Patient case: 64-year-old male with gastric cancer; genetic feature: ERBB2 amplification

Clinical trial: Study of CB-103 in Adult Patients With Advanced or Metastatic Solid Tumours and Haematological Malignancies

Summary: This is a phase I/II, non randomized, open-label, dose escalation study to investigate the safety, tolerability and preliminary efficacy of CB-103.

Detailed description: This Phase I/IIA, open label, multicenter, dose escalation study of CB-103 in patients with Advanced or Metastatic Solid Tumours and Haematological Malignancies. After providing signed informed consent, patients will be screened for entry into the study. The study will be conducted in 2 stages: dose escalation in Part A of the study followed by dose expansion in Part B (Phase IIA).
  Escalation cohorts will receive repeat doses of CB-103 to determine the MTD and RP2D.
  CB-103 will be administered orally on a once-daily schedule, based on a 28-day treatment cycle. Aim of the expansion Phase IIA, Part B of the study will be to collect preliminary evidence of anti-tumour activity.

Eligibility: INCLUSION CRITERIA:
  1. Disease
  -  Patients with histologically or cytologically confirmed solid tumours that are surgically unresectable, locally advanced, or metastatic and whose disease has progressed on at least one line of systemic therapy and for whom no standard curative therapy exists.
  -  The following solid tumour indications are allowed to be enrolled into Part A of this study (dose escalation) based on known involvement of the NOTCH pathway activation in these indications: Breast cancer (triple negative breast cancer [TNBC], ER+/-, HER2+/-), gastrointestinal (GI) cancers (colorectal cancer [CRC], cholangiocellular carcinoma [CCC]), sarcomas (osteosarcoma, liposarcoma, rhabdomyosarcoma, fibrosarcoma), desmoid tumours, adenoid cystic carcinoma, and malignant glomus tumour.
  -  Patients with histologically or cytologically confirmed, advanced haematological malignancies) whose disease has relapsed or progressed upon standard therapy and for whom at that point no standard therapy exists: Non-Hodgkin lymphomas (NHL): Follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, marginal zone B cell lymphoma (MZCL), splenic marginal zone lymphoma (SMZL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL), anaplastic large cell lymphoma (ALCL).
  2. Demography Men and women ≥ 18 years old on the day of signing informed consent.
  3. Organ function and laboratory results
  Patients must have the following laboratory values:
  a.ANC ≥ 1.5x10^9/L (solid tumour indications) or ≥ 1.0x10^9/L (haematological malignancies) b.Haemoglobin (Hgb) ≥ 10 g/dL (≥ 100 g/L) c.Platelet count ≥ 75 x 109/L (no platelet transfusion or growth factor support in the preceding 7d) d.Total serum bilirubin ≤ 1.5xULN e.ALP ≤ 2.5xULN (if abnormalities are due to the underlying malignancy and known bone metastases, then ALP must be ≤ 5xULN) f.AST/SGOT and ALT/SGPT ≤ 2.5xULN (if abnormalities are due to the underlying malignancy and known hepatic metastases, AST and ALT must be ≤ 5xULN) g.Serum creatinine ≤ 1.5xULN (if serum creatinine > 1.5xULN, then serum creatinine clearance (CrCl) ≥ 50 mL/min h to k: Potassium, Total calcium (corrected for serum albumin), Magnesium and Phosphorus levels: within normal limits or correctable with supplements l.Serum albumin concentration ≥ 30 g/L m.Serum amylase and serum lipase ≤ ULN n.PTT ≤ 1.5 x ULN and INR ≤ 1.3 (unless receiving therapeutic anticoagulants)
  4. Contraceptive measures
  -  Women of childbearing potential and men must agree to use at least two highly effective forms of contraception throughout the entire clinical trial period and for 90d post-treatment completion.
  -  Men whose partners could be of childbearing potential must routinely use a condom throughout the clinical trial period and for 90d posttreatment completion. The partner should also use a reliable form of contraception.
  5. Signed informed consent
  EXCLUSION CRITERIA
  1. Medical History
  1. Patients with symptomatic CNS metastases (neurologically unstable or requiring increasing doses of steroids to control their CNS disease)
  2. Hypersensitivity to any of the excipients of CB-103
  3. Patients with unresolved nausea, vomiting, or diarrhoea of CTCAE grade > 1
  4. Impairment of GI function or presence of GI disease that may significantly alter the absorption of CB-103
  5. History of second or other primary cancer with the exception of:
  -  Curatively treated non-melanomatous skin cancer
  -  Curatively treated cervical cancer or breast carcinoma in situ
  -  Other primary solid tumour treated with curative intent and no known active disease present and no treatment administered during the last 2 years.
  2. Exclusionary concurrent medical conditions Impaired cardiac function or clinically significant cardiac diseases.
  3. Prior Therapy
  -  Cytotoxic chemotherapy within 3 weeks
  -  Any investigational treatment (including NOTCH signaling inhibitors and prior treatment with CB-103) within 4 weeks of scheduled CB-103 dosing day 1
  -  Concurrent enrolment in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo
  -  Radiation therapy within 2 weeks of scheduled CB-103 dosing day 1
  -  Immunotherapy, biological therapies, targeted small molecules, hormonal therapies within 3 weeks of scheduled CB-103 dosing day 1
  -  Unresolved toxicity CTCAE grade > 1 from previous anti-cancer therapy or radiotherapy (excluding neurotoxicity, alopecia, ototoxicity, lymphopenia), or incomplete recovery from previous surgery.
  4. Current medications
  -  Drugs which prolong QT interval
  -  Acid reducing agents
  -  Patients receiving warfarin and phenytoin that cannot be discontinued at least one week prior to start of treatment with CB-103 and for the duration of the study
  -  Anticoagulants.
  5. Demography
  - Patients who are pregnant or breast feeding.
  6. Others - Patients who are unable or unwilling to comply with all study requirements for clinical visits, examinations, tests, and procedures.

Relevance to patient case: not relevant