DB-1303 for Endometrial cancer

Inclusion criteria

• {"criterion_text":"- Are female adults.\n- Have histologically confirmed endometrial cancer that: − is recurrent, − has a HER2 IHC score of 1+, 2+ (Cohort 1), or 3+ (Cohort 2) as determined by central laboratory testing for HER2 expression, and − is not defined as a true sarcoma.\n- Have measurable disease defined by RECIST 1.1.\n- Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.\n- Have recurrent endometrial cancer and meet any of the following: -developed recurrence within less than 12 months from completing platinum-based chemotherapy as adjuvant therapy for Stage I to III disease, or -developed recurrence after platinum-based chemotherapy in the recurrent / metastatic setting.\n- Have a life expectancy of 12 weeks or longer at screening.\n- Have received prior immune-checkpoint inhibitor (ICI) treatment (i.e., anti-PD-1/anti-PD-L1).\n- Up to three lines of prior therapy are allowed."}

Exclusion criteria

• {"criterion_text":"- Are ineligible for all options in the investigator’s choice chemotherapy arm, per local prescribing information and institutional guidelines (applicable to Cohort 1 only).\n- Are pregnant or breastfeeding or are planning pregnancy during the study or within 7 months after the last dose of study treatment.\n- Have a history of allergies, hypersensitivities, or intolerance to trial treatments including any excipients thereof or to other monoclonal antibodies. Participants who have successfully undergone a desensitization process and are able to tolerate the drug are eligible.\n- Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugates (ADCs).\n- Have left ventricular ejection fraction (LVEF) below 55% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days prior to the first dose of trial treatment.\n- Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of trial treatment.\n- Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.\n- Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, or peritoneal shunt within 2 weeks prior to the first dose of trial treatment.\n- Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.\n- Participants with prior use of immunosuppressive medication within 14 days prior to the first dose of trial treatment, except for intranasal and inhaled corticosteroids or systemic corticosteroids at doses of less than 10 mg/day of prednisone or equivalent. Participants receiving corticosteroids may continue if the dose is stable upon giving main informed consent.\n- Have a lung-specific intercurrent clinically significant illness including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement, and/or prior pneumonectomy (complete).\n- Have uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to the first dose of trial treatment.\n- Have unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than alopecia, fatigue, or endocrinopathies that are well controlled) not yet resolved to Grade 1 or below, or baseline."}

Primary endpoints

• {"endpoint_text":"- Cohort 1: By treatment arm, PFS by BICR defined as the time from randomization to the first objective tumor progression (per RECIST 1.1) or death from any cause, whichever occurs first.","definition_or_measurement_approach":"Progression-free survival (PFS) assessed by blinded independent central review (BICR); defined as time from randomization to first objective tumor progression per RECIST 1.1 or death from any cause, whichever occurs first."}
• {"endpoint_text":"- Cohort 2: For BNT323 monotherapy, objective response rate (ORR) assessed by blinded independent central review (BICR), defined as the proportion of participants with a complete response (CR) or partial response (PR) (per RECIST 1.1) as best overall response with confirmation.","definition_or_measurement_approach":"Objective response rate (ORR) per RECIST 1.1 assessed by blinded independent central review (BICR): proportion of participants with confirmed complete response (CR) or partial response (PR) as best overall response."}

Secondary endpoints

• {"endpoint_text":"- Cohort 1, by treatment arm: overall survival (OS) defined as the time from randomization to death from any cause.","definition_or_measurement_approach":"Overall survival (OS): time from randomization to death from any cause."}
• {"endpoint_text":"- Cohort 1, by treatment arm: PFS assessed by the investigator defined as the time from randomization to the first objective tumor progression (per RECIST 1.1) or death from any cause, whichever occurs first.","definition_or_measurement_approach":"Investigator-assessed PFS per RECIST 1.1: time from randomization to first objective tumor progression or death."}
• {"endpoint_text":"- Cohort 1, by treatment arm: Objective response rate (ORR) defined as the proportion of participants with a complete response (CR) or partial response (PR) (per RECIST 1.1) as best overall response with confirmation.","definition_or_measurement_approach":"ORR per RECIST 1.1: proportion with confirmed CR or PR as best overall response."}
• {"endpoint_text":"- Cohort 1, by treatment arm: Duration of response (DoR) defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (progressive disease [PD] per RECIST 1.1) or death from any cause, whichever occurs first.","definition_or_measurement_approach":"DoR per RECIST 1.1: time from first documented objective response (CR/PR) to first documented progression (PD) or death."}
• {"endpoint_text":"- Cohort 1, by treatment arm: Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs by relationship from the time of initiation of the first dose of trial treatment to 35 days after the last trial treatment dose.","definition_or_measurement_approach":"Safety: treatment-emergent adverse events (TEAEs) captured from first dose until 35 days after last dose; grade ≥3, serious and fatal TEAEs summarized by relationship."}
• {"endpoint_text":"- Cohort 1, by treatment arm: Occurrences of TEAEs leading to drug interruption, dose reduction, or discontinuation of trial treatment.","definition_or_measurement_approach":"Safety: counts and descriptions of TEAEs that result in dose interruption, reduction, or treatment discontinuation."}
• {"endpoint_text":"- For Cohort 2, for BNT323 monotherapy: ORR assessed by the investigator, defined as the proportion of participants with a CR or PR (per RECIST 1.1) as best overall response with confirmation.","definition_or_measurement_approach":"Investigator-assessed ORR per RECIST 1.1: proportion with confirmed CR or PR."}
• {"endpoint_text":"- For Cohort 2, for BNT323 monotherapy: DoR defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (PD per RECIST 1.1) or death from any cause, whichever occurs first.","definition_or_measurement_approach":"DoR per RECIST 1.1 for Cohort 2: time from first objective response to progression or death."}
• {"endpoint_text":"- For Cohort 2, for BNT323 monotherapy: PFS defined as the time from the first dose of trial treatment to the first objective tumor progression (per RECIST 1.1) or death from any cause, whichever occurs first.","definition_or_measurement_approach":"PFS per RECIST 1.1 for Cohort 2: time from first dose to progression or death."}
• {"endpoint_text":"- For Cohort 2, for BNT323 monotherapy: OS defined as the time from the first dose of trial treatment to death from any cause.","definition_or_measurement_approach":"OS for Cohort 2: time from first dose to death from any cause."}
• {"endpoint_text":"- For Cohort 2, for BNT323 monotherapy: Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs by relationship from the time of initiation of the first dose of trial treatment to 35 days after the last trial treatment dose.","definition_or_measurement_approach":"Safety TEAEs for Cohort 2 captured from first dose until 35 days after last dose; summary by grade and relationship."}
• {"endpoint_text":"- For Cohort 2, for BNT323 monotherapy: Occurrences of TEAEs leading to drug interruption, dose reduction, or discontinuation of trial treatment.","definition_or_measurement_approach":"TEAEs resulting in interruption, dose reduction or discontinuation for Cohort 2."}

Primary sponsor

Full Name

BioNTech SE

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

IQVIA Limited

Responsibilities

Duties codes: 1, 12, 13, 2, 5, 6, 8 (per submission metadata)

Name

Bioclinica Inc.

Responsibilities

Clinical Imaging Services, Clinical Adjudication Services

Name

Medidata Solutions Inc.

Responsibilities

Duties codes: 6, 7 (per submission metadata)

Name

4G Clinical B.V.

Responsibilities

Duties code: 3 (per submission metadata)

Name

4g Clinical LLC

Responsibilities

Duties code: 3 (per submission metadata)

Name

Q Squared Solutions LLC

Responsibilities

Speciality lab

Name

Labcorp Central Laboratory Services SARL

Responsibilities

Central Laboratory, tumor IHC

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Central Laboratory, tumor IHC","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Participant Travel & Convenience Solutions","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Quipment","duties_or_roles":"Trial Supplies","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Clinical Imaging Services, Clinical Adjudication Services","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Greece","full_name":"IQVIA RDS Hellas Single Member S.A.","duties_or_roles":"Duties codes: 1, 12, 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Speciality lab","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac Safety Services","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"Duties code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Duties codes: 6, 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Singapore","full_name":"Labcorp Development (Asia) Pte Ltd","duties_or_roles":"PK, ADA analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Duties codes: 1, 12, 13, 2, 5, 6, 8","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"Duties code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"Duties code: 3","organisation_type":"Non-Pharmaceutical company"}