A Study of AK130 in Combination With AK112 for the Treatment of Advanced Biliary Tract Cancer

Official title

An Open Label, Multicenter, Phase Ib/II Clinical Study of AK130 in Combination With AK112 for the Treatment of Advanced Biliary Tract Cancer

Overview

There're 2 parts in this interventional study: 1. The goal of phase Ib trial is to evaluate the safety and tolerability of AK130 in combination with AK112 therapy for the purpose of observing the incidence of dose limit toxicity (DLT) as well as the confirmation of maximum tolerable dose (MTD) in the treatment of advanced biliary tract cancer (BTC), so as to determine the recommended phase 2 dose (RP2D) in the second part of the trial. 2. The goal of phase II trial is to evaluate the safety and efficacy of AK112 in combination with AK130 therapy or monotherapy in the treatment of advanced BTC.

Interventions

• Drug AK112
  Following a predefined dose and date.
• Drug AK130
  Following a predefined dose and date.

Primary outcome measures

• Number of subjects with dose limiting toxicities (DLTs) [Time frame: During the first three weeks.]
• Number of subjects with adverse events (AEs) [Time frame: From the time of informed consent signed through 30 days after the last dose of study drug or starting new anti-cancer therapy.]
• Objective Response Rate (ORR) (Phase II) [Time frame: Through study completion, an average of 2 years.]

Secondary outcome measures (6)

• Objective Response Rate (ORR) (Phase Ib) [Time frame: Through study completion, an average of 2 years.]
• Disease control rate (DCR) [Time frame: Through study completion, an average of 2 years]
• Duration of Response (DoR) [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months]
• Time to response (TTR) [Time frame: From date of randomization until the date of first documented response, assessed up to 24 months]
• Progression Free Survival (PFS) [Time frame: Through study completion, an average of 2 years.]
• Overall survival (OS) [Time frame: Through study completion, an average of 2 years.]

Eligibility criteria

Inclusion criteria

• Be able and willing to provide written informed consent.
• Have a life expectancy of at least 3 months.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Subjects with histologically and/or cytologically confirmed advanced or metastatic biliary tract malignancies (including only intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma; excluding ampullary carcinoma), who have experienced treatment failure following prior first-line systemic therapy.
• According to RECIST v1.1, there is at least one untreatable measurable lesion, or a measurable lesion with clear imaging progression after local treatment, suitable for repeated and accurate measurement.
• Has adequate organ function.
• All subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
• Able to to comply with all requirements of study participation (including all study procedures).

Exclusion criteria

• Except for BTC, the subjects had other malignant tumors within the 3 years prior to enrollment. Subjects with other malignant tumors that have been cured through local treatment are not excluded, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast cancer in situ.
• There is central nervous system (CNS) metastasis, spinal cord compression, or meningeal metastasis.
• There are pleural effusion, pericardial effusion, or ascites with clinical symptoms or requiring repeated drainage.
• Prior administration of any immunotherapy targeting immune mechanisms other than PD-1/PD-L1 inhibitors.
• There is a history of non infectious pneumonia that requires systemic glucocorticoid treatment.
• History of severe bleeding tendency or coagulation dysfunction.
• Previous history of myocarditis, cardiomyopathy, and malignant arrhythmia.
• Any arterial or severe venous thromboembolism events, transient ischemic attacks, cerebrovascular accidents, hypertensive crises, or hypertensive encephalopathy occurred within 6 months prior to the first administration of medication.
• Pregnant or lactating female subject.
• Any prior or concurrent disease, treatment, or laboratory test abnormality that may confuse study results, affect subjects' full participation in the study, or may not be in their best interest to participate.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking Union Medical College Hospital, Chinese Academy of Medical Sciences — Beijing

Identifiers

NCT: NCT06938321 · AK130-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗