2023-508275-37-00
Recruiting
Phase 1/2
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
- Phase
- Phase 1/2
- Status
- Recruiting
- Sponsor
- AstraZeneca AB
- Enrollment
- 9
- Locations
- 5
- Primary Endpoint
- Incidence of AEs and SAEs, Changes form baseline in laboratory parameters, vital signs, ECGs, and physical examination, Rate of AEs leading to discontinuation of AZD0901, Occurrence of DLTs (Japanese safety cohort in sub study 1, and safety run-in in sub study 2)
Overview
Brief Summary
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. To evaluate the preliminary anti-tumour activity of AZD0901 monotherapy or in combination with anti-cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2 in terms of ORR.
Study Design
- Allocation
- Not Applicable
- Primary Purpose
- Survival follow-up period
- Masking
- None
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •both sub studies: Participant must be ≥ 18 years or the legal age of consent at the time of signing the ICF.
- •Sub study 3: 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.
- •Sub study 1: Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction.
- •Sub study 1: Advanced or metastatic GC/GEJC.
- •Sub study 1: The first approximately 30 participants in each arm are required to provide and archival sample up to 24 months old or a fresh tumour biopsy at screening. For participants enrolled after the first 30 in each arm, a fresh baseline biopsy is mandatory at screening, and on treatment biopsy is mandatory unless it is not clinically feasible.
- •Sub study 1: Maximum 2 prior lines of systemic treatment for unresectable or metastatic disease, including CLDN18.2 targeting mAbs (other prior CLDN18.2 targeting modalities are not allowed. Prior MMAE ADC are also not allowed). (a) Progression within 6 months/183 days of last dose of prior adjuvant or neoadjuvant therapy (including herceptin, immunotherapy) is considered as equivalent to progression on one regimen for advanced or metastatic disease. (b) If one of the components of prior combination therapy is discontinued due to AE and the other continued, this is considered to be ‘one prior regimen’. (c) If the prior therapy is discontinued due to poor tolerability or AE and the patient is switched to another therapy with no documented progression, this is considered to be ‘one prior regimen’. (d) Change in dose or route of administration (eg, IV or oral fluoropyrimidine) of prior regimen without progression is considered to be ‘one prior regimen’.
- •Sub study 2: Participants diagnosed with histologically confirmed metastatic or advanced PDAC.
- •Sub study 2: Availability of an archival sample up to 24 months old or a fresh tumour biopsy taken at screening.
- •Sub study 2: No prior treatments for unresectable or metastatic disease. Participants must not have received systemic therapy for mPDAC. Prior neoadjuvant/adjuvant chemotherapy is permitted as long as participants progressed ≥ 6 months from the last dose.
- •both sub studies: Participant with previously confirmed positive CLDN18.2 test result using the same assay in other AstraZeneca studies are eligible without prospective CLDN18.2 test at pre-screening.
Exclusion Criteria
- •both 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.
- •Sub study 1: Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age.
- •Sub study 1: The use of concomitant medications known to prolong the QT/QTc interval (refer to Section 6.9 for list of prohibited medications).
- •Sub study 2: Exclusion criterion 1 is specific for Arms 1, 1A, 1B and 1C (5FU specific). Exclusion criteria 2, 3, and 4 are specific for Arm 1 and Arm 1B (Irinotecan specific).
- •Sub study 2: Known DPD enzyme deficiency based on local testing where testing is SoC.
- •Sub study 2: Use of strong inhibitor or inducer of UGT1A
- •Sub study 2: Use of strong inhibitors or inducers of CYP3A
- •Strong inducers of CYP3A4 should be stopped at least 2 weeks before and strong inhibitors of CYP3A4 should be stopped at least 1 week before the first dose of Irinotecan.
- •Sub study 2: Known homozygous for the UGT1A1*28 allele based on local testing where testing is SoC.
- •both sub studies: Participants with clinically significant ascites that require regular drainage.
Outcomes
Primary Outcomes
Incidence of AEs and SAEs, Changes form baseline in laboratory parameters, vital signs, ECGs, and physical examination, Rate of AEs leading to discontinuation of AZD0901, Occurrence of DLTs (Japanese safety cohort in sub study 1, and safety run-in in sub study 2)
Incidence of AEs and SAEs, Changes form baseline in laboratory parameters, vital signs, ECGs, and physical examination, Rate of AEs leading to discontinuation of AZD0901, Occurrence of DLTs (Japanese safety cohort in sub study 1, and safety run-in in sub study 2)
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
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
Secondary Outcomes
- Overall Survival - The time from date of first dose/randomisation until the date of death due to any cause
- Progression-free survival is defined as the time from first dose/date of randomisation until progression per RECIST v1.1 asassessed by the Investigator at local site, or death due to any cause, regardless of whether the participant withdraws from randomized therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST v1.1 progression.
- DoR - The time from the date of first documented confirmed response until date of first documented progression per RECISTv1.1 or death due to any cause.
- TTR - The time from first dose/date of randomisation until the first documentation of a subsequently confirmed objective response per RECIST v1.1 as assessed by the Investigator at local site.
- DCR at 12 weeks is defined as the percentage of participants who have a confirmed CR or PR or who have SD per RECIST v1.1as assessed by the Investigator at local site and derived from the raw tumour data for at least 11 weeks after date of first dose/date of randomisation.
- Tumor Size - The best percentage change from baseline in tumor size is the largest decrease (or smallest increase) from baseline for a participant, using RECIST v1.1 assessments.
- To characterise the PK of AZD0901 monotherapy or in combination with anti cancer agents in participants with advancedor metastatic solid tumours expressing CLDN18.2.
- To determine the immunogenicity of AZD0901 monotherapy or in combination with anti-cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2.
- To investigate baseline and/or on-treatment tissue-based RNA,DNA, and/or proteins, and association with clinical activity ofAZD0901 (substudy 1).
- DRR-12: DRR-12 is defined as the percentage of subjects with a durable response at 12 weeks. DRR-24: DRR-24 is defined as the percentage of subjects with a durable response at 24 weeks.
Investigators
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB
Study Sites (5)
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