A Study to Assess the Safety, Tolerability, Blood levels and Efficacy of oral test drug CB-103 in Adult Patients with certain types of cancer

Phase 1

Conditions: MedDRA version: 21.0Level: LLTClassification code 10049280Term: Solid tumourSystem Organ Class: 100000004864
MedDRA version: 21.1Level: LLTClassification code 10025236Term: Lymphoblastic lymphoma (Precursor B-lymphoblastic lymphoma/leukaemia)System Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]
ocally advanced or metastatic solid tumours and relapsed or refractory T-cell acute lymphoblastic leukaemia or T-cell lymphoblastic lymphoma that show Notch pathway activation.
MedDRA version: 21.1Level: LLTClassification code 10066105Term: T-cell lymphoblastic leukaemia acuteSystem Organ Class: 100000004864

Registration Number: EUCTR2017-001491-35-DE

Lead Sponsor: Cellestia Biotech AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 240

Inclusion Criteria

1. Disease
a. Histologically or cytologically confirmed solid tumours that are
surgically unresectable, locally advanced, or metastatic, which have
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
which no established therapeutic alternatives exist.

b. Relapsed or refractory (r/r) T-ALL or T-LBL. 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.
Relapsed patients are defined as T-ALL/T-LBL patients who have
recurrent disease, i.e. = 5% bone marrow blasts and/or
concomitant extramedullary relapse, after having achieved a prior CR.

[For all other disease related inclusion criteria refer to protocol]

2. Demography
a. Men and women = 18 years old on the day of signing informed
consent.
b. Eastern Cooperative Oncology Group (ECOG) performance status 0 or
1.
c. Patients able and willing to swallow capsules.

3. Organ function and laboratory results
Patients must have the following laboratory values (obtained within 14
days of enrolment):
a. Total serum bilirubin = 1.5 x upper limit of normal (ULN)
b. Alkaline phosphatase (ALP) = 2.5 x ULN; if liver function
abnormalities are due to the underlying malignancy and known bone
metastases, then ALP must be = 5 x ULN
c. Serum aspartate aminotransferase (AST/SGOT) and alanine
aminotransferase (ALT/SGPT) = 2.5 x ULN; if liver function
abnormalities are due to the underlying malignancy and known hepatic
metastases, then AST and ALT must be = 5 x ULN
d. Serum creatinine = 1.5 x ULN; or if serum creatinine > 1.5 x ULN, then
serum creatinine clearance (CrCl) = 50 mL/min (estimated by Cockcroft-
Gault formula)
e. Potassium levels within normal limits or correctable with supplements
f. Total calcium levels (corrected for serum albumin) within normal limits
or correctable with supplements
g. Magnesium levels within normal limits or correctable with
supplements
h. Phosphorus levels within normal limits or correctable with
supplements
i. Serum albumin concentration = 30 g/L
j. Patients with solid tumours must have:
• Absolute neutrophil count (ANC) = 1.5 x 109/L
• Haemoglobin (Hgb) = 10 g/dL (= 100 g/L)
• Platelet count = 75 x 109/L (without platelet transfusion or growth
factor support in the preceding 7 days)
• Partial thromboplastin time (PTT) = 1.5 x ULN and international
normalised ratio (INR) = 1.3 (unless the patient is receiving therapeutic
anticoagulants)

4. Contraceptive measures
a. Women of childbearing potential must have a serum pregnancy test
performed within a maximum of 7 days before start of study treatment,
and a negative result must be documented before start of study
treatment.
b. Women of childbearing potential and men must agree to use at least
two highly effective forms of contraception (i.e., two of the following –
oral contraception, injectable contraceptives, mechanical contraception
including a condom for the partner, or an intrauterine coil) and must
continue using them throughout the entire clinical trial period and for 90
days post-treatment completion (duration of 3 ovulatory cycles).
Contraception must start from the day of 1st administration of CB-103.
c. Men whose partners could be of childbearing potential must routinely
use a condom throughout the entire clinical trial period and for 90 days
post-treatment com

Exclusion Criteria

1.Medical History
a.Patients with symptomatic CNS metastases (neurologically unstable or requiring increasing doses of steroids to control their CNS disease)
b.Hypersensitivity to any of the excipients of CB-103
c.Patients with unresolved nausea, vomiting, or diarrhoea of CTCAE grade>1
d.Impairment of GI function or presence of GI disease that may significantly alter the absorption of CB-103
e.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
a.Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
1.Clinically significant cardiac disease including congestive heart failure (NYHA class III or IV),arrhythmia or conduction abnormality requiring medication, or cardiomyopathy
2.Clinically uncontrolled hypertension (systolic blood pressure =160 mmHg or diastolic blood pressure =100 mmHg)
3.Complete left bundle branch block
4.Right bundle branch block + left anterior hemiblock
5.Mandatory use of a cardiac pacemaker
6.Congenital long QT syndrome
7.History or presence of sustained or symptomatic ventricular
tachyarrhythmia
8.Presence of atrial fibrillation
9.Clinically significant resting bradycardia (<50 bpm)
10.Corrected QTcF > 450 ms for males and>470 ms for females at the screening ECG
11.QRS=110 ms
12.History of symptomatic congestive heart failure
13.LVEF<50%. History of absolute decrease in LVEF of=15 absolute %, or=10 absolute% and crossing from>LLN to14.Angina pectoris=6 months prior to starting CB-103
15.Acute myocardial infarction=6 months prior to startingCB-103
b.General conditions or other clinically significant diseases, including any one of the following:
1.Haemorrhagic, embolic, or thrombotic stroke within 6 months prior to the first planned CB-103 treatment
2.For patients with solid tumours: prior bone marrow/haematopoietic stem cell transplant
3.Known infection with HIV or hepatitis B or C requiring treatment
4.Any active infection requiring the use of parenteral anti-microbial agents or>Grade2
5.Non-malignant interstitial lung disease or pneumonitis
6.Dyspnoea of any cause requiring supplemental oxygen therapy and dyspnoea at rest due to complications of advanced malignancy and comorbidities
7.Significant traumatic injury or major surgery within 14d of scheduled dosing day 1
8.Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol

3.Prior Therapy
a. In patients with solid tumours, cytotoxic chemotherapy within 3 weeks (6 weeks for nitrosoureas and mitomycin C) of the scheduled first dose of CB-103 on day 1.
b.In T-ALL/T-LBL patients, prior anti-cancer therapy less than 2 weeks prior to starting therapy or 5 half-lives (whichever is longer) with the following exceptions:
1. Up to 5 days of glucocorticoids (10 mg/m2 dexamethasone or equivalent/day) in combination with up to 3 doses of cyclophosphamide (200 mg/m2/day) are allowed as standard prephase treatment up to 1 day before start of study treatment
2. Mercaptopurine may be dosed up to 5 days prior to first dose of CB103
3.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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