Study of OP-1250 Adminstered as Monotherapy and Compared to Standard of Care for the Treatment of ER, HER2 Advanced or Metastatic Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Olema Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Phenomena and Processes [G] - Metabolism [G03], Phenomena and Processes [G] - Physiological processes [G07]

Trial duration

8 Apr 2024 → ongoing

Decision date (initial)

2024-04-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Olema Pharmaceuticals, Inc.

External identifiers

EU CT number

2023-505871-63-00

ClinicalTrials.gov

NCT06016738

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Pharmacogenetic, Pharmacokinetic, Dose response

1. To evaluate the safety of OP-1250 at the dose levels of 90 and 120 mg
2. To compare PFS, based on a BIRC assessment, between arms of OP-1250 at the selected dose and SOC treatment

Secondary objectives 2

1. 1. To evaluate the ORR, DoR, DCR, CBR, and PFS based on local investigator assessment of palazestrant at the dose levels of 90 and 120 mg 2. To evaluate the PK of palazestrant at the dose levels of 90 and 120 mg 3. To compare OS between arms of palazestrant at selected dose and SOC treatment 4. To evaluate PFS, based on BIRC assessment, in arms of palazestrant at the selected dose and SOC treatment 5. To evaluate OS in arms of palazestrant at the selected dose and SOC treatment 6. To evaluate PFS, based on local investigator assessment 7. To evaluate ORR, based on BIRC assessment 8. To evaluate DoR, based on BIRC assessment 9. To evaluate the CBR, based on BIRC assessment 10. To evaluate ORR, based on local investigator assessment 11. To evaluate DoR, based on local investigator assessment 12. To evaluate CBR, based on local investigator assessment. 13. To evaluate the safety and tolerability 14. To evaluate the PK of palazestrant 15. To evaluate the change from baseline in health-related PROs
2. 1. To evaluate the ORR, DoR, DCR, CBR, and PFS based on local investigator assessment of palazestrant at the dose levels of 90 and 120 mg 2. To evaluate the PK of palazestrant at the dose levels of 90 and 120 mg 3. To compare OS between arms of palazestrant at selected dose and SOC treatment 4. To evaluate PFS, based on BIRC assessment, in arms of palazestrant at the selected dose and SOC treatment 5. To evaluate OS in arms of palazestrant at the selected dose and SOC treatment 6. To evaluate PFS, based on local investigator assessment 7. To evaluate ORR, based on BIRC assessment 8. To evaluate DoR, based on BIRC assessment 9. To evaluate the CBR, based on BIRC assessment 10. To evaluate ORR, based on local investigator assessment 11. To evaluate DoR, based on local investigator assessment 12. To evaluate CBR, based on local investigator assessment. 13. To evaluate the safety and tolerability 14. To evaluate the PK of palazestrant 15. To evaluate the change from baseline in health-related PROs

Conditions and MedDRA coding

ER+, HER2- metastatic breast cancer following endocrine and CDK 4/6 inhibitor therapy

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Adult female or male participants. • ER+, HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy. • Evaluable disease (measurable disease or bone-only disease). • Previously received a CDK4/6 inhibitor in combination with an endocrine therapy in the advanced setting. One additional line of ET as a monotherapy will be allowed. • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. • Adequate hematologic, hepatic, and renal functions. • Female participants can be pre-, peri- or postmenopausal. • Male and pre- or peri-menopausal female participants must be willing to take a GnRH (LHRH) agonist.

Exclusion criteria 1

1. • Symptomatic visceral disease, imminent organ failure, or any disease burden that makes the participant ineligible for endocrine therapy. • Have received prior chemotherapy (including an antibody-drug conjugate) in the advanced/metastatic setting. • Any contraindications to the selected standard of care endocrine therapy in the local prescribing information. • Symptomatic central nervous system metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require immediate treatment • Clinically significant comorbidities such as significant cardiac or cerebrovascular disease, or gastrointestinal disorders that could aff+F120ect absorption of study treatment, and others

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Safety and tolerability, assessed by AEs, SAEs, dose modifications, clinical laboratory parameters (ie, hematology, chemistry, and coagulation), ECGs, and vital signs measurements 2. BIRC-assessed PFS

Secondary endpoints 3

1. 1. Local investigator-assessed ORR, DoR, DCR, CBR, and PFS 2. Plasma levels of OP-1250 at predefined intervals to establish PK parameters (including: Cmax, Cmin, Tmax, AUC, and OP-1250 trough concentration at steady state) 3. Overall Survival 4. BIRC-assessed PFS 5. Overall survival
2. 6. Local investigator-assessed PFS 7. BIRC-assessed ORR 8. BIRC-assessed DoR 9. BIRC-assessed CBR 10. Local investigator-assessed ORR 11. Local investigator-assessed DoR 12. Local investigator-assessed CBR 13. Safety and tolerability, assessed by AEs, SAEs, dose modifications, clinical laboratory parameters (ie, hematology, chemistry, and coagulation), ECGs, performance status, and vital sign measurements
3. 14. Plasma levels of palazestrant at predefined intervals to establish PK parameters (including: Cmax, Cmin, Tmax, AUC, t1/2, and palazestrant trough concentration at steady state) 15. PRO endpoints, assessed using the EORTC-QLQ-C30 and EQ-5D-5L questionnaires

Investigational products

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

Test 4

Comparator 4

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Olema Pharmaceuticals Inc.

Sponsor organisation

Olema Pharmaceuticals Inc.

Address

512 2nd Street

City

San Francisco

Postcode

94107-4135

Country

United States

Scientific contact point

Organisation

Olema Pharmaceuticals Inc.

Contact name

Mark Shilkrut, Study Director

Public contact point

Organisation

Olema Pharmaceuticals Inc.

Contact name

Kristin Brosofsky, Senior Director Clinical Operations

Third parties 10

Locations

13 EU/EEA countries · 95 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 191 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