TACTIVE-U: An Umbrella Study to Investigate the Safety and Antitumor Activity of ARV-471 in Combination With Other Medicines in Adults With ER+ Advanced or Metastatic Breast Cancer, Sub-study B (ARV-471 and Ribociclib)

Overview

Sponsor-declared trial summary

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

2 Jan 2024 → 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

2022-502231-19-00

ClinicalTrials.gov

NCT05573555

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Phase 1b: To assess safety and tolerability of ARV-471 in combination with ribociclib in participants with ER+/HER2- A/MBC to select a RP2D.
DDI Assessment Cohort(s): To evaluate the effect of ARV-471 on PK of ribociclib.
Phase 2: To assess the clinical antitumor activity of ARV-471 in combination with ribociclib.

Secondary objectives 9

1. Phase 1b: To evaluate the overall safety profile.
2. Phase 1b: To evaluate antitumor activity of ARV-471 in combination with ribociclib.
3. Phase 1b: To evaluate the effect of ribociclib on PK of ARV471.
4. Phase 1b: To evaluate the plasma exposure of ARV-471, ARV-473, and ribociclib when ARV-471 and ribociclib are given in combination.
5. Phase 2: To determine additional antitumor activity outcomes of ARV-471 in combination with ribociclib.
6. Phase 2: To further characterize the overall safety profile and tolerability of ARV-471 in combination with ribociclib.
7. Phase 2: To evaluate the plasma exposure of ARV-471, ARV-473, and ribociclib when ARV-471 and ribociclib are given in combination.
8. Phase 2: To assess changes from baseline levels in plasma ctDNA with treatment.
9. DDI Assessment Cohort(s): To evaluate the overall safety profile.

Conditions and MedDRA coding

ER+/HER2- Advanced or Metastatic Breast Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening.
2. 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)
3. Prior anticancer therapies: - At least one and no more than to 2 lines of prior therapies for advanced/metastatic disease - 1 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. If prior CDK4/6 inhibitor required dose reductions due to an adverse event, refer to Section 6.9.1 for the eligibility evaluation.
4. Participants must have at least 1 measurable lesion as defined by RECIST v1.1
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.

Exclusion criteria 9

1. Participants in visceral crisis at risk of life-threatening complications in the short term.
2. Participants with a known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions.
3. Participants with newly diagnosed brain metastases, or symptomatic 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.
4. 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.
5. Impaired cardiovascular function or clinically significant cardiovascular diseases.
6. Concurrent administration of medications, food, or herb supplements that are strong inhibitors and strong inducers of CYP3A, and drugs known to predispose to Torsade de Pointes or QT interval prolongation.
7. Renal impairment, not adequate liver function and or bone marrow function.
8. Known active infection including HBV, HCV, and HIV or AIDS-related illness.
9. In addition, for participants to be enrolled in the DDI Assessment Cohort(s): moderate CYP3A inhibitors and inducers are also prohibited to avoid potential impact on DDI analysis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase 1b: DLTs during DLT observation period (Cycle 1).
2. Fase 2: Confirmed OR (CR or PR) determined by investigator assessment.
3. DDI Assessment Cohort(s): Steady-state AUCtau and Cmax of ribociclib with and without co-administration of ARV-471.

Secondary endpoints 6

1. Phase 1b and 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 ribociclib. •Laboratory test abnormalities as characterized by type, frequency, intensity (as graded by NCI CTCAE version 5.0), and timing.
2. Fase 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) by investigator assessment. · PFS by investigator assessment. · OS.
3. Phase 1b and Phase 2: Plasma concentrations of ARV-471, ARV-473, and ribociclib.
4. Phase 1b: AUCtau and Cmax of ARV-471 with and without co-administration of ribociclib.
5. Phase 2: ctDNA plasma quantitative changes from pre-treatment to evaluate potential predictability of their associations with clinical outcomes.
6. DDI Assessment Cohort(s): - Incidence of AEs and SAEs. - Incidence of laboratory abnormalities. - Incidence of ECG abnormalities.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

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

Locations

2 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 78 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications