DESTINY-Biliary Tract Cancer-01: A Phase 3 Study of Trastuzumab Deruxtecan (T-DXd) and Rilvegostomig Versus Standard-of-Care Gemcitabine, Cisplatin, and Durvalumab for First Line Locally Advanced or Metastatic HER2-expressing Biliary Tract Cancer

Official Summary

The purpose of this study is to measure the efficacy and safety of T-DXd with rilvegostomig or T-DXd monotherapy compared with gemcitabine plus cisplatin and durvalumab in patients with advanced treatment naïve HER2-expressing BTC.

Eligibility Requirements

• Minimum Age: 18 Years
• Maximum Age: 99 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 620 participants

Study Arms

• Trastuzumab deruxtecan + rilvegostomig (EXPERIMENTAL)
  Trastuzumab deruxtecan (T-DXd; DS-8201a) in combination with rilvegostomig arm
• Trastuzumab deruxtecan (EXPERIMENTAL)
  Trastuzumab deruxtecan (T-DXd; DS-8201a) arm
• Standard of Care (ACTIVE_COMPARATOR)
  Gemcitabine and cisplatin in combination with durvalumab arm

Interventions

• DRUG: Gemcitabine — Standard of care chemotherapy by intravenous infusion
• DRUG: Cisplatin — Standard of care chemotherapy by intravenous infusion
• DRUG: Durvalumab — Standard of care immunotherapy by intravenous infusion
• DRUG: Trastuzumab deruxtecan — Experimental therapy by intravenous infusion
• DRUG: Rilvegostomig — Experimental therapy by intravenous infusion

Primary Outcomes

• Safety Run In: To evaluate the safety and tolerability of T-DXd with rilvegostomig (Until all patients have completed at least 1 full Cycle (each cycle is 21 days))
• Randomized Portion: To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care (SoC) in terms of Overall Survival in the FAS (HER2 IHC 3+) population (From date of treatment randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))

Secondary Outcomes

• To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+/2+) population (From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))
• To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+) population (From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))
• To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+/2+) population (From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))
• To further evaluate efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Progression Free Survival in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations (From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first (estimated to be assessed up to 50 months))
• To further evaluate efficacy of T-DXd monotherapy vs Standard of Care in terms of Progression Free Survival in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations (From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first (estimated to be assessed up to 50 months))

Eligibility Criteria

Key Inclusion Criteria:

* Male and female patients must be at least 18 years of age at the time of signing the informed consent. Other age restrictions may apply as per local regulations.
* Unresectable, previously untreated, locally advanced or metastatic biliary tract adenocarcinoma. Prior treatment in the perioperative and/or adjuvant setting is permissible provided there is \> 3 months (90 days) between the end of adjuvant treatment and the diagnosis of locally advanced or metastatic disease.
* Histologically confirmed HER2-expressing (IHC 3+ or IHC 2+) BTC.
* Patients must provide an FFPE tumor sample that is no older than 3 years for tissue-based IHC staining to centrally determine HER2 expression, PD-L1 status, and other correlatives.
* Has at least one target lesion assessed by the Investigator based on RECIST v1.1. (Randomized portion only)
* WHO/ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
* Adequate organ and bone marrow function within 14 days before randomization.
* Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential.
* Minimum life expectancy of 12 weeks.

Key Exclusion Criteria:

* Prior exposure to other HER2 targeting therapies, ADCs, immune checkpoint inhibitors and therapeutic anticancer vaccines.
* Histologically confirmed ampullary carcinoma.
* Any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the Investigator, interfere with the patient's participation in the clinical study or evaluation of the clinical study results.
* 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 randomization/enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV), unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke.
* Serious chronic gastrointestinal conditions associated with diarrhea (eg, active inflammatory bowel disease); active non-infectious skin disease (including any grade rash, urticaria, dermatitis, ulceration, or psoriasis) requiring systemic treatment.
* Active autoimmune, connective tissue or inflammatory disorders that has required systemic treatment in the past 2 years, or where there is documented, or a suspicion of pulmonary involvement at the time of screening.
* Corrected QT interval (QTcF) prolongation to \> 470 msec (females) or \> 450 msec (males) based on average of the screening triplicate 12-lead ECG.
* History of (non-infectious) ILD/pneumonitis, 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 (eg, pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion etc).
* Prior pneumonectomy (complete).
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. Patients with prior cholangitis/biliary tract infections/biliary intervention (eg, stent, external drain) should have completed a full course of antibiotics prior to randomization.
* Active primary immunodeficiency, known uncontrolled active HIV infection or HCV.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected nonmelanoma skin cancer and curatively treated in situ disease. For certain participant populations, exceptions could also include carcinomas in-situ or Ta tumors treated with curative intent.
* Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (Drainage and Cell free and Concentrated Ascites Reinfusion Therapy are not allowed within 2 weeks prior to screening assessment).
* Any concurrent anticancer treatment without an adequate washout period prior to randomization. Concurrent use of hormonal therapy for non-cancer related conditions (eg, hormone replacement therapy) is allowed.
* History of organ transplants or allogenic stem cell transplant.

Trial Locations

• Research Site, Scottsdale, Arizona, United States
• Research Site, Tucson, Arizona, United States
• Research Site, Tucson, Arizona, United States
• Research Site, Fullerton, California, United States
• Research Site, La Jolla, California, United States
• Research Site, Los Alamitos, California, United States
• Research Site, Los Angeles, California, United States
• Research Site, Los Angeles, California, United States
• Research Site, San Francisco, California, United States
• Research Site, Walnut Creek, California, United States
• ...and 10 more locations

Contact Information

• AstraZeneca Clinical Study Information Center — CONTACT
  Phone: 1-877-240-9479
  Email: information.center@astrazeneca.com

More Biliary Tract Cancer Trials

View all Biliary Tract Cancer clinical trials