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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03422679
Recruitment Status : Recruiting
First Posted : February 6, 2018
Last Update Posted : February 6, 2018
Information provided by (Responsible Party):
Cellestia Biotech AG

Brief 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.

Condition or disease Intervention/treatment Phase
Advanced or Metastatic Solid Tumours Breast Cancer Colorectal Cancer Gastric Cancer Cholangiocellular Carcinoma Ovarian Cancer Cervical Cancer Prostate Cancer Melanoma Sarcoma NSCLC Desmoid Tumour Adenoid Cystic Carcinoma Glioblastoma Multiforme Hodgkin Lymphoma Non-hodgkin Lymphoma Multiple Myeloma Drug: CB-103 Phase 1 Phase 2

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. In a dose escalation stage, approximately 25 patients will be enrolled. Escalation cohorts of 3 to 6 patients will receive repeat doses of CB-103 to determine the MTD and RP2D. A Bayesian logistic regression model with overdose control is used.

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 and to confirm the safety of the CB-103 MTD/RP2D in different expansion arms consisting of up to 140 patients with pre-selected cancer indications with tumour cells characterised by NOTCH over-activation.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 165 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/IIA, Multi-Centre, Open-Label, Dose-Escalation Study With Expansion Arms to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CB-103 Administered Orally in Adult Patients With Advanced or Metastatic Solid Tumours and Haematological Malignancies Characterised by Alterations of the NOTCH Signalling Pathway
Actual Study Start Date : December 5, 2017
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 30, 2021

Arm Intervention/treatment
Experimental: CB-103
CB-103 capsules will be administered orally as a continuous once daily (QD) dosing during the treatment period of Part A (escalation) and Part B (expansion). The administration schedule may be adapted during dose escalation (e.g. twice-daily, intermittent dosing schedule) depending on the PK and safety signals that occur.
Drug: CB-103
Capsules, taken once daily during treatment period A and B. Treatment cycle is 28 days.Starting dose is 15 mg.

Primary Outcome Measures :
  1. Part A: Dose limiting toxicity (DLT) [ Time Frame: 28 days ]
    Number of patients with dose limiting toxicity

  2. Part B: antitumour efficacy [ Time Frame: up to 12 months ]
    Best overall response rates of each tumor type using appropriate response Evaluation Criteria

Secondary Outcome Measures :
  1. Part A and B: incidence of all adverse events and serious adverse events (safety and tolerability) [ Time Frame: up to 12 months ]
    Number of participants with adverse events as a measure of safety and tolerability

  2. Part A and B: pharmacokinetic - Cmax [ Time Frame: cycle 1: days 1, 2, 3, 8, 9, 15 & 22; cycle 2: day 1, 15 (cycle duration: 28 days) ]
    Maximum plasma concentration

  3. Part A and B: pharmacokinetic - tmax [ Time Frame: cycle 1: days 1, 2, 3, 8, 9, 15 & 22; cycle 2: day 1, 15 (cycle duration: 28 days) ]
    Time to Cmax

  4. Part A and B: pharmacokinetic - AUC [ Time Frame: cycle 1: days 1, 2, 8 and 9 (cycle duration: 28 days) ]
    Area under the curve during 8 and 24 hours

  5. Part A and B: pharmacokinetic - t1/2 [ Time Frame: cycle 1: days 1, 2, 3, 8, 9, 15 & 22; cycle 2: day 1, 15 (cycle duration: 28 days) ]
    elimination half-life

  6. Part A: preliminary antitumour efficacy [ Time Frame: up to 6 months ]
    Overall response rates of each tumor type using appropriate response Evaluation Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  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, cholangiocellular carcinoma [CCC], gastric cancer), ovarian cancer, cervical cancer, prostate cancer, non-small cell lung cancer (NSCLC; lung adeno-ca), melanoma, sarcomas (osteosarcoma, liposarcoma, rhabdomyosarcoma, fibrosarcoma), desmoid tumours, adenoid cystic carcinoma, and GBM.

    • 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:

      • Hodgkin lymphoma (HL)
      • 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), central nervous system (CNS) lymphoma
      • Multiple myeloma (MM).
  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, 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) f.Serum creatinine ≤ 1.5xULN (if serum creatinine > 1.5xULN, then serum creatinine clearance (CrCl) ≥ 50 mL/min g to j: Potassium, Total calcium (corrected for serum albumin), Magnesium and Phosphorus levels: within normal limits or correctable with supplements k.Serum albumin concentration ≥ 30 g/L l.Serum amylase and serum lipase ≤ ULN m.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


  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
    • Prior treatment with any NOTCH signalling inhibitor compound
    • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03422679

Contact: Dirk Weber, MD +41 79 9441580

Academic Medical Center Not yet recruiting
Amsterdam, Netherlands, 1105 AZ
Maastricht UMC Not yet recruiting
Maastricht, Netherlands, 6202 AZ
UMC Utrecht Cancer Center Not yet recruiting
Utrecht, Netherlands, 3508 GA
Instituto Oncológico Baselga. IOB Not yet recruiting
Barcelona, Spain, 08023
Vall d'Hebron Institute of Oncology (VHIO) Recruiting
Barcelona, Spain, 08035
Hospital Ramón y Cajal Recruiting
Madrid, Spain, 28034
Oncology Institute of Southern Switzerland Recruiting
Bellinzona, Switzerland, 6500
Sponsors and Collaborators
Cellestia Biotech AG

Responsible Party: Cellestia Biotech AG Identifier: NCT03422679     History of Changes
Other Study ID Numbers: CB103-C-101
First Posted: February 6, 2018    Key Record Dates
Last Update Posted: February 6, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Cellestia Biotech AG:
advanced solid tumours
haematological malignancies
phase I/II
NOTCH pathway
pan-NOTCH inhibitor

Additional relevant MeSH terms:
Colorectal Neoplasms
Stomach Neoplasms
Uterine Cervical Neoplasms
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms, Plasma Cell
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Multiple Myeloma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Carcinoma, Adenoid Cystic
Fibromatosis, Aggressive