A Study Investigating the Efficacy and Safety of Alcestobart (LBL-007) Plus Tislelizumab in Combination With Bevacizumab Plus Fluoropyrimidine Versus Bevacizumab Plus Fluoropyrimidine in Participants With Unresectable or Metastatic Colorectal Cancer

Phase 2Active Not RecruitingNCT05609370

BeiGene113 enrolled

Overview

This is a Phase 1b/2 study to investigate the efficacy and safety of alcestobart (LBL-007) plus tislelizumab when administered in combination with bevacizumab plus fluoropyrimidine, and alcestobart in combination with bevacizumab plus fluoropyrimidine versus bevacizumab plus fluoropyrimidine to participants with colorectal cancer.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

113

Conditions

Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer

Interventions

Alcestobart

Administered intravenously (IV) at one of the following doses * Low dose: 150 mg once every 3 weeks * Medium dose: 300 mg once every 3 weeks or 200 mg once every 2 weeks * High dose: 600 mg once every 3 weeks or 400 mg once every 2 weeks

Fluoropyrimidine (FP)DRUG

Fluoropyrimidine treatment included one of the following: \- Capecitabine 850 mg/m\^2 administered orally twice daily for the first 2 weeks of each 3-week cycle, OR \- 5-fluorouracil (5-FU) 1600 to 2400 mg/m\^2 continuous infusion over 46 to 48 hours in combination with leucovorin or levoleucovorin (LV) IV administered per local guidelines and/or prescribing information once every 2 weeks.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participant must have measurable disease as defined per RECIST((Response Evaluation Criteria in Solid Tumors) version 1.1 * Has a histologically confirmed colorectal adenocarcinoma with metastatic or unresectable disease (Stage IV as defined by American Joint Committee on Cancer \[AJCC\] 8th edition) * No prior systemic therapy for colorectal cancer (CRC) in the metastatic setting except for the induction treatment of first-line therapy. Note: Local regional treatment performed during induction systemic treatment is allowed * Participants who have completed the first-line induction treatment, with an overall response of stable disease or better. The duration of induction treatment should be completed within approximately 6 months. The first dose of study treatment needs to occur within 2 weeks (for 2-week regimen) or 3 weeks (for 3-week regimen) to 6 weeks after Day 1 of the last cycle of induction therapy Exclusion Criteria: * Participants whose disease has become resectable at the investigator's discretion during or after induction treatment are not eligible * Progressive disease occurred less than 6 months from completion of any prior neoadjuvant therapy (ie, chemotherapy with or without radiotherapy) or adjuvant therapy (ie, chemotherapy with or without radiotherapy), whichever occurred later * Participants who have been treated with anti-epidermal growth factor receptor (EGFR) antibody in the induction treatment * Any prior therapy targeting T-cell stimulation or checkpoint pathways * Participants with B-raf proto-oncogene, serine/threonine kinase (BRAF)V600E mutations * Have locally or centrally confirmed microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR) method or dMMR by immunohistochemistry (IHC) method Note: Other protocol defined criteria may apply.

Locations (64)

Alaska Oncology and Hematology, Llc

Anchorage, Alaska, United States

Banner Md Anderson Cancer Center

Gilbert, Arizona, United States

Helios Clinical Research

Cerritos, California, United States

Valkyrie Clinical Trials

Los Angeles, California, United States

Usc Norris Comprehensive Cancer Center (Nccc)

Los Angeles, California, United States

Outcomes

Primary Outcomes

Phase 1b: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatments, whether considered related to study treatments or not. A serious AE (SAE) was any untoward medical occurrence that, at any dose- * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.

Time frame: From first dose of study drug up to 30 days after last dose; maximum time on treatment was 16.2 months.

Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Positive Arms A and C

PFS, as assessed by the investigator per RECIST v1.1 is defined as the time from the date of randomization to the date of first documentation of disease progression or death, whichever occured first.

Time frame: From randomization until disease progression, death, study discontinuation, or data cutoff, whichever occurred first (maximum follow-up time: Arm A, 11.0 months, Arm C, 8.0 months)

Secondary Outcomes

Phase 2: Objective Response Rate (ORR) as Assessed by The Investigator in PD-L1 Positive Arms A and C

ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) from the time of randomization. CR and PR were confirmed per RECIST v1.1. * CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. * PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time frame: From randomization until disease progression, death, study discontinuation, or data cutoff, whichever occurred first (maximum follow-up time: Arm A, 11.0 months, Arm C, 8.0 months)

Phase 2: Duration of Response (DOR) as Assessed by The Investigator in PD-L1 Positive Arms A and C

DOR is defined as the time from the first determination of an objective confirmed response after randomization until the first documentation of disease progression or death, whichever comes first.

Time frame: From first documented response until disease progression or death (maximum follow-up time for DOR was 4.2 months)

Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Negative Arms D and E

PFS, as assessed by the investigator per RECIST v1.1 is defined as the time from the date of randomization to the date of first documentation of disease progression or death, whichever occurs first.

Time frame: From randomization until disease progression, death, study discontinuation, or data cutoff, whichever occurred first (maximum follow-up time: Arm D, 10.6 months, Arm E, 10.5 months)

Phase 2: Objective Response Rate (ORR) as Assessed by The Investigator in PD-L1 Negative Arms D and E

ORR is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) from the time of randomization. CR and PR were confirmed per RECIST v1.1. * CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. * PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time frame: From randomization until disease progression, death, study discontinuation, or data cutoff, whichever occurred first (maximum follow-up time: Arm D, 10.6 months, Arm E, 10.5 months))

Phase 2: Duration of Response (DOR) as Assessed by The Investigator in PD-L1 Negative Arms D and E

DOR, defined as the time from the first confirmed objective response after randomization until the first documentation of disease progression or death, whichever comes first.

Time frame: From first documented response until disease progression or death (maximum follow-up time for DOR was 2.8 months)

Phase 2: Number of Participants With Treatment-emergent AEs and SAEs

Time frame: From first dose of study drug up to 30 days after last dose; maximum time on treatment in Phase 2 was 10.9 months