Phase Ib Study with the Combination of LB100 (PP2A Inhibitor) and Atezolizumab (PDL1 Inhibi-Tor) in Metastatic Colorectal Cancer Patients – The CoLBAt Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Aug 2024 → ongoing

Decision date (initial)

2024-05-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Hoffmann-La Roche Ltd

External identifiers

EU CT number

2023-505534-98-00

ClinicalTrials.gov

NCT06012734

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Therapy, Pharmacokinetic, Efficacy

To determine the RP2D of LB–100 when given in combination with standard doses of Atezolizumab in patients with metastatic MSS CRC.

Secondary objectives 3

1. 1. To characterize the safety and tolerability of LB–100 in combination with Atezolizumab, assessed by the incidence and severity of AEs, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)
2. 2. To characterise the pharmacokinetic (PK) profiles of Atezolizumab, LB–100 and its active metabolite endothall, measured by the serum concentrations at timepoints specified in protocol section 8.4.7.
3. 3. To determine the efficacy of LB–100 in combination with Atezolizumab, measured by disease control rate (DCR), objective response rate (ORR), progression free survival (PFS), overall survival (OS) and duration of response (DoR).

Conditions and MedDRA coding

Microsatellite stable colorectal cancer patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Histological or cytological confirmed CRC
2. Measurable disease per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1). Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion criteria 8

1. Symptomatic or actively progressing central nervous system (CNS) metastases. Asymptomatic patients with treated or untreated CNS lesions are eligible, provided that all of the following criteria are met: Measurable disease, per RECIST v1.1, must be present outside the CNS; The patient has no histology of intracranial haemorrhage or spinal cord haemorrhage; The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole−brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment; The patient has no ongoing requirement for corticosteroids as therapy for CNS disease; If the patient is receiving anti−convulsant therapy, the dose is considered stable.
2. Uncontrolled tumour−related pain. Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrolment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco−regional therapy, if appropriate, prior to enrolment.
3. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters are allowed.
4. Uncontrolled symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium >12 mg/dL, or corrected calcium greater than ULN).
5. Active or history of auto–immune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain−Barré syndrome, or multiple sclerosis (see Appendix 2 for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions: Patients with a history of autoimmune−related hypothyroidism who are on thyroid replacement hormone are eligible for the study; Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study; Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g. patients with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met: Rash must cover <10% of body surface area; Disease is well controlled at baseline and requires only low−potency topical corticosteroids; There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral cacineurin inhibitors, or high−potency or oral corticosteroids within the previous 12 months.
6. History of idiopatic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug−induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
7. Active tuberculosis.
8. Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The main study endpoint is to determine the RP2D of LB−100 when administered in combination with standard doses of Atezolizumab, by assessing the maximum tolerated dose and incidences of adverse events.

Secondary endpoints 3

1. The efficacy will be evaluated using the disease control rate, objective response rate, progression free survival, overall survival and duration of response.
2. A pharmacokinetic profile of Atezolizumab, LB−100 and the active metabolite endothall will be included by measuring plasma concentrations and determining the pharmacokinetic parameters (e.g. maximal plasma concentration, area under the curve, half–life).
3. Additionally, relevant pharmacodynamics biomarkers will be explored.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Principal investigator

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Principal investigator

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications