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

NCT ID: NCT03422679

Last Updated: 2024-01-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-05
• Study Completion Date: 2022-11-11

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.

Conditions

Breast Cancer; Colorectal Cancer; Adenoid Cystic Carcinoma; Non-hodgkin Lymphoma; Glomus Tumor, Malignant; Hepatocellular Carcinoma; Osteosarcoma; T-ALL

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CB-103

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

Group Type: EXPERIMENTAL

CB-103

Intervention Type: DRUG

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

Interventions

CB-103

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cellestia Biotech AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elena Garalda, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vall d'Hebron University Hospital

Locations

Sarcoma Oncology Research Center

Santa Monica, California, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

MD Anderson

Houston, Texas, United States

Centre Hospitalier Lyon-Sud

Lyon, , France

Hôpital Saint-Louis

Paris, , France

Charite- Universitaetsmedizin Berlin- Campus Benjamin Franklin

Berlin, , Germany

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Nationales Centrum für Tumorerkrankungen Heidelberg

Heidelberg, , Germany

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital - Yonsei Cancer Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Hospital Quirón Barcelona

Barcelona, , Spain

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, , Spain

Catalan Institute of Oncology

Barcelona, , Spain

Hospital Ramón y Cajal

Madrid, , Spain

Oncology Institute of Southern Switzerland

Bellinzona, , Switzerland

Kantonsspital St.Gallen

Sankt Gallen, , Switzerland

Countries

United States; France; Germany; South Korea; Spain; Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 37712875 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39563886 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CB103-C-101

Identifier Type: -

Identifier Source: org_study_id