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PD-1/TIGIT bispecific mAb

CompoundRilvegostomig

Area under investigation

Advanced Solid Tumors, BTCs, Gastric cancer, NSCLC, Endometrial cancer, Metastatic urothelial carcinoma, HCC, Muscle Invasive Urothelial Carcinoma

Scientific PillarImmuno-Oncology

 

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DESTINY-BTC01 trial overview

Tumor

Advanced HER2-expressing BTCs, 1L

Trial Identifier

NCT06467357

Phase

III

Regimen

T-DXd  + rilvegostomig; T-DXd; gemcitabine + cisplatin + durvalumab

Visit ct.gov

fam-trastuzumab deruxtecan-nxki in US only; trastuzumab deruxtecan in other regions of world.

Study Design

Inclusion criteria

The key inclusion criteria are-

  • Adults ≥ 18 years
  • Unresectable, previously untreated, locally advanced or metastatic BTC.
    • Prior treatment in the perioperative and/or adjuvant setting is permissible provided there is > 6 months between the end of adjuvant treatment and the diagnosis of locally advanced or metastatic disease.
  • Histologically confirmed HER2-expressing (IHC 3+/2+) BTC
  • Provision of FFPE tumor sample that is no older than 3 years
  • 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
  • Adequate organ and bone marrow function within 14 days before randomization

Reference:

Study NCT06467357. ClinicalTrials.gov website.

Exclusion criteria

The key exclusion criteria are-

  • Prior exposure to other HER2 targeting therapies, ADCs, immune checkpoint inhibitors and therapeutic anticancer vaccines
  • Histologically confirmed ampullary carcinoma
  • 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
  • History of myocardial infarction within 6 months before randomization/enrollment, symptomatic CHF (NYHA 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
  • 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
  • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
  • Active primary immunodeficiency, known uncontrolled active HIV infection or HCV

DESTINY-BTC01 Overview Modal

DESTINY-BTC01 trial overview

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Target Overview

Programmed cell death-1 (PD-1) is a cell surface receptor that interacts with 2 ligands, programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2), to deliver inhibitory signals to T cells, limiting their function.1 

T cell immunoreceptor with Ig and ITIM domains (TIGIT) is expressed on the surface of T cells and natural killer cells, and participates in a complex regulatory network involving multiple co-inhibitory receptors—CD96 and CD112R—and one competing co-stimulatory receptor, CD226 (DNAM-1). TIGIT binds to several ligands, including CD155 (PVR), CD111, CD112, CD113, and CD114 (Nectin-4), which are expressed on antigen-presenting cells (APCs) and are often upregulated on cancer cells. TIGIT binds with high affinity to CD155 and outcompetes the co-stimulatory receptor CD226. Similar to PD-1, TIGIT ligation delivers inhibitory signals to T cells, limiting their function.2

Within the preclinical setting, TIGIT and PD-1 dual blockade enhances CD8 T-cell activation and cytotoxicity against tumor cells beyond anti-PD(L)1 therapy.3

Compound Overview

Rilvegostomig (formerly AZD2936) is an investigational monovalent humanized dual-checkpoint bispecific IgG1 antibody with high affinity to PD-1 and TIGIT receptors. It is designed to deliver simultaneous and coordinated PD-1 and TIGIT blockade on the same immune effector cell. Rilvegostomig was engineered with a triple-mutation in its fragment crystallizable (Fc)-domain to minimize unwanted NK/macrophage-mediated depletion of PD1 or TIGIT-expressing effector cells.

Rilvegostomig’s bispecific format, allowing a coordinated dual checkpoint blockade, is anticipated to improve antitumor response by reinvigorating the activity of tumor-reactive immune effector cells. This simultaneous engagement of PD1 and TIGIT is expected to elicit greater immune activation than inhibiting either pathway alone.4-9

Rilvegostomig has the potential to become a next-generation IO backbone for combinations with other T cell-targeting agents, antibody-drug conjugates and standard-of-care chemotherapies.

Rilvegostomig is in Phase III ongoing clinical development in patients with advanced solid tumors, biliary tract cancer, gastric cancer, NSCLC, endometrial cancer, HCC, and urothelial cancer.

Mechanism of Action

  • Mechanism of Action

References

1. Pardoll DM. Nat Rev Cancer. 2012;12(4):252-264. 2. Qin S, Xu L, Yi M, et al. Mol Cancer. 2019;18(1):155. 3. Chu X, Tian W, Wang Z, et al. Mol Cancer. 2023;22(1):93. 4. Lee K, Malhotra D, Pryts S, et al. J Immunother Cancer. 2022;10(Suppl 2):A489. 5. Chariou P, Rothstein R, Miller C, et al. Journal for ImmunoTherapy of Cancer. 2024;12(Suppl 2):A543. 6. Ratiu J, Chariou P, Connor T, et al. J Thorac Oncol. 2025;20(1):S14-S15. 7. Ratiu J, Connor T, Roudko V, et al. Journal for ImmunoTherapy of Cancer. 2025;13. 8. Miller C, Malhotra K, Battaglia N, et al. Journal for ImmunoTherapy of Cancer. 2025;13. 9. Cazes A, Johnson Y, Chesebrough J, et al. Journal for ImmunoTherapy of Cancer. 2025;13.

 

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DESTINY-BTC01 trial overview

Tumor

Advanced HER2-expressing BTCs, 1L

Trial Identifier

NCT06467357

Phase

III

Regimen

T-DXd  + rilvegostomig; T-DXd; gemcitabine + cisplatin + durvalumab

Visit ct.gov

fam-trastuzumab deruxtecan-nxki in US only; trastuzumab deruxtecan in other regions of world.

Study Design

Inclusion criteria

The key inclusion criteria are-

  • Adults ≥ 18 years
  • Unresectable, previously untreated, locally advanced or metastatic BTC.
    • Prior treatment in the perioperative and/or adjuvant setting is permissible provided there is > 6 months between the end of adjuvant treatment and the diagnosis of locally advanced or metastatic disease.
  • Histologically confirmed HER2-expressing (IHC 3+/2+) BTC
  • Provision of FFPE tumor sample that is no older than 3 years
  • 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
  • Adequate organ and bone marrow function within 14 days before randomization

Reference:

Study NCT06467357. ClinicalTrials.gov website.

Exclusion criteria

The key exclusion criteria are-

  • Prior exposure to other HER2 targeting therapies, ADCs, immune checkpoint inhibitors and therapeutic anticancer vaccines
  • Histologically confirmed ampullary carcinoma
  • 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
  • History of myocardial infarction within 6 months before randomization/enrollment, symptomatic CHF (NYHA 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
  • 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
  • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
  • Active primary immunodeficiency, known uncontrolled active HIV infection or HCV

DESTINY-BTC01 Overview Modal

DESTINY-BTC01 trial overview

Take me to ClinicalTrials.Gov

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Abbreviations

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  • 1L

    first line

  • 5-FU

    5-fluorouracil

  • aBTC

    Advanced Biliary Tract Cancer

  • ADA

    Anti-Drug Antibodies

  • ADC

    antibody drug conjugate

  • AE

    Adverse Event

  • ALK

    anaplastic lymphoma kinase

  • ASCO/CAP

    American Society of Clinical Oncology / College of American Pathologists

  • BID

    twice daily

  • BSA

    body surface area

  • BTCs

    biliary tract cancers

  • CAPOX

    capecitabine plus oxaliplatin

  • CCA

    Cholangiocarcinoma

  • CD19

    cluster of differentiation 19

  • CHF

    congestive heart failure

  • Cmax

    maximum observed plasma concentration of a drug

  • CNS

    central nervous system

  • COPD

    chronic obstructive pulmonary disease

  • CPS

    combined positive score

  • CT

    chemotherapy

  • CTCAE

    Common Terminology Criteria for Adverse Events

  • CTLA-4

    cytotoxic T–lymphocyte-associated antigen-4

  • Ctrough

    Lowest observed concentration of study drug before the next dose is administered

  • Ctrough

    Trough Plasma Concentration

  • DL1

    Dose Level 1

  • DL2

    Dose Level 2

  • DoR

    duration of response

  • DPD

    dihydropyrimidine dehydrogenase

  • EC

    endometrial cancer

  • ECOG PS

    Eastern Cooperative Oncology Group Performance Score

  • EGFR

    epidermal growth factor receptor

  • EORTC

    European Organization for Research and Treatment of Cancer

  • FFPE

    formalin-fixed paraffin-embedded

  • FLOT

    fluorouracil, leucovorin, oxaliplatin and docetaxel

  • FOLFOX

    folinic acid (leucovorin), fluorouracil (5-FU), oxaliplatin

  • FP

    5-fluorouracil/capecitabine

  • GBC

    gallbladder cancer

  • GC

    gastric cancer

  • GEJ

    gastroesophageal junction

  • Gem-Cis

    gemcitabine and cisplatin

  • GI

    gastrointestinal

  • GHS

    global health status

  • HBV

    hepatitis B virus

  • HCV

    hepatitis C virus

  • HER2

    human epidermal growth factor receptor 2

  • HIV

    human immunodeficiency virus

  • IHC

    immunohistochemistry

  • ILD

    interstitial lung disease

  • IO

    immuno-oncology

  • ITT

    intention-to-treat

  • IV

    intravenous

  • LVEF

    left ventricular ejection fraction

  • MI

    myocardial infarction

  • MMR

    mismatch repair

  • mNSCLC

    metastatic NSCLC

  • MRI

    magnetic resonance imaging

  • NSCLC

    non-small cell lung cancer

  • ORR

    overall or objective response rate

  • OS

    overall survival

  • PD-1

    programmed cell death-1

  • PD-L1

    programmed cell death-ligand 1

  • PD-L2

    programmed cell death-ligand 2

  • PFS

    progression-free survival

  • PFS2

    time to second progression or death

  • PK

    pharmacokinetics

  • pMMR

    mismatch repair proficient

  • PRO

    patient-reported outcomes

  • PS

    phosphatidylserine

  • Q*W

    every * weeks

  • Q3W

    every 3 weeks

  • Q4W

    every 4 weeks

  • QnW

    every n weeks

  • QoL

    quality of life

  • R

    randomization

  • R0

    no residual tumor

  • R1

    microscopic residual tumor

  • RECIST v1.1

    Response Evaluation Criteria in Solid Tumors version 1.1

  • RFS

    recurrence-free survival

  • rHU

    recombinant human hyaluronidase

  • ROS1

    ROS proto-oncogene 1

  • SAE

    serious adverse event

  • SC

    subcutaneous

  • T-DXd

    fam-trastuzumab deruxtecan-nxki in US only; trastuzumab deruxtecan in other regions of world

  • TB

    tuberculosis

  • TC

    tumor cell

  • TIGIT

    T-cell immunoreceptor with immunoglobulin and ITIM domains

  • WHO

    World Health Organization

  • XELOX

    capecitabine, oxaliplatin

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

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Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
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