A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer

Triple Negative Breast Neoplasms Clinical Trial

— BEGONIA  

Official title:

A Phase IB/II, 2-stage, Open-label, Multicenter Study to Determine the Efficacy and Safety of Durvalumab (MEDI4736) + Paclitaxel and Durvalumab (MEDI4736) in Combination With Novel Oncology Therapies With or Without Paclitaxel for First-line Metastatic Triple Negative Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03742102
• Other study ID #: D933LC00001
• Secondary ID: 2018-000764-29
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 21, 2018
• Est. completion date: November 14, 2024

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to determine the efficacy and safety of durvalumab in combination with novel oncology therapies with or without paclitaxel and durvalumab + paclitaxel for first-line metastatic triple negative breast cancer

Description:

This is a Phase IB/II, 2-stage, open-label, multicenter study to determine the efficacy and safety of durvalumab in combination with novel oncology therapies (i.e. therapies designed for immune modulation) with or without paclitaxel and durvalumab + paclitaxel as first-line treatment in patients with metastatic triple negative breast cancer (TNBC). The study is designed to concurrently evaluate potential novel treatment combinations with clinical promise using a 2-stage approach. The study will use a Simon 2-Stage design to evaluate which cohorts may proceed to expansion.

Part 1 is a Phase IB study of safety and initial efficacy, and Part 2 may expand patient enrollment if adequate efficacy signal is observed in Part 1. The treatment regimens evaluated in Part 2 will depend on the evaluation of safety and efficacy outcomes in Part 1.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: November 14, 2024
• Est. primary completion date: November 14, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 130 Years

Eligibility

Inclusion criteria

1. Female

2. At least 18 years of age at the time of screening

3. Patient must have locally confirmed advanced/unresectable or metastatic TNBC.

4. No prior treatment for metastatic (Stage IV) TNBC

5. Patient must have at least 1 lesion, not previously irradiated, that can be accurately measured

6. WHO/ECOG status at 0 or 1 at enrollment

Patients enrolled to Arm 6 (durvalumab and DS-8201a) Must provide documentation of locally determined advanced/unresectable or metastatic TNBC with HER2 low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested)

Patients enrolled in Arm 8 (durvalumab + Dato-DXd) Must have PD-L1 positive tumor as determined by an IHC based assay

Exclusion criteria

1. History of allogeneic organ transplantation

2. Active or prior documented autoimmune or inflammatory disorders

3. Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C virus (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies)

4. Untreated CNS metastases

5. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

6. Any concurrent chemotherapy, IP, or biologic therapy for cancer treatment

7. Female patients who are pregnant, breastfeeding

8. Cardiac Ejection Fraction less than 50%

Patients enrolled in Arm 2 only:

1. Potent inhibitors or inducers or substrates of CYP3A4 or substrates of CYP2C9 or CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)

2. Diagnosis of diabetes mellitus Type I or diabetes mellitus Type II requiring insulin treatment.

3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval

4. Prior treatment with PI3K inhibitors, AKT inhibitors, or mammalian target of rapamycin (mTOR) inhibitors.

Patients enrolled in Arm 5 only: History of venous thromboembolism in the past 3 months

Patients enrolled in Arm 7 and 8 only: Clinically significant corneal disease in the opinion of the Investigator.

Patients enrolled in Arm 6, 7 and 8 only:

1. History of or active interstitial lung disease/pneumonitis

2. Use of chloroquine or hydroxychloroquine in <14 days prior to Day 1 of DS-8201a (Arm 6) or Dato-DXd (DS-1062a; Arm 7 and 8) treatment

3. Patients enrolled in Arm 6 only: Previously been diagnosed as HER2+ or received HER2-targeted therapy.

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Durvalumab
Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8
• Capivasertib
Capivasertib oral bid 4-week cycles; 3 weeks on (dosing on days 2,3,4 and 5) and 1 week off
• Oleclumab
Oleclumab iv Every 2 weeks (q2w) for first 2 cycles (days 1 and 15 in cycles 1 and 2), then every 4 weeks (q4w) starting at cycle 3 day 1
• Paclitaxel
Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off
• Trastuzumab deruxtecan
Trastuzumab deruxtecan iv 3-week cycles (once weekly) q3w
• Datopotamab deruxtecan
Datopotamab deruxtecan iv 3-week cycles (once weekly) q3w

Locations

Country	Name	City	State
Canada	Research Site	Greenfield Park	Quebec
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Poland	Research Site	Gdansk
Poland	Research Site	Gliwice
Poland	Research Site	Kraków
Poland	Research Site	Lublin
Poland	Research Site	Opole
Poland	Research Site	Poznan
Poland	Research Site	Rzeszów
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Oxford
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Columbia	Maryland
United States	Research Site	Dallas	Texas
United States	Research Site	Eugene	Oregon
United States	Research Site	Fairfax	Virginia
United States	Research Site	Flower Mound	Texas
United States	Research Site	Goodyear	Arizona
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Houston	Texas
United States	Research Site	Las Vegas	Nevada
United States	Research Site	McAllen	Texas
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Paul	Minnesota
United States	Research Site	San Antonio	Texas
United States	Research Site	Tucson	Arizona
United States	Research Site	West Hollywood	California
United States	Research Site	Williamsburg	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of,  Poland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events	Part 1: Assessment of safety and tolerability of each treatment arm; Part 2: Endpoints based on Investigator assessment according to RECIST 1.1: ORR (objective response rate): The percentage of evaluable patients with a confirmed Investigator-assessed visit response of CR (complete response) or PR (partial response).	Part1: From informed consent until the safety follow-up visit 3 months after the last dose of study drug. Part 2: From informed consent until the safety follow-up visit 3 months after the last dose of study drug.
Primary	Laboratory findings	Assessment of safety and tolerability of each treatment arm	Part 1: From informed consent until the safety follow-up visit 3 months after the last dose of study drug. Part 2:From informed consent until the safety follow-up visit 3 months after the last dose of study drug.
Secondary	Objective response rate (ORR)	Assessment of the efficacy of each treatment arm according to RECIST 1.1. ORR: The percentage of evaluable patients with a confirmed Investigator-assessed response of CR (complete response) or PR (partial response) Applicable for Part 1 and Part 2.	Approx. 30 months
Secondary	Progression-free survival (PFS).	Assessment of the efficacy of each treatment arm according to RECIST 1.1. PFS: Time from date of first dose until the date of objective radiological disease progression or death (by any cause in the absence of progression); Applicable for Part 1 and Part 2	On-study tumor assessments occur every 8 weeks (Arms 1-5),every 6 weeks (Arms 6-8) until week 48 and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months
Secondary	Duration of response (DoR)	Assessment of the efficacy of each treatment arm according to RECIST 1.1. DoR: Time from date of first detection of objective response (which is subsequently confirmed) until the date of objective radiological disease progression Applicable for Part 1 and Part 2	On-study tumor assessments occur every 8 weeks (Arms 1-5), every 6 weeks (Arms 6-8) until week 48 and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months
Secondary	Overall survival (OS)	OS: Time from date of first dose until the date of death by any cause; Applicable for Part 1 and Part 2	Approx. 30 months
Secondary	Serum concentration of durvalumab and serum or plasma concentration of novel oncology therapies	Assessment of pharmacokinetics (PK) Applicable for Part 1 (Arms 1-8) and for Part 2 (Arm 7)	From cycle 1 day 1 until cycle 7 day 1 (Arms 1-5), from cycle 1 day 1 until cycle 8 day 1 (Arms 6-8) (each cycle is 28 days) and every 12 weeks thereafter until study completion approx. 30 months
Secondary	Presence of anti-drug antibodies (ADAs) for durvalumab and applicable novel oncology therapies	Investigation of the immunogenicity of durvalumab and novel oncology therapies in all applicable treatment arms Applicable for Part 1 (Arms 1-8) and for Part 2 (Arm 7)	From cycle 1 day 1 until cycle 7 day 1 (Arms 1-5), from cycle 1 day 1 until cycle 8 day 1 (Arms 6-8) (each cycle is 28 days) and every 12 weeks thereafter until study completion approx. 30 months
Secondary	Progression-free survival (PFS 6)	PFS at 6 months following date of first dose Applicable for Part 2	On-study tumor assessments occur every 8 weeks until week 48 (Arms 1-5), every 6 weeks until week 48 (Arms 6-8) and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months

External Links

•   https://breastcancerstudylocator.com/