This trial is a multicenter, open-label, biology driven, phase II study using a sequential Bayesian design, aiming to assess the efficacy and safety of different Matched Targeted Therapy (MTT) in independent and parallel cohorts of treatment. Patients will be assigned to a treatment cohort based on molecular alterations/characteristics detected on tumor sample from primary tumor or metastatic lesion. In this protocol, several MTTs treatment cohorts are planned. This study is designed with the flexibility to open new MTTs treatment cohorts and to close existing MTTs treatment cohorts that demonstrate no clinical benefit. Each treatment cohort will be driven separately even though procedures, quality control and reporting, will be common. The protocol will be amended in order to include new treatments or combinations that emerge as being of interest for patients with advanced/metastatic cancers. All eligible patients will receive study drugs as long as patient experiences clinical benefit in the opinion of the investigator, or until unacceptable toxicity, or until symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status, or withdrawal of consent. Patients will be permitted to continue study treatment after progressive disease according to RECIST v1.1 if they meet all of the following criteria and following validation of the Sponsor: * Evidence of clinical benefit as assessed by the investigators, * Absence of symptoms and signs (including worsening of laboratory values; e.g., new or worsening hypercalcemia) that indicate unequivocal progression of disease, * No decline in ECOG Performance Status (PS) that can be attributed to disease progression.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
455
HDM201 120mg, Every 3 weeks, Per os
Ribociclib 200mg/day, once daily 2 weeks on/1 week off, Per os
Cabozantinib, 60 mg /day, continuous, Per os
Alectinib, 600mg twice daily, Per os
Regorafenib 160mg, once daily, 3 weeks on/1 week off, Per os
Trametinib 2 mg/day, continuous, Per os
Dabrafenib 150 mg twice daily, Per os
300 mg/day,continuous, Per os
Institut Bergonié
Bordeaux, France
RECRUITINGCentre François Baclesse
Caen, France
RECRUITINGCentre Léon Bérard
Lyon, France
RECRUITINGInstitut Paoli Calmettes
Marseille, France
RECRUITINGCentre Antoine LACASSAGNE
Nice, France
RECRUITINGInstitut Curie
Paris, France
NOT_YET_RECRUITINGInstitut de Cancérologie de Strasbourg
Strasbourg, France
RECRUITINGCHU Strasbourg - Hôpital de Hautepierre
Strasbourg, France
NOT_YET_RECRUITINGInstitut Claudius Regaud
Toulouse, France
RECRUITINGInstitut Gustave Roussy
Villejuif, France
RECRUITINGProgression free rate after 3 months (12 weeks) of treatment
The proportion of patients with a complete response (CR), a partial response (PR) or a stable disease (SD) at 3 months (12 weeks).
Time frame: 3 months (12 weeks)
Objective response rate after 3 months (12 weeks) of treatment
The proportion of patients with a complete or a partial response (CR or PR) as best overall response at 3 months (12 weeks).
Time frame: 3 months (12 weeks)
Duration of Response
Duration of response applies only to patients whose best overall response was a complete response or a partial response (CR or PR). It will be defined as the time from the date of first documented response (CR or PR) to the date of the first documented progression or death due to underlying cancer and censored at the date of the last adequate tumor assessment.
Time frame: Up to 3 years
Progression Free Survival
The time from the date of the first study drug administration to the first documented progression according to investigator assessment of RECIST version 1.1 or death due to any cause
Time frame: Up to 3 years
Overall survival
The time from the date of the first study drug administration to the date of death due to any cause
Time frame: Up to 3 years
Percentage of long-term responders (> 6 months)
The proportion of long term responders (\> 6 months)
Time frame: 6 months
Adverse Events
Nature, frequency and severity of Adverse Events (AEs), Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs) graded using Common Terminology Criteria for Adverse Events (CTCAE) V5.0.
Time frame: Up to 3 years
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