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

NCT03422679 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: CB103-C-101
• Study Type: interventional
• Target: 79
• Locations: 6 countries
• Sites: 17

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.

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

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  Number of patients with dose limiting toxicity during the first cycle. DLT is defined as a severe adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications, that occurs ≤ 28 days following the first dose of CB-103 (Cycle 1).

  28 days

Secondary Outcomes (1)

• Overall Response Rate

  24 months

Study Arms (1)

CB-103

EXPERIMENTAL

CB-103 capsules will be administered orally in treatment cycles of 28-days each.

Drug: CB-103

Interventions

CB-103 DRUG

Hard gelatine capsules taken orally during treatment period. Treatment cycle is 28 days.

CB-103

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Demography: men and women ≥ 18 years old
• Adequate organ function and laboratory results
• Adequate contraceptive measures
• Signed informed consent

You may not qualify if:

• Medical History
• Patients with symptomatic CNS metastases (neurologically unstable or requiring increasing doses of steroids to control their CNS disease)
• Hypersensitivity to any of the excipients of CB-103
• Patients with unresolved nausea, vomiting, or diarrhoea of CTCAE grade \> 1
• Impairment of GI function or presence of GI disease that may significantly alter the absorption of CB-103
• 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.
• 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.

Sponsors & Collaborators

• Cellestia Biotech AG: lead

Study Sites (17)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Centre Hospitalier Lyon-Sud

Lyon, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

Charite- Universitaetsmedizin Berlin- Campus Benjamin Franklin

Berlin, 10117, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Nationales Centrum für Tumorerkrankungen Heidelberg

Heidelberg, 69120, Germany

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital - Yonsei Cancer Center

Seoul, 03722, South Korea

Location

Seoul National University Hospital

Seoul, 06351, South Korea

Location

Hospital Quirón Barcelona

Barcelona, 08023, Spain

Location

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, 08035, Spain

Location

Catalan Institute of Oncology

Barcelona, 08916, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Oncology Institute of Southern Switzerland

Bellinzona, 6500, Switzerland

Location

Kantonsspital St.Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 37712875 BACKGROUND

• Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.

  PMID: 39563886 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Colorectal Neoplasms; Carcinoma, Adenoid Cystic; Lymphoma, Non-Hodgkin; Glomus Tumor; Carcinoma, Hepatocellular; Osteosarcoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Vascular Tissue; Liver Neoplasms; Liver Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Results Point of Contact

• Title: Maria Bobadilla, Chief Development Officer
• Organization: Cellestia Biotech AG

maria.bobadilla@cellestia.com

+41616332957

Study Officials

• Elena Garalda, MD, PhD

  Vall d'Hebron University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2018
• First Posted: February 6, 2018
• Study Start: December 5, 2017
• Primary Completion: November 11, 2022
• Study Completion: November 11, 2022
• Last Updated: January 16, 2024
• Results First Posted: January 16, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); ES (4); CH (2); KR (3); US (3); DE (3)