Phase 3 Study of T-DXd and Rilvegostomig versus Standard of Care in Advanced HER2-expressing Biliary Tract Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Sep 2025 → ongoing

Decision date (initial)

2025-06-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-508057-19-00

ClinicalTrials.gov

NCT06467357

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety, Efficacy

The primary objective of this study is to assess the efficacy of T-DXd with rilvegostomig vs Standard of Care (SoC) in terms of OS in the FAS (HER2 IHC 3+) population.

Secondary objectives 1

1. Key secondary efficacy objectives are to assess the following: a) efficacy of T-DXd with rilvegostomig vs SoC in terms of OS in the FAS (HER2 IHC 3+/2+) population; b) efficacy of T-DXd monotherapy vs SoC in terms of OS in the FAS (HER2 IHC 3+) population and c) efficacy of T-DXd monotherapy vs SoC in terms of OS in the FAS population.

Conditions and MedDRA coding

Advanced HER2-expressing Biliary Tract Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.
2. 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.
3. Histologically confirmed HER2-expressing (IHC 3+ or IHC 2+) BTC.
4. 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.
5. Has at least one target lesion assessed by the Investigator based on RECIST v1.1. (randomized portion only)
6. WHO/ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
7. Adequate organ and bone marrow function within 14 days before randomization.
8. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential.
9. Minimum life expectancy of 12 weeks

Exclusion criteria 17

1. Prior exposure to other HER2 targeting therapies, ADCs, immune checkpoint inhibitors and therapeutic anticancer vaccines.
2. 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).
3. Prior pneumonectomy (complete)
4. 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.
5. Active primary immunodeficiency, known uncontrolled active HIV infection or HCV
6. Histologically confirmed ampullary carcinoma
7. 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.
8. 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
9. 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
10. 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
11. 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
12. Corrected QT interval (QTcF) prolongation to > 470 msec (females) or > 450 msec (males) based on average of the screening triplicate 12-lead ECG
13. History of (non-infectious) ILD/pneumonitis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
14. 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.
15. 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).
16. 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.
17. History of organ transplants or allogenic stem cell transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+) population

Secondary endpoints 14

1. To evaluate the efficacy of T-DXd with rilvegostomig vs SoC in terms of OS in the FAS population (HER2 IHC 3+/2+).
2. To evaluate the efficacy of T-DXd monotherapy vs SoC in terms of OS in the FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations.
3. To further evaluate efficacy of T‑DXd with rilvegostomig or in monotherapy vs SoC in terms of PFS in the FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations.
4. To further evaluate the efficacy of T-DXd with rilvegostomig or in monotherapy vs SoC in terms of ORR in the FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations.
5. To further evaluate efficacy of T‑DXd with rilvegostomig or in monotherapy vs SoC in terms of DoR in patients with HER2‑expressing BTC in the FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations.
6. To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of OS, PFS, DoR and ORR in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations.
7. To assess the safety and tolerability of T‑DXd with rilvegostomig or in monotherapy vs SoC.
8. To assess the safety and tolerability of TDXd with rilvegostomig vs T-DXd monotherapy.
9. To describe patient-reported tolerability of TDXd with rilvegostomig or in monotherapy in comparison to SoC based on a summary of symptomatic AEs and overall side-effect bother.
10. To describe patient-reported tolerability of TDXd with rilvegostomig in comparison to T-DXd monotherapy based on a summary of symptomatic AEs and overall side-effect bother.
11. To assess time to deterioration in physical functioning in patients treated with T-DXd with rilvegostomig or in monotherapy vs SoC.
12. To assess time to deterioration in physical functioning in patients treated with T-DXd with rilvegostomig vs T-DXd monotherapy.
13. To assess the PK of T-DXd, total anti-HER2 antibody, DXd and rilvegostomig in serum.
14. To investigate the immunogenicity of T-DXd and of rilvegostomig.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 3

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

10 EU/EEA countries · 65 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 107 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications