Neural Network-based Treatment Decision Support Tool in Patients With Refractory Solid Organ Malignancies

2.1. Hypothesis We hypothesize that DRUID analysis of patients' somatic mutational profile from NGS diagnostic platform can be used as a treatment decision support tool in patients with refractory cancer without targetable mutations. Using algorithm selected treatment from a panel of 60 drugs we predict an objective response rate (ORR) of ≥ 25%.

2.2. Primary Objectives

• To prospectively determine if DRUID selected therapy based on NGS diagnostic profile input can lead to objective responses in refractory solid organ malignancies.

2.3. Secondary Objectives

• To assess clinical benefit rate (complete response, partial response and stable disease for ≥ 24 weeks)
• To assess progression-free and overall survival of patients treated with DRUID-guided therapy

Inclusion criteria

Patients may be included in the study only if they meet all of the following criteria:

• Age ≥ 21 years.
• Histological or cytological diagnosis solid organ malignancy
• Available results of comprehensive NGS panel testing performed on either tumour tissue or blood-based assay. If results are from blood-based assay, test must have been performed in the metastatic setting.
• ECOG 0-2.
• At least 1 measurable tumour lesions based on RECIST 1.1 criteria
• Estimated life expectancy of at least 12 weeks.
• Has documented progressive disease from last line of therapy.
• Has received at least 2 lines of palliative systemic therapy with no available standard therapy:
• Adequate organ function including the following:

• Bone marrow:

• Absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Haemoglobin ≥ 8 x 109/L
• Hepatic:

• Bilirubin ≤ 1.5 x upper limit of normal (ULN),
• ALT or AST ≤ 2.5x ULN, (or ≤ 5 X with liver metastases)
• Renal:

• Creatinine ≤ 1.5x ULN
• Signed informed consent from patient or legal representative.
• Able to comply with study-related procedures.

Exclusion criteria

• Treatment within the last 30 days with any investigational drug.
• Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
• Major surgery within 28 days of study drug administration.
• Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
• Pregnancy.
• Breast feeding.
• Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
• Active bleeding disorder or bleeding site.
• Non-healing wound.
• Second primary malignancy that is clinically detectable at the time of consideration for study enrolment.
• Symptomatic brain metastasis.