Trastuzumab Deruxtecan for Cancer

(DPT02 Trial)

Recruiting in Palo Alto (17 mi)

+46 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: AstraZeneca

Disqualifiers: Pneumonitis, Severe lung illness, Infection, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors. This study will consist of Part 1 which includes 7 cohorts of: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors; and Part 2 which includes 5 cohorts A to E of: A) any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer), B) any tumor type that is HER2 IHC 2+/ISH+ (excluding breast, gastric cancer, and colorectal cancer), C) HER2 IHC 2+ or 1+ endometrial cancer, D) HER2 IHC 2+ or 1+ ovarian cancer, and E) HER2 IHC 2+ or 1+ cervical cancer. Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug Trastuzumab Deruxtecan for cancer?

Trastuzumab Deruxtecan has shown effectiveness in treating HER2-positive breast cancer, with a majority of patients responding to the treatment and a median response duration of 20.7 months. It was approved by the FDA for patients with HER2-positive breast cancer who have already tried other treatments, based on a study showing a 60.3% response rate and a median duration of response of 14.8 months.

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Is Trastuzumab Deruxtecan safe for humans?

Trastuzumab Deruxtecan has been shown to have a generally manageable safety profile, but it can cause serious side effects like interstitial lung disease (lung inflammation), neutropenia (low white blood cell count), and heart problems. Common side effects include nausea, fatigue, vomiting, and hair loss.

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How is the drug Trastuzumab Deruxtecan different from other cancer treatments?

Trastuzumab Deruxtecan is unique because it combines a targeted anti-HER2 antibody with a powerful cancer-killing agent (topoisomerase I inhibitor), allowing it to specifically attack cancer cells that express the HER2 protein. This drug is particularly novel for patients with HER2-positive cancers who have already tried other treatments, offering a new option when previous therapies have failed.

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Eligibility Criteria

This trial is for people with certain HER2-expressing tumors, including ovarian, endometrial, biliary tract, and pancreatic cancers. Participants must have advanced or metastatic disease that has worsened after prior treatment or lack other treatment options. They should not have breast, colon, stomach cancer or non-small cell lung cancer and must be free of severe infections and conditions that could affect study participation.

Inclusion Criteria

My heart, kidneys, and liver are functioning well.

My cancer's HER2 status was confirmed by a test.

My cancer is one of the specified types and may express HER2.

Exclusion Criteria

I need treatment for fluid buildup in my chest, abdomen, or around my heart.

I have severe lung-related health issues.

I have had lung inflammation that needed steroids or currently have lung disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors across multiple cohorts

6-8 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 12 months

Participant Groups

The trial tests Trastuzumab deruxtecan (T-DXd) in patients with selected HER2-positive tumors to assess its effectiveness and safety. It's an open-label Phase 2 study involving multiple cohorts based on tumor type to see if T-DXd can provide clinical benefits.

Group I: Part 2 Cohort E Experimental Treatment 1 Intervention

HER2 IHC 2+ or 1+ cervical cancer

Group II: Part 2 Cohort D Experimental Treatment 1 Intervention

HER2 IHC 2+ or 1+ ovarian cancer

Group III: Part 2 Cohort C Experimental Treatment 1 Intervention

HER2 IHC 2+ or 1+ endometrial cancer

Group IV: Part 2 Cohort B Experimental Treatment 1 Intervention

Any tumor type that is HER2 IHC 2+/ISH+ (excluding breast, gastric cancer, and colorectal cancer)

Group V: Part 2 Cohort A Experimental Treatment 1 Intervention

Any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer)

Group VI: Part 1 Cohort 7 Experimental Treatment 1 Intervention

Rare tumors

Group VII: Part 1 Cohort 6 Experimental Treatment 1 Intervention

Pancreatic cancer

Group VIII: Part 1 Cohort 5 Experimental Treatment 1 Intervention

Ovarian cancer

Group IX: Part 1 Cohort 4 Experimental Treatment 1 Intervention

Endometrial cancer

Group X: Part 1 Cohort 3 Experimental Treatment 1 Intervention

Cervical cancer

Group XI: Part 1 Cohort 2 Experimental Treatment 1 Intervention

Bladder cancer

Group XII: Part 1 Cohort 1 Experimental Treatment 1 Intervention

Biliary tract cancer

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

🇺🇸 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
• Unresectable or metastatic HER2-low breast cancer
• Unresectable or metastatic HER2-positive solid tumors

🇪🇺 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 Japan as Enhertu for:

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

🇦🇺 Approved in Australia 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 Kelowna, Canada

Research Site Ottawa, Canada

Research Site Houston, TX

Research Site Quebec, Canada

More Trial Locations

Who Is Running the Clinical Trial?

AstraZeneca Lead Sponsor

Daiichi Sankyo Co., Ltd. Industry Sponsor

References

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

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. [2021] Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. In a phase 1 dose-finding study, a majority of the patients with advanced HER2-positive breast cancer had a response to trastuzumab deruxtecan (median response duration, 20.7 months). The efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab emtansine requires confirmation.

2. 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] The US Food and Drug Administration approved fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd) for the treatment of adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry 1 + or immunohistochemistry 2+/in situ hybridization-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.

3. 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.

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] On December 20, 2019, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki [DS-8201a; T-DXd; tradename ENHERTU (Daiichi Sankyo)] 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. Approval was based on data from study DS8201-A-U201 (DESTINY-Breast01) with supportive safety data from study DS8201-A-J101. The primary efficacy endpoint in DESTINY-Breast01 was overall response rate (ORR) based on confirmed responses by blinded independent central review (ICR) using RECIST v1.1 in all participants who were assigned to receive the recommended dose of 5.4 mg/kg while secondary endpoints included duration of response (DoR). The confirmed ORR based on ICR in these 184 patients was 60.3% [95% confidence interval (CI): 52.9-67.4] and the median DoR was 14.8 months (95% CI: 13.8-16.9). Interstitial lung disease, including pneumonitis, was experienced in patients treated with T-DXd and can be severe, life threatening, or fatal. In addition, neutropenia and left ventricular dysfunction were included as Warnings and Precautions in labeling. Other important common adverse reactions were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, diarrhea, and thrombocytopenia. Overall, the totality of efficacy and safety data supported the accelerated approval of T-DXd for the intended indication.

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

A Review of Fam-Trastuzumab Deruxtecan-nxki in HER2-Positive Breast Cancer. [2021] To review the pharmacology, efficacy, and safety of antibody-drug conjugate fam-trastuzumab deruxtecan-nxki in the treatment of advanced, unresectable, or metastatic breast cancer.

6. 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.

7. 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.

8. 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.