Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - Other
Status
Ongoing, recruitment ended
Participants planned
35
Countries
2
Sites
7
ER +/HER2- Advanced or Metastatic Breast Cancer
Phase 1b - To assess safety and tolerability of ARV-471 in combination with abemaciclib in participants with ER+/HER2- A/MBC to select a RP2D. Phase 2 - To assess the clinical antitumor activity of ARV-471 in combination with abemaciclib.
Key facts
- Sponsor
- Pfizer Inc.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 27 Dec 2023 → ongoing
- Decision date (initial)
- 2023-08-14
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Pfizer Inc.
External identifiers
- EU CT number
- 2022-502228-34-00
- ClinicalTrials.gov
- NCT05548127
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
Phase 1b - To assess safety and tolerability of ARV-471 in combination with abemaciclib in participants with ER+/HER2- A/MBC to select a RP2D.
Phase 2 - To assess the clinical antitumor activity of ARV-471 in combination with abemaciclib.
Secondary objectives 8
- Phase 1b: To evaluate the overall safety profile.
- Phase 1b: To evaluate antitumor activity of ARV-471 in combination with abemaciclib.
- Phase 1b: To evaluate the plasma exposure of ARV-471, ARV-473, and abemaciclib when ARV-471 and abemaciclib are given in combination.
- Phase 2: To determine additional antitumor activity outcomes of ARV-471 in combination with abemaciclib.
- Phase 2: To further characterize the overall safety profile and tolerability of ARV-471 in combination with abemaciclib.
- Phase 2: To evaluate the plasma exposure of ARV-471, ARV-473, abemaciclib, and abemaciclib active metabolites M2, M18 and M20, when ARV-471 and abemaciclib are given in combination.
- Phase 2: To assess changes from baseline levels in plasma ctDNA with treatment.
- Phase 1b: To evaluate the effect of ARV-471 on PK of abemaciclib and its active metabolites M2, M18, M20.
Conditions and MedDRA coding
ER +/HER2- Advanced or Metastatic Breast Cancer
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10072737 | Advanced breast cancer | 10029104 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening
- Histological or cytological diagnosis of ER+ and HER2- A/MBC that is not amendable to surgical resection with curative intent (≥1% ER+ stained cells on the most recent tumor biopsy)
- Prior anticancer therapies: - At least 1 and no more than 2 lines of prior therapies for advanced/metastatic disease. - One, and only 1 line of any prior CDK4/6 inhibitor-based regimen is required (independent of the setting eg, adjuvant or advanced/metastatic). If prior CDK4/6 inhibitor was permanently discontinued due to an adverse event, the participant will not be eligible.
- Participants must have at least 1 measurable lesion as defined by RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) performance status ( PS) ≤1.
Exclusion criteria 8
- Participants in visceral crisis at risk of life-threatening complications in the short term.
- Participants with a known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions.
- Participants with newly diagnosed brain metastases, or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated, clinically stable and discontinued anti-seizure medications and corticosteroids for at least 14 days prior to enrollment.
- History of any other malignancies within the past 3 years, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated in situ carcinoma of the cervix. All other malignancies must have been curatively treated and with no evidence of disease for >3 years. Participants with inflammatory breast cancer are excluded.
- Impaired cardiovascular function or clinically significant cardiovascular diseases
- Concurrent administration of medications, food, or herb supplements that are strong inhibitors and strong/moderate inducers of CYP3A, and drugs known to predispose to Torsade de Pointes or QT interval prolongation.
- Renal impairment, not adequate liver function and or bone marrow function.
- Known active infection including hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Phase 1b: DLTs during DLT observation period [Cycle 1].
- Phase 2: Confirmed OR (CR or PR) determined by investigator assessment.
Secondary endpoints 5
- Phase 1b ad Phase 2: AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to ARV-471 in combination with abemaciclib. •Laboratory test abnormalities as characterized by type, frequency, intensity (as graded by NCI CTCAE version 5.0), and timing.
- Phase 1b: Confirmed OR (CR or PR) by investigator assessment. • DoR by investigator assessment. • CBR (confirmed CR or PR at any time, or SD ≥24 weeks) by investigator assessment. • PFS by investigator assessment. Phase 2: DoR by investigator assessment. • CBR (confirmed CR or PR at any time, or SD ≥24 weeks) byinvestigator assessment. • PFS by investigator assessment • OS.
- Phase 1b and Phase 2: Plasma concentrations of ARV-471, ARV-473, abemaciclib, and abemaciclib active metabolites M2, M18 and M20.
- Phase 2: ctDNA plasma quantitative changes from pre-treatment to evaluate potential predictability of their associations with clinical outcomes.
- Phase 1b: AUCtau and Cmax of abemaciclib, M2, M18 and M20, with and without coadministration of ARV 471.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD9906032 · Product
- Active substance
- (3S-3-6-4-1-4-1R2S-6-HYDROXY-2-PHENYL-1234-TETRAHYDRONAPHTHALEN-1-YLPHENYLPIPERIDIN-4-YLMETHYLPIPERAZIN-1-YL-3-OXO-1H-ISOINDOL-2-YLPIPERIDINE-26-DIONE
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Authorisation status
- Not Authorised
- MA holder
- PFIZER INC.
- Paediatric formulation
- No
- Orphan designation
- No
Comparator 3
Verzenios 100 mg film-coated tablets
PRD6701106 · Product
- Active substance
- Abemaciclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Authorisation status
- Authorised
- ATC code
- L01EF03 — -
- Marketing authorisation
- EU/1/18/1307/012
- MA holder
- ELI LILLY NEDERLAND B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Verzenios 150 mg film-coated tablets
PRD6701111 · Product
- Active substance
- Abemaciclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Authorisation status
- Authorised
- ATC code
- L01EF03 — -
- Marketing authorisation
- EU/1/18/1307/014
- MA holder
- ELI LILLY NEDERLAND B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Verzenios 50 mg film-coated tablets
PRD6701101 · Product
- Active substance
- Abemaciclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Authorisation status
- Authorised
- ATC code
- L01EF03 — -
- Marketing authorisation
- EU/1/18/1307/010
- MA holder
- ELI LILLY NEDERLAND B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Pfizer Inc.
- Sponsor organisation
- Pfizer Inc.
- Address
- 66 Hudson Boulevard East
- City
- New York
- Postcode
- 10001-2189
- Country
- United States
Scientific contact point
- Organisation
- Pfizer Inc.
- Contact name
- Clinical Medical Lead
Public contact point
- Organisation
- Pfizer Inc.
- Contact name
- Clinical Medical Lead
Third parties 4
| Organisation | City, country | Duties |
|---|---|---|
| Greenphire LLC ORG-100041621
|
King Of Prussia, United States | Other |
| PPD Global Limited ORG-100007533
|
Cambridge, United Kingdom | On site monitoring |
| Icon Clinical Research Limited ORG-100008322
|
Dublin 18, Ireland | Other |
| Pharmaceutical Product Development LLC ORG-100016999
|
Highland Heights, United States | Other |
Locations
2 EU/EEA countries · 7 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruitment ended | 9 | 2 |
| Spain | Ongoing, recruitment ended | 9 | 5 |
| Rest of world
United States, Canada
|
— | 17 | — |
Investigational sites
Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS
Fondazione del Piemonte per l'Oncologia, Strada Provinciale 142 Orba Km 3,95, 10060, Candiolo
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Scienze della salute della donna, del bambino e di sanità pubblica, Largo Francesco Vito 1, 00168, Rome
Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron
Departamento de Oncologia- VHIO, Passeig De La Vall D'hebron 119-129, 08035, Barcelona
Hospital Universitari Dexeus Grupo Quironsalud
Instituto Oncológico Dr Rosell, Calle De Sabino Arana 5-19, 08028, Barcelona
Hospital Universitario 12 De Octubre
Medical Oncology, Bloque D, Avenida De Cordoba S/n, Madrid
Clinica Universidad De Navarra
NA, Calle Marquesado De Santa Marta 1, 28027, Madrid
Clinica Universidad De Navarra
NA, Avenue Pio XII 36, 31008, Pamplona
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2024-03-25 | 2024-06-14 | 2024-09-10 | ||
| Spain | 2023-12-27 | 2024-02-21 | 2024-09-10 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 65 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1 C4891006_Protocol Amendment_EN_Public | PA4 |
| Protocol (for publication) | D1 Protocol Administrative Changes Letter_2022-502228-34-00_C4891006_EN_Public | 1.0 |
| Protocol (for publication) | D1_1 C4891006_Protocol Administrative Change Letter_EN_Public | 1 |
| Protocol (for publication) | D1.1 C4891006_PACL_14Jul2023_Public_ | 1 |
| Protocol (for publication) | D6 C4891006_EORTC QLQ-C30 Worksheet_EN_Public | 3 |
| Protocol (for publication) | D6 C4891006_EORTC QLQ-C30 Worksheet_ES_Public | 3 |
| Protocol (for publication) | D6 C4891006_EORTC QLQ-C30 Worksheet_IT_Public | 3 |
| Protocol (for publication) | D7 C4891006_EQ-5D-5L Health Questionnaire Worksheet_EN_Public | 1.1 |
| Protocol (for publication) | D7 C4891006_EQ-5D-5L Health Questionnaire Worksheet_ES_Public | 1 |
| Protocol (for publication) | D7 C4891006_EQ-5D-5L Health Questionnaire Worksheet_IT_Public | 1.1 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C1 and 2_EN_Public | 5.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C1 and 2_ES_Public | 5.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C1 and 2_IT_Public | 5.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C1-3_EN_Public | 2.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C1-3_ES_Public | 2.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C1-3_IT_Public | 2.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C3 and Beyond_EN_Public | 5.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C3 and Beyond_ES_Public | 5.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C3 and Beyond_IT_Public | 5.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C4 and Beyond_EN_Public | 2.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C4 and Beyond_ES_Public | 2.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary C4 and Beyond_IT_Public | 2.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary Lead-in_EN_Public | 1.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary Lead-in_ES_Public | 1.0 |
| Protocol (for publication) | D8 C4891006_Dosing Diary Lead-in_IT_Public | 1.0 |
| Recruitment arrangements (for publication) | K10 C4891006_ Recruitment Material_OUS website_ClinicalTrials_IT_IT_Public | 1 |
| Recruitment arrangements (for publication) | K10_Recruitment Material_OUS website_Homepage_Artwork_C4891006_ES_EN_Public | 1 |
| Recruitment arrangements (for publication) | K11 C4891006_Recruitment Material_OUS website_Homepage_Artwork_IT_EN_Public | 1 |
| Recruitment arrangements (for publication) | K11_Recruitment Material_OUS website_ProgramStudyPage_Artwork _C4891006_ES_EN_Public | 1 |
| Recruitment arrangements (for publication) | K1a C4891006_Recruitment-Consent procedure_IT_EN_Public | 3 |
| Recruitment arrangements (for publication) | K1a_C4891006_Recruitment-Consent procedure_ES_Public | 2 |
| Recruitment arrangements (for publication) | K2 C4891006_Recruitment Materials_Brochure_IT_IT_Public | 2 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Brochure_C4891006_ES_ES_Public | 2 |
| Recruitment arrangements (for publication) | K3 C4891006_Recruitment Material_OUS website_ProgramStudyPage_Artwork _IT_EN_Public | 1 |
| Recruitment arrangements (for publication) | K3_Recruitment Material_OUS website_ClinicalTrials_C4891006_ES_ES_Public | 1.0 |
| Recruitment arrangements (for publication) | K4 C4891006_Recruitment Material_OUS website_ProgramStudyPage_Artwork _IT_IT_Public | 1.0 |
| Recruitment arrangements (for publication) | K4_Recruitment Material_OUS website_GeneralFAQs_C4891006_ES_ES_Public | 1.0 |
| Recruitment arrangements (for publication) | K5 C4891006_ Recruitment Material_OUS website_StepsToJoin_IT_IT_Public | 1 |
| Recruitment arrangements (for publication) | K5_Recruitment Material_OUS website_Homepage_C4891006_ES_ES_Public | 1.0 |
| Recruitment arrangements (for publication) | K6 C4891006_ Recruitment Material_OUS website_Privacy_IT_IT_Public | 1 |
| Recruitment arrangements (for publication) | K6_Recruitment Material_OUS website_Landing Page_C4891006_ES_ES_Public | 1 |
| Recruitment arrangements (for publication) | K7 C4891006_ Recruitment Material_OUS website_Landing Page_IT_IT_Public | 1 |
| Recruitment arrangements (for publication) | K7_Recruitment Material_OUS website_Privacy_C4891006_ES_ES_Public | 1.0 |
| Recruitment arrangements (for publication) | K8 C4891006_ Recruitment Material_OUS website_Homepage_IT_IT_Public | 1 |
| Recruitment arrangements (for publication) | K8_Recruitment Material_OUS website_StepsToJoin_C4891006_ES_ES_Public | 1.0 |
| Recruitment arrangements (for publication) | K9 C4891006_ Recruitment Material_OUS website_GeneralFAQs_IT_IT_Public | 1 |
| Recruitment arrangements (for publication) | K9_Recruitment Material_OUS website_ProgramStudyPage_C4891006_ ES_ES_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1a C4891006_Country_Main_ICD_IT_Public | NA |
| Subject information and informed consent form (for publication) | L1a C4891006_Main Model ICD_ES_Public | NA |
| Subject information and informed consent form (for publication) | L2a C4891006_ ICD for Optional RRS_IT_Public | 2.0 |
| Subject information and informed consent form (for publication) | L2a C4891006_Treatment Beyond Progression ICD_ES_Public | NA |
| Subject information and informed consent form (for publication) | L3a C4891006_ICD for Optional EOT Biopsy_IT_Public | 2.0 |
| Subject information and informed consent form (for publication) | L3a C4891006_Optional Biopsy ICD_ES_Public | NA |
| Subject information and informed consent form (for publication) | L4a C4891006_ ICD Treatment Beyond Progressions_IT_Public | 2.0 |
| Subject information and informed consent form (for publication) | L4a C4891006_Pregnant Partner Model ICD_Public | 2.0 |
| Subject information and informed consent form (for publication) | L5a C4891006_Country_PPRIF_Italy_IT_Public | 2.0 |
| Subject information and informed consent form (for publication) | L5a C4891006_Main ICD Addendum 1_ES_ES_Public | NA |
| Subject information and informed consent form (for publication) | L6a C4891006_PRIVACY_SUPPLEMENT_CONSENT_IT_Public | 3.0 |
| Subject information and informed consent form (for publication) | L7a C4891006_General_Practitioner_Letter_Template_IT_Public | 2.0 |
| Subject information and informed consent form (for publication) | L8a C4891006_Study_Information_Card_IT_IT_Public | 1.0 |
| Subject information and informed consent form (for publication) | L9a_Addendum_Country_Main_ICD_C4891006_IT_IT_Public | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2 EU SmPC_Abemaciclib_2022-502228-34-00_C4891006_EN_public | 1 |
| Synopsis of the protocol (for publication) | D2 C4891006_Protocol Amendment Synopsis_EN_Public | PA3 |
| Synopsis of the protocol (for publication) | D3 C4891006_Protocol Amendment Synopsis_ES_Public | PA4 |
| Synopsis of the protocol (for publication) | D3 C4891006_Protocol Amendment Synopsis_IT_Public | PA4 |
Application history
7 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-04-21 | Spain | Acceptable 2023-08-14
|
2023-08-14 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-10-09 | Spain | Acceptable 2023-12-04
|
2023-12-04 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-02-16 | Spain | Acceptable 2024-04-15
|
2024-04-15 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-09-30 | Spain | Acceptable 2024-04-15
|
2024-09-30 |
| 5 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-12-09 | Spain | Acceptable 2025-03-20
|
2025-03-20 |
| 6 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-05-09 | Spain | Acceptable 2025-07-11
|
2025-07-14 |
| 7 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-10-29 | Spain | Acceptable 2026-01-19
|
2026-01-21 |