A Phase I/IIa Study of AZD8205 given alone or in Combination with Anticancer Drugs, in Participants with Advanced or Metastatic Solid Malignancies
- Conditions
- breast cancer, biliary tract, ovarian, and endometrial cancer.MedDRA version: 20.0Level: PTClassification code: 10033128Term: Ovarian cancer Class: 100000004864MedDRA version: 21.0Level: PTClassification code: 10014733Term: Endometrial cancer Class: 100000004864MedDRA version: 20.0Level: PTClassification code: 10006187Term: Breast cancer Class: 100000004864MedDRA version: 20.0Level: PTClassification code: 10004668Term: Biliary neoplasm Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2022-502759-70-01
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 280
Signed informed consent, If clinically feasible, must consent to provide fresh tumor biopsies in screening, Relapsed/metastatic solid tumors with prior adequate SoC therapy for the tumor type and stage, Additional Inclusion Criteria for Part A (Dose Escalation): Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, CCA, or endometrial cancer which is progressing, Additional Inclusion Criteria for Part A (Dose Escalation) PDx backfill cohort criteria: At least 1 tumor suitable for biopsy and consent to having fresh biopsies, Consent to provide adequate baseline tumor sample, = 18 years, ECOG PS 0-1, Measurable disease per RECIST v1.1, Life expectancy = 12 weeks, Adequate organ and marrow function as described in the protocol, Compliance with the protocol, Contraceptive use, Additional Inclusion Criteria for Part B (Dose Expansion): Participants must have histologically or cytologically confirmed metastatic or locally advanced and recurrent disease for the respective cohort, Additional Inclusion Criteria for Part B (Dose Expansion) Cohort B1 (BTC): Histologically/cytologically verified, non-resectable, recurrent, or metastatic biliary tract carcinoma, Additional Inclusion Criteria for Part B (Dose Expansion) Cohort B2 (Ovarian cancer): Histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, Additional Inclusion Criteria for Part B (Dose Expansion) Cohort B2A Platinum-resistant disease: Prior PARP inhibitors or bevacizumab if eligible, Additional Inclusion Criteria for Part B (Dose Expansion) Cohort B2B Platinum-sensitive disease: Platinum-sensitive disease is defined as radiographic progression greater than 6 months from last dose of most recent platinum therapy., Additional Inclusion Criteria for Part B (Dose Expansion) Cohort B2B Platinum-sensitive disease: Prior PARP inhibitors or bevacizumab if eligible, Additional Inclusion Criteria for Part B (Dose Expansion) - Cohort B3 (HER2-negative breast cancer) [IHC: 0, 1+, 2+/ISH-] Cohort B3A (HR+ HER2-negative breast cancer): HER2-negative [ICH: 0, 1+, 2+/ISH-] and HR+, Adequate venous access, Additional Inclusion Criteria for Part B (Dose Expansion) Cohort B3B (TNBC): HER2-negative [IHC: 0, 1+, 2+/ISH-] and HR-, Additional Inclusion Criteria for Part B (Dose Expansion) Cohort B3C (HR±, HER2-negative breast cancer): HER2-negative [IHC: 0, 1+, 2+/ISH-], HR+ or
Spinal cord compression or a history of leptomeningeal carcinomatosis., Previous enrollment and treatment in the present study., Brain metastases unless treated, asymptomatic, stable, and not requiring continuous corticosteroids., Additional Exclusion Criteria for Part B Dose Expansion Cohorts B2A and B2B: Low-grade/borderline ovarian tumors are not eligible., Treatment with any of the following within the protocol defined time periods prior to the first dose of study intervention: nitrosourea or mitomycin C, any investigational agents, cytotoxic treatment, non-cytotoxic drugs, biological products including immuno-oncology agents, radiotherapy, major surgery., Unresolved toxicities of Grade = 2 from prior therapy (excluding vitiligo, alopecia, controlled endocrine disorders, and chemotherapy-induced Grade 2 neuropathy)., Active infection, including tuberculosis and infections with HBV, HCV or HIV. Certain exceptions apply for past or resolved HBV/HCV infections., History of ILD/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out., Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses., History of another primary malignancy, with the exceptions listed in the protocol., Participants with any of the cardiac criteria detailed in the protocol., Uncontrolled intercurrent illness within the last 12 months., Has substance abuse or any other medical conditions., Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention. Exclusions apply for COVID-19 vaccines., Currently pregnant, lactating, breastfeeding, or intend to become pregnant during the study., Concurrent enrollment in another study, unless it is an observational study or during the follow-up period of an interventional study., Participants with a known hypersensitivity to study intervention or any of its excipients., Involvement in the planning and/or conduct of the study., Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety and tolerability and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of AZD8205 as monotherapy and in combination with anticancer agents.;Secondary Objective: To assess the preliminary anti-tumor activity of AZD8205 as monotherapy and in combination with anticancer agents., To characterize the Pharmacokinetics (PK) of AZD8205 in monotherapy and in combination with anticancer agents., To determine the immunogenicity of AZD8205 as monotherapy and in combination with anticancer agents.;Primary end point(s): Incidence of AEs/SAEs, Incidence of DLTs, Changes from baseline in laboratory findings, ECGs and vital signs, Changes in physical examination (including ECOG)
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Radiological response evaluated according to RECIST v1.1 - objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS).;Secondary end point(s):Plasma concentrations of AZD8205, anti-B7-H4 antibody (INT016) and total unconjugated warhead (AZ14170132).;Secondary end point(s):Plasma parameters of AZD8205, INT016 and AZ14170132, including but not limited to area under the concentration-time curve (AUC), maximum observed concentration (Cmax), time to reach maximum concentration (tmax), clearance and half-life, as data allow.;Secondary end point(s):The number and percentage of participants who develop anti-drug antibody (ADAs).