Clinical trial NCT04468607: A Study of BLYG8824A in Participants With Locally Advanced or Metastatic Colorectal Cancer
Official title: A Phase I, Open-Label, Dose-Escalation Study Of The Safety And Pharmacokinetics Of BLYG8824A Administered Intravenously In Patients With Locally Advanced Or Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-13
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, and pharmacokinetics of BLYG8824A and will make a preliminary assessment of the anti-tumor activity of BLYG8824A in patients with locally advanced or metastatic colorectal cancer.


Eligibility criteria: Inclusion Criteria:

* ECOG performance status of 0 or 1
* Life expectancy of at least 12 weeks
* Histologically or cytologically documented invasive CRC: incurable, unresectable, locally advanced or metastatic CRC previously treated with multimodality therapy or mCRC
* Locally advanced or metastatic CRC that has relapsed or is refractory to established therapies
* Prior disease progression (or intolerance) following oxaliplatin, irinotecan, fluoropyrimidines, and anti-EGFR monoclonal antibodies
* An archival tissue specimen or fresh baseline biopsy (when archival is not available) is required for enrollment into the study
* Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Non-measurable evaluable disease is acceptable for dose-escalation.
* Adequate hematologic and end organ function
* Acute, clinically significant treatment-related toxicity from prior therapy resolved to Grade ≤ 1 prior to study entry

Expansion Cohort-Specific Inclusion Criteria

* MSS or MSI-L disease as determined by polymerase chain reaction (PCR) and/or IHC
* Measurable disease by RECIST v1.1 with at least one measurable target lesion in the expansion cohort
* Progression must have occurred during or after most recent treatment for locally advanced or metastatic colorectal cancer
* For patients enrolled in either a dedicated biopsy cohort or other expansion cohorts where biopsy is clinically feasible, willingness to consent to mandatory fresh pretreatment and on-treatment biopsies of safely accessible tumor lesions

Exclusion Criteria:

* Pregnant or breastfeeding, or intending to become pregnant during the study or within 4 months after the final dose of BLYG8824A
* Significant cardiopulmonary dysfunction
* Known clinically significant liver disease
* Positive serologic or PCR test results for acute or chronic HBV infection
* Acute or chronic HCV infection
* HIV seropositivity
* Poorly controlled Type 2 diabetes mellitus
* Current treatment with medications that are well known to prolong the QT interval
* Primary CNS malignancy, untreated CNS metastases, or active CNS metastases
* Leptomeningeal disease
* Spinal cord compression that has not been definitively treated with surgery and/or radiation
* History of autoimmune disease
* Prior allogeneic stem cell or solid organ transplantation

Primary outcomes:
measure: Incidence and Nature of DLTs
timeFrame: Approximately 48 months
measure: Number of Patricipants with Adverse Events
timeFrame: Approximately 48 months
measure: Number Of Cycles Received
timeFrame: Approximately 48 months
measure: Dose Intensity
timeFrame: Approximately 48 months
measure: Maximum Tolerated Dose(s) MTD(s) of BLYG8824A
timeFrame: Approximately 48 months
Secondary outcomes:
measure: Serum Concentration of BLYG8824A
timeFrame: At predifined interevals from Cycle 1 Day 1; Cycle 2 Day 1; Cycles ≥ 3, Day 1; Treatment Completion/ Discontinuation (Cycle length: 21 days)
measure: Overall Response Rate (ORR)
timeFrame: Approximately 48 months
measure: Duration of Response (DOR)
timeFrame: Approximately 48 months
measure: Presence of Anti-drug Antibodies (ADAs)
timeFrame: Cycle 1, Day 1; Cycle 2 Day 1; Cycles ≥ 3, Day 1; Treatment Completion/ Discontinuation (Cycle length: 21 days)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Madrid
country: Spain
facility: START Madrid-FJD, Hospital Fundacion Jimenez Diaz
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: