A phase Ia/Ib, open label, multicentre, dose escalation study of BI 905711 in combination with chemotherapy followed by expansion cohorts in patients with advanced gastrointestinal cancers
A study to find the best dose of BI 905711 in combination with chemotherapy and to test whether this dose helps people with advanced gastrointestinal cancers.
Imazu Susumu
Boehringer Ingelheim
2-1-1, Osaki, Shinagawa-ku, Tokyo
+81-120-189-779
ctinfo@boehringer-ingelheim.com
Watabe Aiko
Boehringer Ingelheim
2-1-1, Osaki, Shinagawa-ku, Tokyo
+81-120-189-779
ctinfo@boehringer-ingelheim.com
Not Recruiting
Nov. 24, 2021
100
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
Applicable to both Phase Ia and Phase Ib Cohorts:
1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
2. Of legal adult age (according to local legislation) at screening.
3. Histologically or cytologically confirmed, advanced unresectable or metastatic colorectal adenocarcinoma
4. CRC : Patients who have PD after prior oxaliplatin-based first line therapy or within 6 months after the end of oxaliplatin-based adjuvant therapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status <= 1
6. Life expectancy >= 3 months in the opinion of the investigator
7. Availability and willingness to provide tumor tissue (fresh biopsy or archival) for biomarker analysis.
8.Adequate hepatic, pancreatic, renal and bone marrow functions as defined below:
-Total bilirubin <= 1.5 x institutional upper level of normal (ULN)
-Alanine transaminase (ALT) and Aspartate transaminase (AST) <= 2.5 x institutional ULN or <= 5 x institutional ULN for patients with known liver metastases
-Serum creatinine <=1.5x institutional ULN. If creatinine is > 1.5 x ULN, patient is eligible if concurrent creatinine clearance more than 50 ml/min (more than 0.05L/min) (measured or calculated by CKD-EPI formula or Japanese version of CKD-EPI formula for Japanese patients)
-Absolute neutrophil count (ANC) >= 1.5 x 109/L, >= 1.5 x 103/microL, or more than 1500/mm3
-Platelets >= 100 x 109/ L, >= 100 x 103/microL, or >= 100 x 103/mm3
-Hemoglobin (Hb) >= 8.5 g/dl, >= 85 g/L, or >= 5.3 mmol/L (without transfusion within previous week)
-Serum lipase <= 1.5 institutional ULN
9. Recovery, from any adverse events (AEs) of previous anti-cancer therapies, to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade 1 except for CTCAE grade 2 alopecia or peripheral sensory neuropathy, or other CtCAE grade 2 AEs considered not clinically significant in the inverstigator's opinion.
10. Male or female patients. Women of childbearing potential (WOCBP)1 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.
Additionally, criterion 11 is applicable to Phase Ia cohort only
11. Patient with either measurable or non-measurable disease.
Additionally, criterion 12-14 is applicable to Phase Ib cohorts only
12. At least one target lesion that can be accurately measured per RECIST 1.1
PDAC Patients must also meet the followings:
13. Histologically or cytologically confirmed, advanced unresectable or metastatic CDH17 positive pancreatic adenocarcinoma
14. Patients who have PD after prior platin and/or gemcitabine-based first line therapy.
Applicable to both Phase Ia and Phase Ib cohorts
1. Any prior irinotecan-based therapy in the metastatic setting.
2. Previous systemic anti-cancer therapy within the specified timeframe from the last dose intake to the first dose of trial treatment as follows:
- Any non-investigational drug, including anti-angiogenic agents (bevacizumab or ramucirumab or aflibercept) and anti-EGFR antibodies (cetuximab or panitumumab), within 14 days.
- Any investigational drug or other antibodies including immune checkpoint inhibitors, within 28 days.
3. Currently enrolled in another investigational device or drug trial. Patients who are in follow-up/observation for another clinical trial are eligible.
4. Radiation therapy within 4 weeks prior to start of treatment. However, palliative radiotherapy for symptomatic metastasis is allowed if completed within 2 weeks prior to start of treatment.
5. Any serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the Investigator, would make the patient inappropriate for entry into the trial.
6. Known pathological condition of GI tract, liver and pancreas, excluding the disease under study, that may interfere with assessment of drug safety or may increase the risk of toxicity:
a. inflammatory bowel disease
b. chronic pancreatitis
c. other serious GI pathological conditions by judgment of the investigator e.g. autoimmune disease with GI involvement, unexplained active diarrhea CTCAE v5.0 grade >=2.
7. Known history of human immunodeficiency virus (HIV) infection.
8. Any of the following laboratory evidence of hepatitis virus infection. Test results obtained in routine diagnostics are acceptable if done within 14 days before the informed consent date:
- Positive results of hepatitis B surface (HBs) antigen
- Presence of HBc antibody together with HBV-DNA
- Presence of hepatitis C RNA
9. Previous or concomitant malignancies, other than the one treated in this trial within the last 2 years with the exception of the following:
- Effectively treated non-melanoma skin cancers
- Effectively treated carcinoma in situ of the cervix
- Effectively treated ductal carcinoma in situ
- Other effectively treated malignancy that is considered cured by local treatment
10. Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes the patient an unreliable trial participant or unlikely to comply with the protocol requirements or not epected to complete the trial as scheduled.
11. Women who are pregnant, nursing, or who plan to become pregnant while in the trial; female patients who do not agree to the interruption of breast feeding from the start of study treatment through 6 months after the last study treatment.
12. Presence of uncontrolled or symptomatic brain or subdural metastases. Inclusion of patients with brain metastases who have completed local therapy and are considered stable by the investigator, or with newly identified asymptomatic brain metastases at screening will be allowed. Use of corticosteroids is allowed if the dose was stable for at least 1 week before the baseline MRI.
13. Patients who are under judicial protection and patients who are legally institutionalized
14. Major surgery (major according to the investigator's assessment) performed within 28 days prior to treatment start or planned within 3 months after screening, e.g. hip replacement.
15. Any of the following cardiac criteria:
a. resting corrected QT interval (QTc) >470 msec based on local assessment
b. Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting Electrocardiograms (ECGs), e.g., complete left bundle branch block, third degree heart block.
c. Patients with an ejection fraction (EF) <50% or the lower limit of normal of the institutional standard will be excluded. Only in cases where the Investigator (or the treating physician or both) suspects cardiac disease with negative effect on the EF, will the EF be measured during screening using an appropriate method according to local standards to confirm eligibility (e.g., echocardiogram, multi-gated acquisition scan). A historic measurement of EF no older than 6 months prior to first administration of study drug can be accepted provided that there is clinical evidence that the EF value has not worsened since this measurement in the opinion of the Investigator or of the treating physician or both.
d. Patients with a history of stroke or myocardial infarction within 6 months prior to screening are not permitted.
16. Known hypersensitivity to the trial medications or their excipients
17. The patient has any known history or clinical evidence of Gilbert's Syndrome, or is known to have any of the following genotypes: UGT1A1*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28
18. Any contradictions to the proposed background therapy according to the current approved local label.
20age old over
No limit
Both
Colorectal adenocarcinoma (CRC) and Pancreatic Ductal Adenocarcinoma (PDAC)
Phase Ia: BI 905711 + FOLFIRI + Bevacizumab
Phase Ib: (CRC: Arm A) BI 905711+FOLFIRI+Bevacizumab, (CRC: Arm B) FOLFIRI+Bevacizumab, (PDAC) BI 905711+ FOLFIRI
Phase Ia
- Maximum tolerated dose (MTD) defined as the highest dose with less than 25% risk of the true DLT rate being equal or above 33% during the MTD evaluation period.
- Number of patients with DLTs in the MTD evaluation period.
Phase Ib
- Confirmed objective response (OR) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in patients with measurable disease, defined as the best overall response of complete response (CR) or partial response (PR), from the first administration of trial medication until the earliest of progressive disease (PD), death or last evaluable tumor assessment before start of subsequent anti-cancer therapy.
- In PDAC cohort safety run-in part: number of patients with DLTs during the MTD evaluation period.
Phase Ia
- The following PK parameters will be calculated after study treatment administration, as measured during the first cycle and after multiple cycles:
Cmax: Maximum measured plasma concentration of
BI 905711.
AUC0-t2: Area under the concentration-time curve in plasma of BI 905711
Phase Ib
- Progression-Free Survival (PFS) defined from date of start of treatment to the date of disease progression or death, whichever is earlier as assessed by the investigator according to RECIST 1.1.
- Radiological (CT Scan) tumor shrinkage, defined as the difference between the minimum post-baseline sum of longest diameters of target lesions and the baseline sum of longest diameters of the same set of target lesions according to RECIST 1.1.
- The duration of OR is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or PD is objectively documented (taking as reference for PD the smallest measurements recorded on study) according to RECIST 1.1.
- Disease control, defined as CR, PR, or stable disease (SD) lasting at least 16 weeks according to RECIST 1.1 from the start of treatment until the earliest of PD, death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy.
- The following PK parameters will be calculated after study treatment administration, as measured during the first cycle and after multiple cycles:
Cmax: Maximum measured plasma concentration of
BI 905711 in plasma.
AUC0-t2: Area under the concentration-time curve for
BI 905711 in plasma.
