FindTrial
Sign In

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

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

Status
Terminated
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03422679
Enrollment
79
Registered
2018-02-06
Start date
2017-12-05
Completion date
2022-11-11
Last updated
2024-01-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

advanced solid tumours, haematological malignancies, phase I/II, NOTCH pathway, pan-NOTCH inhibitor

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.

Interventions

DRUGCB-103

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

Sponsors

Cellestia Biotech AG
Lead SponsorINDUSTRY

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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.

Design outcomes

Primary

MeasureTime frameDescription
Dose Limiting Toxicity (DLT)28 daysNumber 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).

Secondary

MeasureTime frameDescription
Overall Response Rate24 monthsNumber of patients with an overall response rate (CR+PR assessed by RECSIT v1.1 or CR or CRi by NCCN guidelines) up to 24 months

Countries

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

Participant flow

Participants by arm

ArmCount
Cohort 1
CB-103 13mg once daily
5
Cohort 2
CB-103 26mg once daily
3
Cohort 3
CB-103 52mg once daily
7
Cohort 4
CB-103 104mg once daily
7
Cohort 5
CB-103 148mg once daily
3
Cohort 6
CB-103 217mg once daily
4
Cohort 7
CB-103 348mg once daily
3
Cohort 8
CB-103 522mg once daily
9
Cohort 9
CB-103 250mg twice daily
5
Cohort 10
CB-103 300mg twice daily, 5 days on, 2 days off
6
Cohort 11
CB-103 400mg twice daily, 5 days on, 2 days off
4
Cohort 12
CB-103 500mg twice daily, 5 days on, 2 days off
8
Confirmatory Cohort
CB-103 500mg once daily
15
Total79

Baseline characteristics

CharacteristicCohort 2Cohort 3Cohort 4Cohort 5Cohort 6Cohort 7Cohort 8Cohort 9Cohort 10Cohort 11Cohort 1Cohort 12Confirmatory CohortTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants3 Participants2 Participants0 Participants1 Participants1 Participants4 Participants2 Participants1 Participants1 Participants2 Participants4 Participants3 Participants24 Participants
Age, Categorical
Between 18 and 65 years
3 Participants4 Participants5 Participants3 Participants3 Participants2 Participants5 Participants3 Participants5 Participants3 Participants3 Participants4 Participants12 Participants55 Participants
Age, Continuous55.7 years52.7 years54.4 years51.3 years54.8 years61.7 years56.6 years64.6 years54 years51.5 years57.2 years58.6 years46.9 years54.4 years
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants6 Participants7 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
White
3 Participants7 Participants7 Participants2 Participants4 Participants3 Participants9 Participants4 Participants6 Participants4 Participants5 Participants7 Participants9 Participants70 Participants
Region of Enrollment
Germany
0 participants0 participants0 participants0 participants0 participants0 participants0 participants0 participants1 participants2 participants0 participants1 participants1 participants5 participants
Region of Enrollment
South Korea
0 participants0 participants0 participants0 participants0 participants0 participants0 participants0 participants0 participants0 participants0 participants0 participants9 participants9 participants
Region of Enrollment
Spain
1 participants4 participants4 participants3 participants4 participants2 participants5 participants3 participants3 participants0 participants4 participants2 participants2 participants37 participants
Region of Enrollment
Switzerland
2 participants3 participants3 participants0 participants0 participants1 participants4 participants1 participants0 participants0 participants1 participants0 participants0 participants15 participants
Region of Enrollment
United States
0 participants0 participants0 participants0 participants0 participants0 participants0 participants1 participants2 participants2 participants0 participants5 participants3 participants13 participants
Sex: Female, Male
Female
1 Participants3 Participants3 Participants3 Participants2 Participants2 Participants5 Participants2 Participants4 Participants1 Participants1 Participants2 Participants5 Participants34 Participants
Sex: Female, Male
Male
2 Participants4 Participants4 Participants0 Participants2 Participants1 Participants4 Participants3 Participants2 Participants3 Participants4 Participants6 Participants10 Participants45 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
EG007
affected / at risk
EG008
affected / at risk
EG009
affected / at risk
EG010
affected / at risk
EG011
affected / at risk
EG012
affected / at risk
deaths
Total, all-cause mortality
0 / 50 / 30 / 70 / 70 / 30 / 40 / 30 / 90 / 50 / 60 / 40 / 80 / 15
other
Total, other adverse events
3 / 52 / 35 / 74 / 72 / 33 / 43 / 37 / 94 / 56 / 64 / 47 / 89 / 15
serious
Total, serious adverse events
0 / 50 / 30 / 71 / 70 / 30 / 40 / 30 / 91 / 50 / 60 / 40 / 81 / 15

Outcome results

Primary

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).

Time frame: 28 days

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Cohort 1Dose Limiting Toxicity (DLT)0 Participants
Cohort 2Dose Limiting Toxicity (DLT)0 Participants
Cohort 3Dose Limiting Toxicity (DLT)0 Participants
Cohort 4Dose Limiting Toxicity (DLT)0 Participants
Cohort 5Dose Limiting Toxicity (DLT)0 Participants
Cohort 6Dose Limiting Toxicity (DLT)0 Participants
Cohort 7Dose Limiting Toxicity (DLT)0 Participants
Cohort 8Dose Limiting Toxicity (DLT)1 Participants
Cohort 9Dose Limiting Toxicity (DLT)0 Participants
Cohort 10Dose Limiting Toxicity (DLT)0 Participants
Cohort 11Dose Limiting Toxicity (DLT)1 Participants
Cohort 12Dose Limiting Toxicity (DLT)0 Participants
Confirmatory CohortDose Limiting Toxicity (DLT)0 Participants
Secondary

Overall Response Rate

Number of patients with an overall response rate (CR+PR assessed by RECSIT v1.1 or CR or CRi by NCCN guidelines) up to 24 months

Time frame: 24 months

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Cohort 1Overall Response Rate1 Participants
Cohort 2Overall Response Rate2 Participants
Cohort 3Overall Response Rate5 Participants
Cohort 4Overall Response Rate5 Participants
Cohort 5Overall Response Rate2 Participants
Cohort 6Overall Response Rate1 Participants
Cohort 7Overall Response Rate2 Participants
Cohort 8Overall Response Rate4 Participants
Cohort 9Overall Response Rate2 Participants
Cohort 10Overall Response Rate5 Participants
Cohort 11Overall Response Rate1 Participants
Cohort 12Overall Response Rate4 Participants
Confirmatory CohortOverall Response Rate3 Participants

Source: ClinicalTrials.gov · Data processed: Feb 24, 2026