Clinical trial NCT03422679: Study of CB-103 in Adult Patients With Advanced or Metastatic Solid Tumours and Haematological Malignancies
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 Locally Advanced or Metastatic Solid Tumours and Haematological Malignancies Characterised by Alterations of the NOTCH Signalling Pathway
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Colorectal Cancer
Adenoid Cystic Carcinoma
Non-hodgkin Lymphoma
Glomus Tumor, Malignant
Hepatocellular Carcinoma
Osteosarcoma
T-ALL
Keywords: advanced solid tumours
haematological malignancies
phase I/II
NOTCH pathway
pan-NOTCH inhibitor
Lead sponsor: Cellestia Biotech AG
Sponsor class: INDUSTRY
First posted: 2018-02-06
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This Phase I/IIA, open label, multicenter, dose escalation study of CB-103 in patients with Locally 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 (Phase I) 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 in treatment cycles of 28-days each. Aim of the expansion Phase IIA, Part B of the study will be to collect preliminary evidence of anti-tumour activity.

Eligibility criteria: INCLUSION CRITERIA:

1. Disease

   * Patients with histologically or cytologically confirmed solid tumours (breast cancer (triple negative breast cancer \[TNBC\], ER+/-, HER2+/-), gastrointestinal (GI) cancers (resistant to oxaliplatin or irinotecan-based therapy colorectal cancer \[CRC\]), osteosarcoma, adenoid cystic carcinoma (ACC), and malignant glomus tumour) that are surgically unresectable, locally advanced, or metastatic and whose disease has progressed on at least one line of systemic therapy (with the exception of ACC patients who are allowed to be systemic treatment-naïve) and for whom no established therapeutic alternatives exist. Any other solid cancer (including lymphoma) with a confirmed NOTCH1-4 activating mutation or genetic lesion.
   * Relapsed or refractory (r/r) T-cell acute lymphoblastic leukaemia (T-ALL) or lymphoma (T-LBL) with a confirmed NOTCH pathway activation. Refractory patients are defined as T-ALL/T-LBL patients with ≥ 5% bone marrow blasts, and/or concomitant extramedullary involvement, who have not achieved a CR after standard induction/consolidation therapy attempt.
2. Demography: men and women ≥ 18 years old
3. Adequate organ function and laboratory results
4. Adequate contraceptive measures
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

   * In patients with solid tumours cytotoxic chemotherapy within 3 weeks
   * In T-ALL/T-LBL patients, prior anticancer therapy less than 2 weeks prior to starting therapy or 5 half-lives (whichever is longer) with exceptions.
   * 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.

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: 28 days
Secondary outcomes:
measure: Overall Response Rate
timeFrame: 24 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Lyon
country: France
facility: Centre Hospitalier Lyon-Sud
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Berlin
country: Germany
facility: Charite- Universitaetsmedizin Berlin- Campus Benjamin Franklin
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen Heidelberg
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital - Yonsei Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Barcelona
country: Spain
facility: Hospital Quirón Barcelona
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology (VHIO)
city: Barcelona
country: Spain
facility: Catalan Institute of Oncology
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Southern Switzerland
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St.Gallen
Study officials:
affiliation: Vall d'Hebron University Hospital
name: Elena Garalda, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hanna GJ, Stathis A, Lopez-Miranda E, Racca F, Quon D, Leyvraz S, Hess D, Keam B, Rodon J, Ahn MJ, Kim HR, Schneeweiss A, Ribera JM, DeAngelo D, Perez Garcia JM, Cortes J, Schonborn-Kellenberger O, Weber D, Pisa P, Bauer M, Beni L, Bobadilla M, Lehal R, Vigolo M, Vogl FD, Garralda E. A Phase I Study of the Pan-Notch Inhibitor CB-103 for Patients with Advanced Adenoid Cystic Carcinoma and Other Tumors. Cancer Res Commun. 2023 Sep 14;3(9):1853-1861. doi: 10.1158/2767-9764.CRC-23-0333.