A study to test different doses of BI 765179 alone and in combination with ezabenlimab in patients with advanced cancer (solid tumors)

Phase 1

Recruiting

• Conditions: patients with advanced solid cancers

• Registration Number: JPRN-jRCT2031210652
• Lead Sponsor: Igarashi Haruki

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-03-08
• Last Update Posted: 27 May 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 127

Inclusion Criteria

1.Patients with locally advanced, unresectable or metastatic solid tumors who are either refractory after standard therapy for the disease or for whom standard therapy is not appropriate
2.Tumor with expected high expression of FAP of the following histologies:
oNon-small cell lung carcinoma (NSCLC)
oGastric cancer
oEsophageal adenocarcinoma or squamous cell carcinoma
oUrothelial bladder carcinoma
oOral squamous cell cancer
oCutaneous malignant melanoma
oCutaneous squamous cell carcinoma
oHepatocellular carcinoma
oPancreatic adenocarcinoma
oColorectal cancer
oMalignant pleural mesothelioma
oCervical squamous cell cancer
oOvarian carcinoma
oTriple-negative breast cancer
3.At least 18 years of age at the time of the consent or over the legal age of consent in countries where that is greater than 18 years
4.Signed and dated, written informed consent (IC) in accordance with ICH-GCP and local legislation prior to admission to the trial
5.At least one measurable lesion outside of CNS as defined per modified RECIST 1.1
6.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7.Adequate liver, bone marrow and renal organ function as follows:
Haematological:
Absolute neutrophil count: >=1.0 x 109 /L (>=1.0 x 1000/ul or >=1.0 x 1000/mm3) (without G-CSF support within the last 3 weeks)
Platelets:>=100 x 109 /L (>=100 x 1000/ul or >=100 x 1000/mm3)
Haemoglobin:>=9.0 g/dL or >5.6 mmol/L (red blood cell transfusion allowed to meet eligibility criteria)
Hepatic:
Total bilirubin:=<1.5 upper limit of normal (ULN) (patients with Gilberts syndrome, total bilirubin must be <2xULN)
AST and ALT:=<2.5 x ULN OR =<5x ULN for patients with liver metastases
Renal:
Creatinine =<1.5 X ULN. If creatinine is >1.5 X ULN, patient is eligible if eGFR (estimated glomerular filtration rate) is>= 30 mL/min/ 1.73 m2 (measured or calculated by CKD-EPI formula or Japanese version of CKD-EPI formula for Japanese patients)
Coagulation:
PT and aPTT:=<1.5 x ULN unless on a stable dose of an anticoagulant
8.Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. These methods must be used during the study and for at least 6 months after the last dose of the study medication. A list of contraception methods meeting these criteria is provided in the patient information.
9.Patients with brain metastases are eligible provided they meet all of the following criteria:
- brain metastases have adequately been treated and are considered stable by the Investigator
- radiotherapy or surgery for brain metastases was completed at least 2 weeks prior to the first administration of BI 765179
- patient is off steroids for at least 7 days (physiologic doses of steroids is permitted, if this was stable for the last 4 weeks)
- the patient is off anti-epileptic drugs for at least 7 days
Back-fill cohorts only:
10.Patient has agreed to and signed an informed consent (IC) form to provide mandatory pre-treatment and on-treatment fresh tumor biopsy
11.At least one lesion (separate from the evaluable target lesion outside of the CNS as defined per RECIST v1.1) that is accessible for mandatory paired pre and on-treatment biopsy

Exclusion Criteria

1.Currently enrolled in another investigational device or drug trial
2.Previous or concomitant malignancies other than the one treated in this trial within the last 2 years except:
o effectively treated non-melanoma skin cancers
o effectively treated carcinoma in situ of the cervix
o effectively treated ductal carcinoma in situ
o other effectively treated malignancy that is considered cured by local treatment
3.Previous treatment with agents targeting CD137
4.Known leptomeningeal disease or spinal cord compression due to disease
5.Anticoagulant treatment that cannot be safely interrupted if medically needed (e.g., biopsy) based on the opinion of the Investigator
6.Persistent toxicity from previous treatments that has not resolved to =< CTCAE Grade 1 (except for alopecia, CTCAE Grade 2 neuropathy, asthenia/fatigue or grade 2 endocrinopathies controlled by replacement therapy)
7.Patient has a diagnosis of immunodeficiency
8.Patient with history of immunosuppressive medication within 14 days prior to the first dose of BI 765179. The following are exceptions to this criterion:
oUse of intranasal, inhaled, or topical corticosteroids, local steroid injections (e.g., intra-articular injections)
oSystemic corticosteroids at physiologic doses =<10 mg/day (prednisone or equivalent)
oPhysiological replacement dose of corticosteroids
9.Prior anti-cancer therapy:
oPatients who have been treated with any other anticancer drug within 3 weeks or within 5 half-life periods (whichever is shorter) prior to first administration of BI 765179
oPatients who have been treated with extensive field radiotherapy including whole brain irradiation within 2 weeks prior to first administration of BI 765179
10.Major injuries or surgery within the past 28 days prior to first administration of BI 765179 with incomplete wound healing, or major surgery planned during study participation, e.g. hip replacement
11.Patients with a previous or planned coronary revascularization (such as stent placement or heart bypass)
12.Any type of chronic non-healing wound/injury
13.Patient with active autoimmune disease or a documented history of autoimmune disease, that requires systemic treatment (i.e. corticosteroids or immunosuppressive drugs). Patients with vitiligo, resolved childhood asthma/atopy, alopecia, or any chronic skin condition that do not require systemic therapy, patients with autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and/or controlled Type 1 diabetes mellitus on a stable insulin regimen may be included if in the opinion of the Investigator it is appropriate and safe to do so
14.Known pulmonary fibrosis
15.Known and documented liver cirrhosis
16.Known renal fibrosis
17.Patients requiring treatment for pleural effusion with sclerosing agents
18.Patients with a history of HCV infection who meet one or both of the following criteria:
oCurative antiviral treatment is not complete
oHCV viral load is above the limit of quantification (HCV RNA positive)
Patients on concurrent HCV therapy can participate provided that the HCV RNA is below the limit of quantification
19.Patients with chronic HBV infection with active disease who meet the criteria for anti HBV therapy (according to local / institutional standard) who have not been treated with suppressive antiviral therapy prior to initiation of study treatment
20.Patients with history of human immunodeficiency virus (HIV) infection who meet one or more of the following criteria
oCD4+ cou

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
-The MTD, defined as the highest dose with less than 25% risk of the true DLT rate being equal to or above 33% during the MTD evaluation period. The MTD will be assessed based on the number of patients experiencing DLTs, graded according to CTCAE version 5.0, during the MTD evaluation period. For the definition of DLTs, refer to Section 5.2.6 and for more information on how the MTD will be determined, refer to Section 7.2.3.<br>-Number of patients experiencing DLTs in the MTD evaluation period.

Secondary Outcome Measures

Name	Time	Method
-Number of patients experiencing DLTs during the on-treatment period (per arm)<br>The following PK parameters of BI 765179 will be evaluated after the first and after multiple administrations of --BI 765179 in both treatment arms: <br>- Cmax(,ss) <br>- AUC0-504(,ss)