Clinical trial NCT03697304: Platform Trial Evaluating Safety and Efficacy of BI 754091 Anti- PD-1 Based Combination Therapies in PD-(L)1 naïve and PD- (L)1 Pretreated Patient Populations With Advanced/Metastatic Solid Tumours
Official title: An Open-label, Phase II, Platform Trial Evaluating Safety and Efficacy of Multiple BI 754091 (Ezabenlimab) Anti-PD-1 Based Combination Regimens in PD-(L)1 naïve and PD-(L)1 Pretreated Patient Populations With Advanced and/or Metastatic Solid Tumours Who Have Had at Least One Line of Systemic Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasm Metastasis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2018-10-05
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a study in adults with various types of advanced cancer. The purpose of the study is to test a medicine called BI 754091 in combination with several other cancer medicines. BI 754091 is an immunotherapy. This means it may help the immune system fight cancer. Such therapies are also called immune checkpoint inhibitors.

How long the participants are in the study depends on whether they benefit from treatment and whether they experience unacceptable side effects. The participants are put into different groups.

Each group receives BI 754091 in combination with another medicine.

The doctors check whether the tumors shrink or disappear. The doctors also check the general health of the participants.


Eligibility criteria: Inclusion Criteria

Master Protocol:

* Provision of signed and dated, written Master informed consent form (ICF) prior to any trial-specific procedures, sampling, or analyses.
* Patient ≥18 years of age at the time of signature of the ICF.
* Eastern Cooperative Oncology Group (ECOG) score: 0 or 1.
* Patient must agree to a pre-treatment biopsy (if archival tissue is not available) and on-treatment tumour biopsy.
* Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement.
* Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be willing and able to use highly effective methods of birth control (that result in a low failure rate of less than 1% per year when used consistently and correctly) during trial participation and for at least 6 months after the last administration of trial medication.

Module A:

- Histologically confirmed diagnosis of one of the following cohorts:

* Cohort 1 GEC - Locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro oesophageal adenocarcinoma (GEC) (defined as primary tumour localisation below the gastro oesophageal junction (GEJ) with prior anti-PD-1 or anti-PD-L1 based treated tumour.
* Cohort 2 Patients with secondary resistance to anti-PD-1 or anti-PD-L1 based therapy: Any advanced or metastatic solid tumour with previously anti-PD-1 or anti-PD-L1 based treatment who progressed after achieving benefit
* Cohort 3 Patients with primary resistance to anti-PD-1 or anti-PD-L1 based therapy: Select advanced or metastatic solid tumour types with previous anti-PD- 1/PD-L1 based treated tumour without achieving benefit.
* All patients must have measurable lesions according to RECIST v1.1
* Patient must agree to pre- and on-treatment tumour biopsies. If archived tumour tissue is available from the last treatment failure, sections may be supplied instead of a pre-treatment biopsy.

Module C:

* Histologically confirmed diagnosis of one of the following cohorts:

  * Cohort 1: GEC: Locally advanced, unresectable or metastatic gastric adenocarcinoma or GEC.
  * Cohort 2: Patients with secondary resistance to anti-PD-1 or anti-PD-L1 based therapy: Any advanced or metastatic solid tumour (excluding NSCLC and melanoma) with previously anti-PD-1 or anti-PD-L1 based treatment which progressed after achieving benefit.
  * Cohort 3: Patients with primary resistance to anti-PD-1 or anti-PD-L1 based therapy: Select advanced or metastatic solid tumour types with previous anti-PD-1/PD-L1 based treated tumour without achieving benefit.
  * Cohort 4: Locally advanced, unresectable or metastatic second line or greater, microsatellite stable (MSS) colorectal cancer.
  * Cohort 5: Advanced Endometrial cancer: Endometrial carcinoma that is pMMR (Mismatch Repair-Proficient)/MSS and is advanced, recurrent, or persistent and has relapsed or is refractory to curative therapy.
* All patients must have at least one measurable lesion according to RECIST v1.1
* Further inclusion criteria apply

Exclusion Criteria

Master Protocol:

* Any investigational treatment anti-tumour treatment within 4 weeks or within 5 half-life periods (whichever is shorter) prior to the initiation of trial treatment.
* More than one anti-PD-(L)1-based treatment regimen prior to entering study
* Major surgery ('major' according to the Investigator's assessment) performed within 12 weeks prior to first trial treatment or planned within 12 months after screening, e.g., hip replacement.
* Known history of severe hypersensitivity reactions to other mAbs or known hypersensitivity to the trial drugs or their excipients.
* Presence of central nervous system (CNS) metastases, unless treated and asymptomatic and off corticosteroids and/or anticonvulsant therapy for at least 2 weeks prior to start of treatment.
* Immunosuppressive corticosteroid doses (\>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of study treatment.
* Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy. Patients who were permanently discontinued from previous anti-PD-1 or anti-PD-L1 therapy because of a immune-related adverse event (irAE).

Module A:

- Previous treatment with an anti-LAG-3 Agent

Module C:

* Unresolved, Grade \>1 toxicity before the start of treatment with the study drug except for hair loss (alopecia) and hypothyroidism that requires thyroid hormone supplements but is asymptomatic under therapy.
* Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure \> New York Heart Association \[NYHA\] II)
* History of severe haemorrhagic or thromboembolic event in the past 12 months
* Known inherited predisposition to bleeding or to thrombosis, in the opinion of the investigator - Further exclusion criteria apply

Primary outcomes:
measure: The primary endpoint of the trial is objective response (OR), defined as best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the Investigator
timeFrame: Up to 32 months
Secondary outcomes:
measure: Duration of response (DoR), defined as the time from first documented CR or PR (RECIST v1.1) until the earlier of disease progression or death among patients with OR
timeFrame: Up to 32 months
measure: Disease control (DC), defined as best overall response of CR, PR, or stable disease (SD) according to RECIST v1.1 as assessed by the Investigator
timeFrame: Up to 32 months
measure: Progression-free survival (PFS), defined as the time from first treatment until PD or death from any cause, whichever occurs earlier
timeFrame: Up to 32 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists-Fort Myers-52980
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists-Saint Petersburg-52979
state: Florida
city: Tallahassee
country: United States
facility: Florida Cancer Specialists-Sarasota-61670
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists - East
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Oklahoma City
country: United States
facility: Oklahoma University School of Community Medicine
state: Oklahoma
city: Chattanooga
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC-Nashville-52568
state: Tennessee
city: Milwaukee
country: United States
facility: Medical College Of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute (University of Alberta)
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute-London-65253
Study officials:
References: