Clinical trial • Phase III • Oncology
Palazestrant / OP-1250 for Estrogen receptor–positive (ER+), HER2-negative advanced/metastatic breast cancer
Phase III trial of Palazestrant / OP-1250 for Estrogen receptor–positive (ER+), HER2-negative advanced/metastatic breast cancer.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Estrogen receptor–positive (ER+), HER2-negative advanced/metastatic breast cancer
- Trial Stage
- Phase III
- Drug Modality
- Small molecule|Peptide/protein/enzyme
Key dates
- Initial CTIS Submission Date
- 20-11-2023
- First CTIS Authorization Date
- 25-03-2024
Trial design
Randomised, open-label, investigator choice standard-of-care endocrine therapy (fulvestrant or aromatase inhibitors: anastrozole, letrozole, exemestane) used per local prescribing information (doses/schedules per local ma; specific trial text does not list comparator dosing in the ctis data).-controlled, adaptive Phase III trial in Belgium, Bulgaria, Netherlands and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Investigator Choice standard-of-care endocrine therapy (Fulvestrant OR Aromatase Inhibitors: Anastrozole, Letrozole, Exemestane) used per local prescribing information (doses/schedules per local MA; specific trial text does not list comparator dosing in the CTIS data).
- Adaptive
- True, dose selection adaptive element: Part 1 randomizes to palazestrant 90 mg, palazestrant 120 mg, and SOC; dose selection assessment when ~40 participants per palazestrant arm have completed 4 cycles (16 weeks); enrollment pauses until selected dose is recommended and Part 2 opens with the selected dose.
- Biomarker Stratified
- True, biomarker: ESR1-activating mutation(s) detected in ctDNA; strata: ESR1-mut vs ESR1-mut-nd
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 510
Stratification factors
- ESR1 activating mutation(s) detected in ctDNA (ESR1-mut vs ESR1-mut-nd)
- Prior lines of endocrine therapy for advanced disease (1 line vs 2 lines)
- Presence of visceral metastases (yes vs no)
Eligibility
Recruits 510 Vulnerable population selected. Informed consent documents are provided (Main ICF and specific Pregnant Participant / Pregnant Partner ICFs). Adult participants provide consent; specific ICFs for pregnant participants/partners are included in the documentation..
- Vulnerable Population
- Vulnerable population selected. Informed consent documents are provided (Main ICF and specific Pregnant Participant / Pregnant Partner ICFs). Adult participants provide consent; specific ICFs for pregnant participants/partners are included in the documentation.
Inclusion criteria
- {"criterion_text":"- Adult female or male participants.\n- ER+, HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy.\n- Evaluable disease (measurable disease or bone-only disease).\n- 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.\n- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n- Adequate hematologic, hepatic, and renal functions.\n- Female participants can be pre-, peri- or postmenopausal.\n- Male and pre- or peri-menopausal female participants must be willing to take a GnRH (LHRH) agonist."}
Exclusion criteria
- {"criterion_text":"- Symptomatic visceral disease, imminent organ failure, or any disease burden that makes the participant ineligible for endocrine therapy.\n- Have received prior chemotherapy (including an antibody-drug conjugate) in the advanced/metastatic setting.\n- Any contraindications to the selected standard of care endocrine therapy in the local prescribing information.\n- Symptomatic central nervous system metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require immediate treatment\n- 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 endpoints
- {"endpoint_text":"- Safety and tolerability, assessed by AEs, SAEs, dose modifications, clinical laboratory parameters (ie, hematology, chemistry, and coagulation), ECGs, and vital signs measurements\n- BIRC-assessed PFS","definition_or_measurement_approach":"Safety and tolerability: assessed by adverse events (AEs), serious adverse events (SAEs), dose modifications, clinical laboratory parameters (hematology, chemistry, coagulation), ECGs, and vital signs. BIRC-assessed PFS: progression-free survival assessed by a blinded independent review committee (BIRC)."}
Secondary endpoints
- {"endpoint_text":"- 1. Local investigator-assessed ORR, DoR, DCR, CBR, and PFS\n- 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)\n- 3. Overall Survival\n- 4. BIRC-assessed PFS\n- 5. Overall survival","definition_or_measurement_approach":"Local investigator assessments of tumor response metrics (ORR, DoR, DCR, CBR, PFS). PK parameters determined from plasma OP-1250 levels (Cmax, Cmin, Tmax, AUC, trough concentration at steady state). Overall survival measured as time from randomization to death. BIRC-assessed PFS as adjudicated by blinded independent review committee."}
- {"endpoint_text":"- 6. Local investigator-assessed PFS\n- 7. BIRC-assessed ORR\n- 8. BIRC-assessed DoR\n- 9. BIRC-assessed CBR\n- 10. Local investigator-assessed ORR\n- 11. Local investigator-assessed DoR\n- 12. Local investigator-assessed CBR\n- 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","definition_or_measurement_approach":"Investigator- and BIRC-assessed tumor response and survival endpoints as above. Safety and tolerability endpoints assessed by AEs, SAEs, dose changes, labs, ECGs, performance status and vital signs."}
- {"endpoint_text":"- 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)\n- 15. PRO endpoints, assessed using the EORTC-QLQ-C30 and EQ-5D-5L questionnaires","definition_or_measurement_approach":"PK endpoints: plasma palazestrant concentrations at predefined intervals to determine Cmax, Cmin, Tmax, AUC, t1/2, and trough concentration at steady state. PROs assessed using EORTC-QLQ-C30 and EQ-5D-5L instruments."}
Recruitment
- Registry Or Advocacy Recruitment
- True, named organisations present in trial documentation/sites: Althaia Xarxa Assistencial Universitaria De Manresa Fundacio Privada (Spain); Centre Jean Perrin (France) (both listed as Patient organisation/association in trial sites/documents).
- Planned Sample Size
- 510
- Recruitment Window Months
- 44
- Consent Approach
- Informed consent obtained from adult participants via a Main ICF. Country- and language-specific ICFs are provided (document titles show ICFs in English, Dutch, French, German, Hungarian, Italian, Portuguese, Spanish, Bulgarian, Czech, Polish, Romanian, Russian/Ukrainian, and others). Specific Pregnant Participant and Pregnant Partner ICFs are included where applicable. No paediatric assent processes are indicated (adults only).
Methods
- GP-letter documents (K2_GP-letter) are included in country-specific materials (indicates use of general practitioner engagement letters to support recruitment).
- Country/site-specific 'Recruitment arrangements' (K1) documents are provided for multiple countries (titles available for BE, BG, NL, ES, HU, IT, DE, FR, PT, RO, etc.), indicating site-level and country-specific recruitment plans (document titles only).
- Patient travel and reimbursement support is provided (role listed: 'Patient Travel and Reimbursement management' by Scout Clinical).
Geography
- Total Number Of Sites
- 104
- Total Number Of Participants
- 382
Belgium
- Earliest CTIS Part Ii Submission Date
- 13-03-2024
- Latest Decision Or Authorization Date
- 10-03-2026
- Processing Time Days
- 727
- Number Of Sites
- 4
- Number Of Participants
- 25
Bulgaria
- Earliest CTIS Part Ii Submission Date
- 01-03-2024
- Latest Decision Or Authorization Date
- 16-03-2026
- Processing Time Days
- 745
- Number Of Sites
- 2
- Number Of Participants
- 9
Netherlands
- Earliest CTIS Part Ii Submission Date
- 27-02-2024
- Latest Decision Or Authorization Date
- 06-03-2026
- Processing Time Days
- 738
- Number Of Sites
- 2
- Number Of Participants
- 10
Spain
- Earliest CTIS Part Ii Submission Date
- 19-03-2024
- Latest Decision Or Authorization Date
- 09-03-2026
- Processing Time Days
- 720
- Number Of Sites
- 20
- Number Of Participants
- 60
Hungary
- Earliest CTIS Part Ii Submission Date
- 11-03-2024
- Latest Decision Or Authorization Date
- 09-03-2026
- Processing Time Days
- 728
- Number Of Sites
- 3
- Number Of Participants
- 18
Austria
- Earliest CTIS Part Ii Submission Date
- 29-02-2024
- Latest Decision Or Authorization Date
- 09-03-2026
- Processing Time Days
- 740
- Number Of Sites
- 2
- Number Of Participants
- 7
Portugal
- Earliest CTIS Part Ii Submission Date
- 04-03-2024
- Latest Decision Or Authorization Date
- 09-03-2026
- Processing Time Days
- 735
- Number Of Sites
- 5
- Number Of Participants
- 25
Italy
- Earliest CTIS Part Ii Submission Date
- 13-03-2024
- Latest Decision Or Authorization Date
- 10-03-2026
- Processing Time Days
- 727
- Number Of Sites
- 17
- Number Of Participants
- 65
Germany
- Earliest CTIS Part Ii Submission Date
- 11-03-2024
- Latest Decision Or Authorization Date
- 12-03-2026
- Processing Time Days
- 731
- Number Of Sites
- 5
- Number Of Participants
- 24
France
- Earliest CTIS Part Ii Submission Date
- 25-01-2024
- Latest Decision Or Authorization Date
- 10-03-2026
- Processing Time Days
- 774
- Number Of Sites
- 13
- Number Of Participants
- 36
Czechia
- Earliest CTIS Part Ii Submission Date
- 19-03-2024
- Latest Decision Or Authorization Date
- 06-03-2026
- Processing Time Days
- 717
- Number Of Sites
- 4
- Number Of Participants
- 37
Poland
- Earliest CTIS Part Ii Submission Date
- 13-03-2024
- Latest Decision Or Authorization Date
- 08-03-2026
- Processing Time Days
- 725
- Number Of Sites
- 13
- Number Of Participants
- 36
Romania
- Earliest CTIS Part Ii Submission Date
- 04-12-2023
- Latest Decision Or Authorization Date
- 16-03-2026
- Processing Time Days
- 832
- Number Of Sites
- 14
- Number Of Participants
- 30
Sponsor
Primary sponsor
- Full Name
- Olema Pharmaceuticals Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- PPD Development LP
- Responsibilities
- Medical Writing and multiple central trial functions (codes listed in CTIS)
- Name
- 4g Clinical LLC
- Name
- Almac Clinical Services Limited
- Responsibilities
- Supply of OP-1250; centrally provided SoC & GnRH/LHRH
- Name
- Medidata Solutions Inc.
- Responsibilities
- ePRO
Third parties
- {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"ESR-1 Mutation Testing","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"ePRO","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Almac Clinical Services Limited","duties_or_roles":"OP-1250; centrally provided SoC & GnRH/LHRH","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Clinical Technology Centre (Ireland) Limited","duties_or_roles":"centrally provided SoC & GnRH/LHRH","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Travel and Reimbursement management","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Medical Writing and other central services (multiple sponsor duties listed)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"PK and tumor tissue sample","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Palazestrant (OP-1250)
- Active Substance
- Palazestrant / OP-1250
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- 1
- Starting Dose
- 90 mg and 120 mg (dose selection evaluated in Part 1)
- Dose Levels
- 90 mg; 120 mg
- Maximum Dose
- 120 mg
- Dose Escalation Increase
- Initial: 90 mg; Following: 120 mg
- Investigational Product Name
- Fulvestrant
- Active Substance
- Fulvestrant
- Modality
- Small molecule
- Routes Of Administration
- INTRAMUSCULAR INJECTION
- Route
- Intramuscular injection
- Authorisation Status
- 2
- Maximum Dose
- 500 mg (maxDailyDoseAmount field)
- Investigational Product Name
- Exemestane
- Active Substance
- Exemestane
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- 2
- Maximum Dose
- 25 mg
- Investigational Product Name
- Goserelin acetate
- Active Substance
- Goserelin acetate
- Modality
- Peptide/protein/enzyme
- Routes Of Administration
- SUBCUTANEOUS INJECTION
- Route
- Subcutaneous injection
- Authorisation Status
- 2
- Maximum Dose
- 3.6 mg
- Investigational Product Name
- Letrozole
- Active Substance
- Letrozole
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- 2
- Maximum Dose
- 2.5 mg
- Investigational Product Name
- Anastrozole
- Active Substance
- Anastrozole
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- 2
- Maximum Dose
- 1 mg
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