This is a study in adult patients with different types of cancer. The purpose of this study is to find a safe dose of: * Xentuzumab in combination with abemaciclib * Xentuzumab in combination with abemaciclib and hormonal therapies The study also tests whether these medicines make tumours shrink in participants with lung and breast cancer. Participants can stay in the study as long as they benefit from and can tolerate treatment. All participants get xentuzumab infusions and abemaciclib tablets. Participants who have breast cancer get different types of hormonal therapies in addition to xentuzumab and abemaciclib. For all participants, the size of the tumour is measured regularly. Doctors also regularly check the general health of the participants."
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
133
Once weekly administrated through one hour intravenous infusion
Treatment/28-day cycle p.o. Q12H on Days 1-28 (dose determined in Cohort A) Abbreviations: PO = orally; Q12H = every 12 (± 2) hours
Once a day
Once a day
Once a month, with an additional dose given two weeks after the first dose. Each dose is given as two slow injections lasting one to two minutes, with one injection being given into the muscle of each buttock
Treatment/28-day cycle p.o. Q12H on Days 1-28 (dose determined in Cohort D) Abbreviations: PO = orally; Q12H = every 12 (± 2) hours
University of California Los Angeles
Santa Monica, California, United States
Yale University School of Medicine
New Haven, Connecticut, United States
University of Miami
Miami, Florida, United States
University of Minnesota
Minneapolis, Minnesota, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Herlev and Gentofte Hospital
Herlev, Denmark
Copenhagen University Hospital, Rigshospitalet
København Ø, Denmark
Docrates Clinic
Helsinki, Finland
HUCH Comprehensive Cancer Center, building 2
Helsinki, Finland
...and 20 more locations
[Cohort A, B, C & D] Maximum Tolerated Dose (MTD) of Xentuzumab
MTD during the MTD evaluation period (the first 28 day cycle). The MTD is defined as the highest dose with \<25% risk of the true Dose limiting toxicity (DLT) rate \>33%. DLT: adverse event or laboratory abnormality which 1) is related, probably related or possibly related to study drug and 2) meets any of the following criteria, unless that toxicity can be attributed to cancer progression or to identified etiology: CTCAE grade (Gr). 3+ hyperglycaemia (\>48 hours), Gr. 4 hyperglycaemia, hematologic toxicity (\>5 days), Gr. 3+ pneumonitis, febrile neutropenia, thrombocytopenia (Gr. 4 any duration, Gr. 3 w/ bleeding), AST/ALT \> 5x ULN or \> (baseline + 4x ULN), Gr. 3+ diarrhoea, nausea, vomiting (\>2 days), skin rash, fatigue/asthenia (\>7 days), Gr. 3-4 hyperlipidaemia (\>2 weeks), Any AE causing 2-week treatment interruption, non-hematologic toxicities Gr. 3+ (except alopecia, infusion-related reaction), Any significant drug related toxicity qualified as DLT.
Time frame: The first treatment cycle, up to 28 days.
[Cohort A, B, C & D] Number of Patients With DLTs in the MTD Evaluation Period
Number of patients with Dose limiting toxicities in the MTD evaluation period. Dose limiting toxicity (DLT): adverse event or laboratory abnormality which 1) is related, probably related or possibly related to study drug and 2) meets any of the following criteria, unless that toxicity can be attributed to cancer progression or to identified etiology: CTCAE grade (Gr). 3+ hyperglycaemia (\>48 hours), Gr. 4 hyperglycaemia, hematologic toxicity (\>5 days), Gr. 3+ pneumonitis, febrile neutropenia, thrombocytopenia (Gr. 4 any duration, Gr. 3 w/ bleeding), AST/ALT \> 5x ULN or \> (baseline + 4x ULN), Gr. 3+ diarrhoea, nausea, vomiting (\>2 days), skin rash, fatigue/asthenia (\>7 days), Gr. 3-4 hyperlipidaemia (\>2 weeks), Any AE causing 2-week treatment interruption, non-hematologic toxicities Gr. 3+ (except alopecia, infusion-related reaction), Any significant drug related toxicity qualified as DLT.
Time frame: The first treatment cycle, up to 28 days.
[Cohort E] Number of Patients With Objective Response (OR)
Objective response (OR) defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 from date of first treatment administration (including run-in for cohort E) until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeter (mm)). For non-target lesions: disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (\<10mm short axis). Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
Time frame: Up to 26.5 months
[Cohorts D1 and D2] Progression Free Survival (PFS) at 18 Months
Progression free survival (PFS) rate at 18 month defined as the rate of absence of disease progression or death at the 18th month of treatment, where progression is determined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions: Unequivocal progression of existing non-target lesions (Note: the appearance of one or more new lesions is also considered progression). Reported is the progression free survival rate at 18 months, based on a Kaplan-Meier.
Time frame: Up to 18 months.
[Cohort F] Disease Control (DC)
Disease control (DC) defined as best overall response of complete response (CR) or partial response (PR) or confirmed stable disease (SD) (lasting for at least 24 weeks) or Non-CR/ Non-PD (lasting for at least 24 weeks) where best overall response is defined according to RECIST version 1.1 from first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest sum diameters while on study.
Time frame: Up to 18.5 months.
[Cohorts E, D1 and D2] Disease Control (DC)
Disease control (DC) defined as best overall response of complete response (CR) or partial response (PR) or confirmed stable disease (SD) (lasting for at least 24 weeks) or Non-CR/ Non-PD (lasting for at least 24 weeks) where best overall response is defined according to RECIST version 1.1 from first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest sum diameters while on study.
Time frame: Up to 35.2 months.
[Cohorts E, F, D1 and D2] Time to Objective Response
Time to objective response defined as the time from first treatment administration until first documented complete response (CR) or partial response (PR).
Time frame: Up to 21.9 months.
[Cohorts E, F, D1 and D2] Duration of Objective Response
Duration of objective response defined as the time from first documented complete response (CR) or partial response (PR) until the earliest of disease progression or death among patients with objective response.
Time frame: Up to 27.2 months.
[Cohorts E, F, D1 and D2] Duration of Disease Control
Duration of disease control defined as the time from first treatment administration until the earliest of disease progression or death, among patients with disease control.
Time frame: Up to 33.1 months.
[Cohorts E, F, D1 and D2] Progression-free Survival (PFS)
Progression-free survival (PFS) defined as the time from first treatment administration until tumour progression according to RECIST 1.1 or death from any cause, whichever occurs earlier. Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions: Unequivocal progression of existing non-target lesions (Note: the appearance of one or more new lesions is also considered progression).
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Time frame: Up to 33 months.
[Cohorts D1, D2 and F] Objective Response (OR)
Objective response (OR) defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 from date of first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeter (mm)). For non-target lesions: disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (\<10mm short axis). Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
Time frame: Up to 35.2 months.