A Modular Multi-Basket Trial to Improve Personalized Medicine in Cancer Patients (Basket of Baskets)

Sponsor
Vall d'Hebron Institute of Oncology
Study ID
NCT03767075
Phase
PHASE2
Status
Recruiting
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Conditions

  • Advanced Solid Tumor

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Atezolizumab — DRUG
    1200 mg, administered IV, once every 3 weeks
  • Futibatinib — DRUG
    20 mg administered orally, once daily (QD) continuously in 28-day cycles.
  • Amivantamab — DRUG
    1050 mg administered IV for body weight \< 80 kg and 1400 mg for body weight \>= 80 kg mg once weekly in Cycle 1 (with a split dose on Days 1-2) and then every 2 weeks in subsequent cycles (28-day cycles)

Study Details

The global objective of this Basket of Basket study is to evaluate the antitumor activity of each matched therapies that will be evaluated through the study in small molecularly selected populations. The objective of module 1 wil be to determine the overall response rate (ORR) at 12 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of atezolizumab in each of the arms of the module. All patients in genomically selected populations will receive atezolizumab 1200 mg IV every 3 weeks. The objective of module 2 wil be to determine the overall response rate (ORR) at 16 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of futibatinib in each of the arms of the module. All patients in genomically selected populations will receive will receive futibatinib, 20 mg, once daily (QD) in 28-day cycles. The objective of module 3 wil be to determine the overall response rate (ORR) at 12 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of amivantamab in each of the arms of the module. All patients in genomically selected populations will receive amivantamab 1050 mg intravenously (IV) for body weight \< 80 kg and 1400 mg for body weight \>= 80 kg mg once weekly in Cycle 1 (with a split dose on Days 1-2) and then every 2 weeks in subsequent cycles (28-day cycles).

Key Dates

Start date
Dec 10, 2018
Status verified
Apr 2024
Primary completion
May 31, 2025
Completion
Nov 30, 2026

Study Design

Enrollment
1,000 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Module 1 - Atezolizumab
    Genomically selected populations will all receive the same drug * Arm 1A: BRCA1 or BRCA2 mutations * Arm 1B: MLH1, MSH2, MSH6, or PMS2 mutations * Arm 1C: tumors with POLE mutation, POLD1 mutation * Arm 1D: hypermutated tumors * Arm 1E: tumors with other mutations in DNA-repair genes * Arm 1F: tumors with amplified PDL1 * Arm 1G: tumours with CDK12 mutations Subjects will be recruited and allocated to arms according to their biomarker profile. It is assumed that 1000 subjects will need to be screened in part A in order to enroll 120 patients in part B of module 1.
  • Experimental: Module 2 - Futibatinib
    Genomically selected populations will all receive the same drug * Arm 2A: Known pathogenic FGFR1-3 mutations * Arm 2B: Variants of unknown significance in FGFR1-3 with functional relevance or pathogenic FGFR4 mutations. * Arm 2C: Highly amplified FGFR1-3 with high FGFR1-3 mRNA (with the exception of gastric and breast cancer) * Arm 2D: Highly amplifiedFGFR1-3 without high FGFR1-3 mRNA (with the exception of gastric and breast cancer) Subjects will be recruited and allocated to arms according to their biomarker profile. It is assumed that 2000 subjects will need to be screened in part A in order to enroll 80 patients in part B of module 2.
  • Experimental: Module 3 - Amivantamab
    Genomically selected populations will all receive the same drug * Arm 3A: kinase domain mutations/ MET fusion-genes (including intragene exon skipping MET-MET fusions) * Arm 3B: MET copy number gain (equivalent CNG ≥6) (exception: colorectal cancer) * Arm 3C: EGFR mutations (exception: primary lung malignancies) Subjects will be recruited and allocated to arms according to their biomarker profile. It is assumed that 1725 subjects will need to be screened in part A in order to enroll 69 patients in part B of module 3.

Primary Outcome Measure

Overall response rate [ Time Frame: From the first dose date of study treatment to first CR or PR, whichever came earlier, up to 12 weeks (Module 1 & 3) and 16 weeks (Module 2) ]

Central Contacts

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