A Modular Phase I/IIa, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD5335 Monotherapy and in Combination With Anti-cancer Agents in Participants With Solid Tumors
Summary
This research is designed to determine if experimental treatment with Antibody-drug conjugate, AZD5335, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced tumors
Detailed description
This study is a Phase I/IIa modular, open-label, multi-center study of AZD5335 administered either as monotherapy or in combination with other anti-cancer agents in participants with advanced solid malignancies
Arms & interventions
- DrugTorvutatug samrotecan
IV Antibody-drug conjugate
- DrugSaruparib
Oral PARP inhibitor
- DrugBevacizumab
IV Monoclonal antibody
- DrugCarboplatin
IV Alkylating agent
- DrugPalacaparib
Oral PARP inhibitor
- DrugPembrolizumab
IV Biologic
Outcome measures
Primary
Number of participants with adverse events/serious adverse events
Number of participants with incidence of adverse events and with serious adverse events including changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination.
Time frame: From time of Informed Consent to 30 days post last dose.
The number of participants with dose limiting toxicity(DLT), as defined in the protocol
A DLT is defined as any ≥ Grade 3 treatment-emergent AE that occurs during the DLT evaluation period, not attributable to the underlying disease or extraneous causes (as defined in the protocol)
Time frame: From the first dose of torvu-sam on Cycle 1 Day 1 up to and including the planned end of Cycle 1 (At the end of 21 days)
Secondary
Objective Response Rate (ORR)
Time frame: From time of Informed Consent to progressive disease or withdrawal of consent.(approx 2 years)
Duration of Response (DoR)
Time frame: From the first documented response to confirmed progression or death in the absence of disease progression.(approx 2 years)
Disease Control Rate (DCR)
Time frame: From time of Informed Consent until progression.(approx 15 weeks)
Progression free Survival (PFS)
Time frame: From time of first dose of torvu-sam or anti-cancer study agent until the date of objective disease progression or death (by any cause in the absence of progression) (approx 2 years)
Overall Survival (OS)
Time frame: From time of first dose of torvu-sam or anti-cancer study agent until death due to any cause (approx 2 years)
Module 1: Pharmacokinetics of torvu-sam
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam (approx 12 weeks) through 30-day follow-up
Module 1: Pharmacokinetics of torvu-sam: Area Under the concentration-time curve(AUC)
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam (approximately 12 weeks) through 30-day follow-up
Module 1: Pharmacokinetics of torvu-sam: Maximum plasma concentration of the study drug (Cmax)
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam (approximately 12 weeks) through 30-day follow-up
Module 1: Pharmacokinetics of torvu-sam: Time to maximum plasma concentration of the study drug (T-max)
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam (approximately 12 weeks) through 30-day follow-up
Module 1: Pharmacokinetics of torvu-sam: Clearance
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam (approximately 12 weeks) through 30-day follow-up
Module 1: Pharmacokinetics of torvu-sam: Terminal elimination half-life (t 1/2)
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam (approximately 12 weeks) through 30-day follow-up
Module 1: To investigate baseline and on treatment changes in target expression.
Time frame: Baseline and predicted intervals throughout the administration of torvu-sam (approx 2 years)
Module 2: Pharmacokinetics of torvu-sam and saruparib when given in combination.
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam and saruparib (approx 12 weeks) through 30-day follow-up
Module 3: Pharmacokinetics of torvu-sam and bevaczizumab when given in combination.
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam and bevacizumab (approx 12 weeks) through 30-day follow-up
Module 4: Pharmacokinetics of torvu-sam and carboplatin (+/- bevacizumab) when given in combination.
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam and carboplatin (+/- bevacizumab) (approx 12 weeks) through 30-day follow-up
Module 5: Pharmacokinetics of torvu-sam and palacaparib (+/- bevacizumab) when given in combination.
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam and palacaparib (+/- bevacizumab) (approx 12 weeks) through 30-day follow-up
Module 6: Pharmacokinetics of torvu-sam and pembrolizumab (+/- palacaparib) when given in combination.
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam and pembrolizumab (+/- palacaparib).(approx 12 weeks) through 90-day follow-up
Module 2, 3, 4, 5, and 6: Area Under the concentration-time curve (AUC)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 2, 3, 4, 5, and 6: Maximum plasma concentration of the study drug (Cmax)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 2, 3, 4, 5, and 6: Time to maximum plasma concentration of the study drug (T-max)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 2, 3, 4, 5, and 6: Clearance
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 2, 3, 4, 5, and 6: Terminal elimination half-life (t 1/2)
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam (approximately 12 weeks)
Immunogenicity of torvu-sam
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of torvu-sam (approx 2 years) through 30-day follow-up
Eligibility criteria
Study locations (13)
Research Site
Duarte, California, 91010
Research Site
Irvine, California, 92618
Research Site
La Jolla, California, 92093
Research Site
Aurora, Colorado, 80045
Research Site
Louisville, Kentucky, 40202
Research Site
Boston, Massachusetts, 02114
Research Site
Detroit, Michigan, 48201
Research Site
Columbus, Ohio, 43201
Research Site
Portland, Oregon, 97239
Research Site
Providence, Rhode Island, 02903
Research Site
Providence, Rhode Island, 02905
Research Site
Houston, Texas, 77030
Research Site
Fairfax, Virginia, 22031