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)

Trial ID: NCT06219941

Interventional - Phase 2 - Recruiting

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 .

Conditions

• Gastric Cancer
• Gastroesophageal Junction Cancer
• Biliary Tract Cancer
• Pancreatic Ductal Adenocarcinoma

Interventions

• AZD0901
• 5-Fluorouracil
• Leucovorin
• l-leucovorin
• Irinotecan
• Nanoliposomal Irinotecan
• Gemcitabine

Eligibility

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.

Sponsor

AstraZeneca

Source: ClinicalTrials.gov

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