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 Partisipants with Advanced Solid Tumours Expressing Claudin18.2. NOTE: Official Title should have no more than 240 characters.

JRCT ID: jRCT2031230569

Registered date:16/01/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Gastric cancer, Gastroesophageal junction cancer, Pancreatic Adenocarcinoma
• Date of first enrollment: 29/01/2024
• Target sample size: 123
• Countries of recruitment: Australia,Japan,Canada,Japan,Malaysia,Japan,Singapore,Japan,Republic of Korea,Japan,Spain,Japan,Taiwan,Japan,United Kingdom,Japan,United States of America,Japan,Republic of Moldova,Japan,Georgia,Japan
• Study type: Interventional

Intervention(s)

Drug: AZD0901
Antibody-drug conjugate/Biologic
Other Name: CMG901

Drug: 5-Fluorouracil
Chemotherapy agents
Other Names: 5-FU

Drug: l-leucovorin
Chemotherapy agents
Other Names: I-LV

Drug: Irinotecan
Chemotherapy agents
Other Names: Camptosar

Drug: Nanoliposomal Irinotecan
Chemotherapy agents
Other Names:ONIVYDE

Drug: Gemcitabine
Chemotherapy agents
Other Names:Gemzar

Outcome(s)

Primary Outcome

- 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.]
To investigate the safety and tolerability, of AZD0901 monotherapy or in combination with anti-cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2.

- Objective Response Rate (ORR). [ Time Frame: From date of first dose of AZD0901 up until progression, or the last evaluable assessment on the absence of progression.]
Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR) as determined by the Investigator at local site as per RECIST v1.1.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Master Inclusion Criteria applicable to both sub sutudies:

- Participant must be 18 years or more 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 or more.

- Adequate organ and bone marrow function as defined by protocol.

- Body weight > 35kg.

- 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.

Exclude criteria

Master Exclusion Criteria applicable to both sub sutudies:

- Unstable or active peptic ulcer disease or digestive tract bleeding including but not limited to clinically significant bleeding on 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 Grade 2 or more 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 HAR2-positive (3+ by IHC, or 2+ by IHC, and positive by ISH) or indeterminate GC/GEJC.

- 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.

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT06219941