LB-100 (PP2A Inhibitor) and Atezolizumab (PD-L1 Inhibitor) in Metastatic Colorectal Cancer Patients

NCT06012734 | Recruiting Phase 1

• 1 other identifier: N22CLB
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase Ib trial studies the side effects and best dose of LB-100 when given with atezolizumab for the treatment of patients with metastatic microsatellite stable colorectal cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of the tumor to grow and spread. LB-100 has been shown to make anticancer drugs work better at killing cancer. LB-100 blocks a protein on the surface of cells called PP2A. Blocking this protein increases the stress signals for the tumor cells that express PP2A. Giving atezolizumab in combination with LB-100 may work better to treat metastatic colorectal cancer patients as the cancer cells that experience increased stress signals are more susceptible for the immunotherapy.

Conditions

Metastatic Microsatellite-stable Colorectal Cancer

Keywords

Gastrointestinal Neoplasms; Colorectal cancer; Metastatic colorectal cancer; Microsatellite stable; Immune checkpoint inhibitors

Outcome Measures

Primary Outcomes (1)

• The RP2D of LB-100 when given in combination with standard doses of atezolizumab

  up to 2 years

Secondary Outcomes (11)

• Disease control rate

  6 months

• Objective response rate

  6 months

• Duration of overall response

  up to 2 years

• Progression free survival

  up to 2 years

• Overall survival

  Assessed up to 2 years

Other Outcomes (3)

• Serine/threonine hyperphosphorylation in peripheral white blood cells

  Blood sample cycle 1 day 1. Each cycle is 21 days.

• Mismatch repair deficiency status

  Before start of treatment and one on treatment biopsy at Cycle 3 day 3. Each cycle is 21 days

• Concentration of LB-100 and endothall in tumor tissue

  On treatment biopsy at Cycle 3 day 3. Each cycle is 21 days

Study Arms (1)

LB-100 plus atezolizumab

EXPERIMENTAL

LB-100 IV over 15 minutes on day 1 and day 3 Atezolizumab IV over 30-60 minutes on day 1 Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity

Drug: LB-100; Drug: Atezolizumab

Interventions

LB-100 DRUG

IV on day 1 and day 3

Also known as: PP2A inhibitor LB-100

LB-100 plus atezolizumab

Atezolizumab DRUG

IV on day 1

Also known as: Tecentriq

LB-100 plus atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form (ICF);
• Age ≥ 18 years at time of signing ICF;
• Ability to comply with the study protocol;
• Histological or cytological confirmed colorectal cancer;
• Immunohistochemically confirmation of microsatellite stable (MSS) phenotype;
• Disease progression during treatment with standard of care;
• 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;
• Able and willing to undergo blood sampling and tumour biopsies at baseline, if no adequate archival material is available, and during therapy;
• Availability of representative tumor specimen for exploratory biomarker research;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Life expectancy of at least 3 months;
• Negative HIV test at screening. Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/µL, and have an undetectable viral load;
• Negative hepatitis B test at screening;
• Negative hepatitis C virus test at screening;
• Adequate hematologic and end-organ function as defined by:

You may not qualify if:

• Unable to follow study procedures;
• Patients using prohibited medication;
• Any unresolved grade ≥ 2 toxicities related to prior treatments (excluding alopecia) according to CTCAE version 5.0;
• 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 history 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;
• History of leptomeningeal disease;
• Uncontrolled tumor-related pain. Patients requiring pain medication must be on a sta-ble regimen at study entry;
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. Patients with indwelling catheters are allowed;
• Uncontrolled symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \>12 mg/dL, or corrected calcium greater than ULN);
• Active or history of auto-immune disease or immune deficiency;
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field is permitted;

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (1)

Antoni van Leeuwenhoek

Amsterdam, North Holland, 1066CX, Netherlands

RECRUITING

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Colorectal Neoplasms

Interventions

LB100; atezolizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Neeltje Steeghs, MD, PhD

  The Netherlands Cancer Institute - Antoni van Leeuwenhoek

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Merel Lucassen, MD

CONTACT

+31205129111; me.lucassen@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2023
• First Posted: August 25, 2023
• Study Start: June 18, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 30, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)