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

NCT03767075 | Recruiting Phase 2

• 2 other identifiers: VHIO170022017-005108-89
• Study Type: interventional
• Target: 1,000
• Locations: 7 countries
• Sites: 8

Brief Summary

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).

Conditions

Advanced Solid Tumor

Keywords

Advanced Solid Tumor; Cancer; Atezolizumab; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Proportion of patients with a partial response \[PR\] or complete response \[CR\] per RECIST v1.1.

  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)

Secondary Outcomes (5)

• Progression free survival (PFS by RECIST 1.1)

  From initiation of treatment to objective progression or death from any cause, whichever occurs first, up to two years

• Overall Survival

  From initiation of treatment to death from any cause, up to two years

• Duration of response

  From documentation of the first CR or PR to the time of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death (up to apprixmatelly 6 months).

• Health-related quality of life (HRQoL)

  Baseline up to data cut-off, up to two years.

• Incidence and severity of adverse events

  From initiation of treatment to 30 days (all adverse events), and 90 days (all SAEs and AESIs), then any SAE considered treatment-related.

Study Arms (3)

Module 1 - Atezolizumab

EXPERIMENTAL

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.

Drug: Atezolizumab

Module 2 - Futibatinib

EXPERIMENTAL

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.

Drug: Futibatinib

Module 3 - Amivantamab

EXPERIMENTAL

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.

Drug: Amivantamab

Interventions

Atezolizumab DRUG

1200 mg, administered IV, once every 3 weeks

Module 1 - Atezolizumab

Futibatinib DRUG

20 mg administered orally, once daily (QD) continuously in 28-day cycles.

Also known as: TAS-120

Module 2 - Futibatinib

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)

Also known as: JNJ-372

Module 3 - Amivantamab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically or cytologically confirmed malignancy that is metastatic or unresectable, who have progressed to standard therapy, who are receiving a standard anticancer treatment, but no subsequent approved treatment would be available upon progression, who are unable to receive standard therapy, or for whom standard therapy does not exist.
• Patient must have ECOG performance status of 0 or 1.
• Subjects must be 18-year-old or older.
• Subjects must have measurable disease according to RECIST 1.1.
• Subjects must have enough tumour tissue for molecular analysis.
• Subjects providing formalin-fixed paraffin embedded tissue (FFPE) must provide a minimum amount of tissue ranging from 28 to 36 slides depending on the sample tumour cellularity. If there is not enough archival tissue to meet this criterion, the patient must undergo a tumour biopsy.
• Subjects providing fresh frozen tissue must provide 5 core biopsies or equivalent.
• Fresh frozen tissue must be preferentially collected from a tumour biopsy; hence, subjects must have disease amenable to be biopsied. Otherwise, the patient should have fresh frozen tumour tissue stored in a biobank or biorepository.
• Efforts will be made to provide fresh frozen tissue in at least one quarter of the participating subjects. The proportion of subjects that might provide fresh frozen tissue might change based on the results from the molecular analysis.
• Since some of the tests are performed in FFPE tissue, subjects providing fresh frozen tissue from a recent biopsy will have part of the sample processed in FFPE as per Laboratory manual.
• Subjects must have adequate haematological, renal, and hepatic function.
• For subjects requiring a tumour biopsy: subjects must have adequate coagulation function.
• Subjects must be willing to participate in a clinical trial with a matched therapy according to the molecular profile of his/her tumour.

You may not qualify if:

• Subjects with leptomeningeal disease should be excluded from this clinical trial.
• Subjects with known unstable brain metastases should be excluded from this clinical trial. Exception: Subjects who have undergone surgery and/or radiotherapy and in which brain metastases remain stable or decrease in size for six months after having completed therapy.
• Subjects with spinal cord compression not definitively treated with surgery and/or radiation.
• Subjects with uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure, LVEF \< 50%, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects with inability to swallow tablets or capsules.
• Subjects with known HIV, hepatitis B or hepatitis C infection.
• Subjects with known history of malabsorption.
• Eligibilty Criteria (PART B - iBASKET)
• Subjects must have metastatic or unresectable malignant tumour, histologically or cytological confirmed and progressing to current therapy. Tumours must be refractory to standard therapy or for which standard therapy does not exist, or subjects may be unable to receive standard therapy.
• Patient must have ECOG performance status of 0 or 1.
• Subjects must be 18-year-old or older.
• Subjects must have measurable disease according to RECIST 1.1.
• Subjects must be willing to participate in a clinical trial with a matched therapy according to the molecular profile of his/her tumour.
• Tumours must harbour the following alterations.
• Subjects must have adequate hematological, renal, and hepatic function.

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology: lead
• Roche Pharma AG: collaborator
• Iqvia Pty Ltd: collaborator
• Taisho Pharmaceutical Co., Ltd.: collaborator
• Janssen, LP: collaborator

Study Sites (8)

Institut Gustave Roussy

Villejuif, 94800, France

RECRUITING

Deutsches Krebsforschungszentrum (NCT/DKFZ)

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Universitätsklinikum Dresden

Dresden, 01307, Germany

RECRUITING

Instituto Nazionale dei Tumori di Milano

Milan, 20133, Italy

RECRUITING

Nederland Kanker Instituut (NKI)

Amsterdam, 1066, Netherlands

RECRUITING

Hospital Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Karolinska University Hospital Solna

Stockholm, 17176, Sweden

RECRUITING

Cancer Research UK Cambridge Centre

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

atezolizumab; futibatinib; amivantamab

Study Officials

• Jordi Rodon, MD

  MD Anderson

  STUDY CHAIR

Central Study Contacts

Marta Carboneras

CONTACT

+34 686 187 838; mcarboneras@vhio.net

Susana Muñoz

CONTACT

+34 934 893 000; smunoz@vhio.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: no masking is used. All involved know the identity of the intervention assignment
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * Part A includes a molecular profiling program for subjects with advanced solid tumors (iPROFILER) and a molecular tumor board to select the most appropriate treatment based on the molecular alterations found in the iPROFILER. * Part B includes iBASKET, a modular investigator initiated basket study for subjects with selected molecular alterations.

Study Record Dates

• First Submitted: November 14, 2018
• First Posted: December 6, 2018
• Study Start: December 10, 2018
• Primary Completion: May 1, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

GB (1); SE (1); DE (2); FR (1); NL (1); ES (1); IT (1)