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

• ClinicalTrials.gov Identifier: NCT03422679
• Recruitment Status: Terminated
• First Posted: February 6, 2018
• Results First Posted: January 16, 2024
• Last Update Posted: January 16, 2024
• Sponsor: Cellestia Biotech AG
• Information provided by (Responsible Party): Cellestia Biotech AG

Tracking Information

• First Submitted Date: January 19, 2018
• First Posted Date: February 6, 2018
• Results First Submitted Date: October 23, 2023
• Results First Posted Date: January 16, 2024
• Last Update Posted Date: January 16, 2024
• Actual Study Start Date: December 5, 2017
• Actual Primary Completion Date: November 11, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 12, 2024)

Dose Limiting Toxicity (DLT) [ Time Frame: 28 days ]

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).

Original Primary Outcome Measures (submitted: January 30, 2018)

• Part A: Dose limiting toxicity (DLT) [ Time Frame: 28 days ]
  Number of patients with dose limiting toxicity
• Part B: antitumour efficacy [ Time Frame: up to 12 months ]
  Best overall response rates of each tumor type using appropriate response Evaluation Criteria

Current Secondary Outcome Measures (submitted: January 12, 2024)

Overall Response Rate [ Time Frame: 24 months ]

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

Original Secondary Outcome Measures (submitted: January 30, 2018)

• Part A and B: incidence of all adverse events and serious adverse events (safety and tolerability) [ Time Frame: up to 12 months ]
  Number of participants with adverse events as a measure of safety and tolerability
• Part A and B: pharmacokinetic - Cmax [ Time Frame: cycle 1: days 1, 2, 3, 8, 9, 15 & 22; cycle 2: day 1, 15 (cycle duration: 28 days) ]
  Maximum plasma concentration
• Part A and B: pharmacokinetic - tmax [ Time Frame: cycle 1: days 1, 2, 3, 8, 9, 15 & 22; cycle 2: day 1, 15 (cycle duration: 28 days) ]
  Time to Cmax
• Part A and B: pharmacokinetic - AUC [ Time Frame: cycle 1: days 1, 2, 8 and 9 (cycle duration: 28 days) ]
  Area under the curve during 8 and 24 hours
• Part A and B: pharmacokinetic - t1/2 [ Time Frame: cycle 1: days 1, 2, 3, 8, 9, 15 & 22; cycle 2: day 1, 15 (cycle duration: 28 days) ]
  elimination half-life
• Part A: preliminary antitumour efficacy [ Time Frame: up to 6 months ]
  Overall response rates of each tumor type using appropriate response Evaluation Criteria

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

Drug: CB-103

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

Study Arms

Experimental: CB-103

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

Intervention: Drug: CB-103

• Publications *: 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 7, 2023): 79
• Original Estimated Enrollment (submitted: January 30, 2018): 165
• Actual Study Completion Date: November 11, 2022
• Actual Primary Completion Date: November 11, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Korea, Republic of, Spain, Switzerland, United States
• Removed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03422679
• Other Study ID Numbers: CB103-C-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cellestia Biotech AG
• Original Responsible Party: Same as current
• Current Study Sponsor: Cellestia Biotech AG
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Elena Garalda, MD, PhD; Vall d'Hebron University Hospital

• PRS Account: Cellestia Biotech AG
• Verification Date: January 2024