable or Metastatic Breast Cancer. Narayan, P., Dilawari, A., Osgood, C., et al.[2023]

In a phase 2 study involving 184 patients with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab emtansine, trastuzumab deruxtecan demonstrated a significant response rate of 60.9%, with a median response duration of 14.8 months.

While trastuzumab deruxtecan showed promising efficacy, it was associated with notable adverse effects, including interstitial lung disease in 13.6% of patients, highlighting the need for careful monitoring of pulmonary symptoms during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. Modi, S., Saura, C., Yamashita, T., et al.[2021]

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]

Fam-trastuzumab deruxtecan-nxki (ENHERTU) received accelerated FDA approval for treating HER2-positive breast cancer in patients who have already undergone two or more anti-HER2 therapies, based on a study involving 184 patients that showed a confirmed overall response rate of 60.3%.

While ENHERTU is effective, it carries significant risks, including severe interstitial lung disease and neutropenia, highlighting the importance of monitoring for serious side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. Narayan, P., Osgood, CL., Singh, H., et al.[2022]

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Trastuzumab deruxtecan (T-DXd) was evaluated for safety in 1457 patients across 8 clinical trials, revealing that gastrointestinal disorders and blood-related issues were the most common adverse events, with neutropenia being the most severe (21.4% incidence).

The study highlighted significant concerns regarding interstitial lung disease (10.9% incidence) and decreased left ventricular ejection fraction (1.2% incidence), suggesting that while T-DXd is generally well tolerated, these specific side effects require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study. Guo, Z., Ding, Y., Wang, M., et al.[2023]

Trastuzumab deruxtecan (DS-8201a) is effective in treating HER2-positive solid cancers, particularly breast and gastric cancers, with median progression-free survival (PFS) ranging from 9.0 to 22.1 months and objective response rates (ORR) between 37% and 79.9%.

The most common adverse events (AEs) associated with DS-8201a include nausea, decreased appetite, and fatigue, with significant grade 3 or higher AEs being decreased neutrophil count and anemia, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy profile of Trastuzumab deruxtecan in solid cancer: pooled reanalysis based on clinical trials. Xu, H., Zhang, H., Guo, W., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

US Food and Drug Administration Approval Summary: Fam-Trastuzumab Deruxtecan-nxki for Human Epidermal Growth Factor Receptor 2-Low Unresectable or Metastatic Breast Cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. [2021]

3. 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]

4. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. [2022]

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

Trastuzumab Deruxtecan: First Approval. [2020]

6. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy profile of Trastuzumab deruxtecan in solid cancer: pooled reanalysis based on clinical trials. [2022]