This Study in Patients With Different Types of Cancer (Solid Tumours) Aims to Find a Safe Dose of Xentuzumab in Combination With Abemaciclib With or Without Hormonal Therapies. The Study Also Tests How Effective These Medicines Are in Patients With Lung and Breast Cancer

NCT03099174 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 1280.182016-003142-85
• Study Type: interventional
• Target: 133
• Locations: 7 countries
• Sites: 30

Brief Summary

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."

Conditions

Neoplasms; Breast Neoplasms

Outcome Measures

Primary Outcomes (5)

• [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.

  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.

  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.

  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.

  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.

  Up to 18.5 months.

Secondary Outcomes (6)

• [Cohorts E, D1 and D2] Disease Control (DC)

  Up to 35.2 months.

• [Cohorts E, F, D1 and D2] Time to Objective Response

  Up to 21.9 months.

• [Cohorts E, F, D1 and D2] Duration of Objective Response

  Up to 27.2 months.

• [Cohorts E, F, D1 and D2] Duration of Disease Control

  Up to 33.1 months.

• [Cohorts E, F, D1 and D2] Progression-free Survival (PFS)

  Up to 33 months.

Study Arms (8)

Cohort A: Xentuzumab 1000 mg & 150 mg Abemaciclib

EXPERIMENTAL

Patients with solid tumours received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal.

Drug: Xentuzumab; Drug: Abemaciclib

Cohort B: Xentuzumab 1000 mg & 150 mg Abemaciclib & 2.5 mg Letrozole

EXPERIMENTAL

Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 2.5 mg Letrozole (once daily film-coated tablet).

Drug: Xentuzumab; Drug: Abemaciclib; Drug: Letrozole

Cohort C: Xentuzumab 1000 mg & 150 mg Abemaciclib & 1 mg Anastrozole

EXPERIMENTAL

Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 1 mg Anastrozole (once daily film-coated tablet).

Drug: Xentuzumab; Drug: Abemaciclib; Drug: Anastrozole

Cohort D: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant

EXPERIMENTAL

Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).

Drug: Xentuzumab; Drug: Abemaciclib; Drug: Fulvestrant

Cohort E: Xentuzumab 1000 mg & 150 mg Abemaciclib

EXPERIMENTAL

Patients with non-small cell lung cancer (NSCLC) received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal.

Drug: Xentuzumab; Drug: Abemaciclib

Cohort F: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant

EXPERIMENTAL

Patients with HR+ HER2- breast cancer \& non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).

Drug: Xentuzumab; Drug: Fulvestrant; Drug: Abemaciclib

Cohort D1: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant

EXPERIMENTAL

Patients with HR+ HER2- breast cancer \& with visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).

Drug: Xentuzumab; Drug: Fulvestrant; Drug: Abemaciclib

Cohort D2: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant

EXPERIMENTAL

Patients with HR+ HER2- breast cancer \& with non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).

Drug: Xentuzumab; Drug: Fulvestrant; Drug: Abemaciclib

Interventions

Xentuzumab DRUG

Once weekly administrated through one hour intravenous infusion

Cohort A: Xentuzumab 1000 mg & 150 mg Abemaciclib; Cohort B: Xentuzumab 1000 mg & 150 mg Abemaciclib & 2.5 mg Letrozole; Cohort C: Xentuzumab 1000 mg & 150 mg Abemaciclib & 1 mg Anastrozole; Cohort D1: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant; Cohort D2: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant; Cohort D: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant; Cohort E: Xentuzumab 1000 mg & 150 mg Abemaciclib; Cohort F: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant

Abemaciclib DRUG

Treatment/28-day cycle p.o. Q12H on Days 1-28 (dose determined in Cohort A) Abbreviations: PO = orally; Q12H = every 12 (± 2) hours

Cohort A: Xentuzumab 1000 mg & 150 mg Abemaciclib; Cohort B: Xentuzumab 1000 mg & 150 mg Abemaciclib & 2.5 mg Letrozole; Cohort C: Xentuzumab 1000 mg & 150 mg Abemaciclib & 1 mg Anastrozole; Cohort D: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant; Cohort E: Xentuzumab 1000 mg & 150 mg Abemaciclib

Letrozole DRUG

Once a day

Cohort B: Xentuzumab 1000 mg & 150 mg Abemaciclib & 2.5 mg Letrozole

Anastrozole DRUG

Once a day

Cohort C: Xentuzumab 1000 mg & 150 mg Abemaciclib & 1 mg Anastrozole

Fulvestrant DRUG

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

Cohort D1: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant; Cohort D2: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant; Cohort D: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant; Cohort F: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Cohorts
• Age ≥ 18 years (≥20 years for Japan only) at screening
• Signed and dated written informed consent in accordance with GCP (Good Clinical Practice ) and local legislation prior to admission to the trial
• WHO/ECOG (World Health Organization / Eastern Cooperative Oncology Group) performance status 0-1 assessed at screening
• Patient must be able to swallow oral capsules or tablets
• Cohort A (Solid Tumours) \& Cohort E (NSCLC):
• \- Male or female patients ready and able to use highly effective methods of birth control during the study and for 3 weeks following the last dose of abemaciclib per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. Women of childbearing potential must have a negative serum pregnancy test at screening.
• Cohort A (Solid Tumours)
• Patients with histologically or cytologically confirmed diagnosis of advanced and/or metastatic, measurable or evaluable, non-resectable solid tumours
• Patients must have received and failed, or have been intolerant to, all treatment known to confer clinical benefit or have no therapeutic options available as deemed appropriate by their treating physician
• Life expectancy ≥ 3 months in the opinion of the investigator assessed at screening;
• Cohorts B, C, D (dose finding, Breast Cancer) \& Cohort D1 and Cohort D2 (Breast Cancer):
• Women who have postmenopausal status due to either surgical/natural menopause or chemical ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin or radiation-induced ovarian suppression.
• \-- postmenopausal status due to surgical/natural menopause requires at least one of the following conditions:
• prior bilateral oophorectomy

You may not qualify if:

• All - Cohorts A, B, C, D (dose finding), E and F \& Cohort D1 and Cohort D2 (Breast Cancer):
• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial
• Previous treatment in this trial
• Currently enrolled in another investigational device or drug study, or less than 21 days since ending another investigational device or drug study(s), or receiving other investigational treatment(s).
• Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable study subject or unlikely to complete the trial
• Prior anti-cancer chemotherapy, biological or radiation therapy, androgens, thalidomide, other anticancer agents, or any investigational drug within 21 days (14 days for non-myelosuppressive agents); and/or 4 weeks for immunotherapy, before starting any of the trial drugs.
• Prior radiotherapy to ≥ 25% of bone marrow regardless of when it was received
• Unresolved treatment related toxicity from previous therapy of \> CTCAE grade 1 at study entry (except for stable sensory neuropathy ≤ CTCAE grade 2 and alopecia)
• Previous treatment with IGF-1R targeting compounds
• The patient has serious and/or uncontrolled pre-existing medical condition(s) that, in the judgement of the Investigator, would preclude participation in this study, including interstitial lung disease, severe dyspnoea at rest or requiring oxygen therapy.
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following: ANC \< 1.5 x 10\^9/L, platelets \< 100 x 10\^9/L, haemoglobin \<90g/L, ALT \> 2.5 x ULN or \> 5 x ULN in the presence of liver metastases, total bilirubin \>1.5 x ULN or \>3 x ULN in patients with Gilbert's syndrome, serum creatinine \> 1.5 x ULN concurrent with creatinine clearance ≤ 50 mL/min.
• Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis
• Refractory nausea and vomiting, chronic GI diseases, inability to swallow the product, or previous significant bowel resection that would preclude adequate absorption of abemaciclib or resulting in baseline Grade 2 or higher diarrhoea
• Patients with Diabetes Type I or uncontrolled Type II (defined by HgBA1C \> 8%).
• Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term including patients with massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and over 50% of liver involvement in metastases.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (30)

University of California Los Angeles

Santa Monica, California, 90404, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06511, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Herlev and Gentofte Hospital

Herlev, 2730, Denmark

Location

Copenhagen University Hospital, Rigshospitalet

København Ø, 2100, Denmark

Location

Docrates Clinic

Helsinki, 00180, Finland

Location

HUCH Comprehensive Cancer Center, building 2

Helsinki, 00290, Finland

Location

Tampere University Hospital

Tampere, 33520, Finland

Location

CRST - Clinical Research Services Turku

Turku, 20520, Finland

Location

HOP Jean Minjoz

Besançon, 25030, France

Location

INS Paoli-Calmettes

Marseille, 13273, France

Location

INS Curie

Paris, 75005, France

Location

Ctr Cario

Plerin Sur Mer, 22190, France

Location

Aichi Cancer Center Hospital

Aichi, Nagoya, 464-8681, Japan

Location

National Cancer Center Hospital East

Chiba, Kashiwa, 277-8577, Japan

Location

Tokai University Hospital

Kanagawa, Isehara, 259-1193, Japan

Location

National Cancer Center Hospital

Tokyo, Chuo-ku, 104-0045, Japan

Location

National Cancer Center

Goyang, 10408, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08907, Spain

Location

Clínica Universidad de Navarra - Madrid

Madrid, 28027, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Quirónsalud Madrid

Pozuelo de Alarcón, 28223, Spain

Location

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms; Breast Neoplasms

Interventions

xentuzumab; abemaciclib; Letrozole; Anastrozole; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2017
• First Posted: April 4, 2017
• Study Start: May 4, 2017
• Primary Completion: May 31, 2023
• Study Completion: May 16, 2024
• Last Updated: June 24, 2025
• Results First Posted: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.

Locations

JP (4); KR (2); ES (8); US (6); FR (4); DK (2); FI (4)