AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2

Official title

A Phase II, Open-label, Multi-centre Study to Evaluate Safety, Tolerability, Efficacy, PK, and Immunogenicity of AZD0901 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Tumours Expressing Claudin 18.2 (CLARITY-PanTumour01)

Overview

The purpose of this study is to assess the safety, tolerability, efficacy, pharmacokinetics (PK), and immunogenicity of AZD0901 as monotherapy and in combination with anti-cancer agents in participants with locally advanced unresectable or metastatic solid tumours expressing CLDN18.2.

Detailed description

This open-label, multi-centre study consists of individual sub studies, each evaluating the safety and tolerability of AZD0901.

Sub study 1 will investigate the safety, tolerability, and anti-tumour activity of AZD0901 monotherapy in participants with advanced or metastatic gastric esophageal cancer expressing CLDN18.2. Participants will receive AZD0901 monotherapy via intravenous (IV) infusion and will be randomised in to one of 2 arms.

Sub study 2 will consist of two parts, a safety run-in and a dose expansion part to investigate the safety and efficacy of AZD0901 in combination with different chemotherapy agents in participants with pancreatic cancer. Substudy 3 will investigate the safety, tolerability, and anti-tumour activity of AZD0901 monotherapy in participants with advanced or metastatic Biliary tract cancer.

Interventions

• Drug AZD0901
  Antibody-drug conjugate/Biologic
• Drug 5-Fluorouracil
  Chemotherapy agents
• Drug Leucovorin
  Chemotherapy agents
• Drug l-leucovorin
  Chemotherapy agents
• Drug Irinotecan
  Chemotherapy agents
• Drug Nanoliposomal Irinotecan
  Chemotherapy agents
• Drug Gemcitabine
  Chemotherapy agents

Primary outcome measures

• Incidence of adverse events (AEs), serious AEs (SAEs). Changes from baseline in clinical laboratory parameters, vital signs, ECGs and physical examination. Rate of AEs leading to discontinuation of AZD0901, Occurrence of DLTs. [Time frame: 30 days post treatment completion. AE Follow Up for 90 days post AZD0901 discontinuation.]
• Objective Response Rate (ORR). [Time frame: From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).]

Secondary outcome measures (9)

• Overall Survival (OS) [Time frame: From date of first dose/randomisation until the date of death due to any cause (approximately 2 years).]
• Progression Free Survival (PFS) [Time frame: From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 2 years).]
• Duration of Response (DoR) [Time frame: From the date of first documented confirmed response until date of documented progression (approximately 2 years).]
• Disease control rate (DCR) [Time frame: Up to 11 weeks post date of first dose/randomisation]
• Percentage change in tumor size [Time frame: From start through to study completion.]
• Serum concentration of AZD0901 (total ADC), total antibody (conjugated and unconjugated) and total unconjugated MMAE [Time frame: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.]
• Serum PK parameters of AZD0901, total antibody (conjugated and unconjugated) and MMAE including but not limited to AUC, Cmax, tmax, clearance and half-life, as data allow. [Time frame: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.]
• Clinical activity by baseline and/or on-treatment tissue-based biomarkers including, but not limited to, gene expression, mutation profiles, DNA damage, protein expression, immune response and/or mechanisms of resistance. [Time frame: From date of first dose of AZD0901 up to 7 weeks.]
• ADA status will be determined along with prevalence and incidence of anti-drug antibodies to AZD0901, and titer established. [Time frame: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.]

Eligibility criteria

The list below is a summarised eligibility criteria for the study - refer to the study protocol for full criteria.

Master Inclusion Criteria applicable to all sub studies:

• Participant must be ≥ 18 years or the legal age of consent at the time of signing the ICF.
• Participants who are CLDN18.2 positive.
• Must have at least one measurable lesion according to RECIST v1.1.
• ECOG performance status of 0 to 1 with no deterioration over the previous 2 weeks prior first day of dosing.
• Predicted life expectancy of ≥ 12 weeks.
• Adequate organ and bone marrow function as defined by protocol.
• Body weight > 35 kg.
• Participants are willing to comply with contraception requirements.

Sub study 1 Specific Inclusion criteria:

• Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction.
• Advanced or metastatic GC/GEJC.
• Maximum 2 prior lines of systemic treatment for unresectable or metastatic disease.

Sub study 2 Specific Inclusion criteria:

• Participants diagnosed with histologically confirmed metastatic or advanced PDAC.
• Availability of an archival sample or a fresh tumour biopsy taken at screening.
• No prior treatments for unresectable or metastatic disease. Prior neoadjuvant/adjuvant chemotherapy is permitted as long as participants progressed ≥ 6 months (183 days) from the last dose.

Sub study 3 Specific Inclusion criteria

• Histologically confirmed, unresectable advanced, or metastatic adenocarcinoma of biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma (NOTE: Ampullary cancers are not eligible).
• Documented radiographic or clinical disease progression on or after at least one prior regimen and maximum 2 prior lines of systemic treatment for unresectable or metastatic disease.

Master Exclusion Criteria applicable to all sub studies:

• Unstable or active peptic ulcer disease or digestive tract bleeding including but not limited to clinically significant bleeding in the setting of prior CLDN18.2 directed therapy.
• Participants with clinically significant ascites that require drainage.
• A history of drug-induced non-infectious ILD/pneumonitis.
• Central nervous system metastases or CNS pathology.
• Peripheral neuropathy, sensory, or motor ≥ Grade 2 at screening.
• History of another primary malignancy.
• Prior exposure to any MMAE-based ADC.
• Prior exposure to any CLDN18.2 targeted agents except anti-CLDN18.2 monoclonal antibody.

Sub study 1 Specific Exclusion criteria:

• Participants with HER2-positive (3+ by IHC, or 2+ by IHC, and positive by ISH) or indeterminate GC/GEJC unless they have failed/not tolerated/or are not eligible for standard anti-HER2 therapy, where available.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
• The use of concomitant medications known to prolong the QT/QTc interval.

Sub study 2 Specific Exclusion criteria:

• Known DPD enzyme deficiency based on local testing where testing is SoC.
• Use of strong inhibitor or inducer of UGT1A1.
• Use of strong inhibitors or inducers of CYP3A4.
• Known homozygous for the UGT1A1\*28 allele based on local testing where testing is SoC.

Sub study 3 Specific Exclusion criteria

• Clinically significant biliary obstruction that has not resolved before enrollment.

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

United States · 7 centers

• Research Site — Orange
• Research Site — Palo Alto
• Research Site — Santa Rosa
• Research Site — Louisville
• Research Site — Commack
• Research Site — Providence
• Research Site — Houston

Japan · 6 centers

• Research Site — Chūōku
• Research Site — Kashiwa
• Research Site — Kitaadachi-gun
• Research Site — Kōtoku
• Research Site — Nagoya
• Research Site — Osakasayama-shi

Malaysia · 5 centers

• Research Site — George Town
• Research Site — Johor Bahru
• Research Site — Kuala Lumpur
• Research Site — Kuala Selangor
• Research Site — Kuching

South Korea · 5 centers

• Research Site — Gyeonggi-do
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul

Taiwan · 5 centers

• Research Site — Kaohsiung City
• Research Site — Taichung
• Research Site — Tainan
• Research Site — Taipei
• Research Site — Taoyuan

Canada · 4 centers

• Research Site — Kingston
• Research Site — Toronto
• Research Site — Montreal
• Research Site — Sherbrooke

Singapore · 4 centers

• Research Site — Bukit Merah
• Research Site — Singapore
• Research Site — Singapore
• Research Site — Singapore

United Kingdom · 4 centers

• Research Site — Glasgow
• Research Site — Leeds
• Research Site — London
• Research Site — Oxford

Australia · 3 centers

• Research Site — Melbourne
• Research Site — Murdoch
• Research Site — Randwick

Spain · 3 centers

• Research Site — Barcelona
• Research Site — Madrid
• Research Site — Madrid

China · 2 centers

• Research Site — Changsha
• Research Site — Chengdu

Poland · 2 centers

• Research Site — Krakow
• Research Site — Warsaw

Georgia · 1 center

• Research Site — Tbilisi

Moldova · 1 center

• Research Site — Chisinau

Identifiers

NCT: NCT06219941 · D9800C00001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗