Advanced Solid Tumors
Conditions
Keywords
Recombinant Human Hyaluronidase, Immunooncology monotherapy, T cell Immunoglobulin and Immunoreceptor Tyrosine-based Inhibitory Motif Domain (TIGIT), Programmed Cell Death Protein 1 (PD-1), Bispecific immunotherapy, Checkpoint inhibitor
Brief summary
The purpose of this study is to determine the subcutaneous (SC) dose that gives rilvegostomig exposure comparable to the intravenous (IV) exposure, and to evaluate the pharmacokinetics (PK) and safety of SC rilvegostomig in adult participants with advanced solid tumors previously treated with standard of care therapy for whom immunooncology (IO) monotherapy would be deemed appropriate by the investigator.
Detailed description
This is a Phase I, open-label, multicenter, multi-part, dose finding and dose confirmation study to evaluate the PK and safety of SC rilvegostomig. The study includes 2 parts: Part 1 (Dose Finding) and Part 2 (Dose Confirmation). Part 1 will determine a SC rilvegostomig dose co-administered with rHu that yields drug exposure comparable with IV rilvegostomig. It will include 2 planned dose levels (DL1 in Cohort A and DL2 in Cohort B). Additional dose levels will be added, if needed. Part 2 will be initiated once a dose has been identified based on Part 1. This part will evaluate the bioavailability, safety, and tolerability of SC rilvegostomig + rHu.
Interventions
DRUGIV Rilvegostomig
Rilvegostomig administered IV.
DRUGRecombinant Human Hyaluronidase (rHu)
rHu administered subcutaneously.
DRUGSC Rilvegostomig
Rilvegostomig administered subcutaneously.
DRUGSC rilvegostomig + rHu
SC rilvegostomig + rHu administered subcutaneously.
Sponsors
AstraZeneca
Parexel
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented advanced (metastatic and/or unresectable) solid tumor. * Participants must have received prior anticancer treatment for the disease under study. * IO monotherapy deemed appropriate by the investigator. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment with no deterioration. * Minimum life expectancy of ≥ 12 weeks at enrollment. * Adequate organ and marrow function. * Body weight ≥ 30 kg.
Exclusion criteria
* Any severe or uncontrolled systemic diseases, which makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol. * History of organ transplant. * History of another primary malignancy that was active within past 2 years. * Persistent toxicities caused by previous anticancer treatment(s) excluding alopecia, not yet improved to Grade ≤ 1 or baseline. * Unstable, symptomatic brain metastasis or spinal cord compression. * History of leptomeningeal carcinomatosis. * Active primary immunodeficiency/active infectious disease including tuberculosis (TB), human immunodeficiency virus (HIV) infection or hepatitis A, B or C infection. * History of clinically significant arrhythmia, cardiomyopathy of any etiology; symptomatic congestive heart failure, history of myocardial infarction within the past 6 months. * Uncontrolled intercurrent illness including but not limited to ongoing or active known infection; interstitial lung disease (ILD), serious chronic gastrointestinal conditions associated with diarrhea; active non-infectious skin disease requiring systemic treatment. * Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment. * Known allergy or hypersensitivity to rilvegostomig, hyaluronidase, or any excipients of the investigational products. * Participants experienced a toxicity to prior immunotherapy that led to permanent discontinuation of prior immunotherapy. * Prior anticancer treatment, including immunotherapy, up to 28 days prior to the first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the Concentration-time Curve During One Dosing Interval (AUCtau) | From Day 1 up to end of Cycle 2 in Part 1 and end of Cycle 1 in Part 2 (each cycle will be of 3 weeks) | Bioavailability based on AUCtau at first SC dose will be determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) | From Day 1 up to 90 days post last dose (Up to approximately 29 months) | To assess safety and tolerability of SC rilvegostomig. Safety and tolerability will be evaluated in terms of AEs (graded by CTCAE version 5.0), clinical laboratory assessments, vital signs, physical examinations, and ECOG performance status. |
| Observed Lowest Concentration before the Next Dose is Administered (Ctrough) | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of rilvegostomig (approximately 29 months). | To assess drug exposure (Ctrough) of SC rilvegostomig comparable to that of IV rilvegostomig. |
| Average drug concentration over a dosing interval (Cavg) | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of rilvegostomig (approximately 29 months). | To assess drug exposure (Cavg) of SC rilvegostomig comparable to that of IV rilvegostomig. |
| AUCtau | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of rilvegostomig (approximately 29 months). | To assess drug exposure of SC rilvegostomig comparable to that of IV rilvegostomig. |
| Serum rilvegostomig concentration | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of rilvegostomig (approximately 29 months). | To assess drug exposure (serum concentration) of SC rilvegostomig comparable to that of IV rilvegostomig. |
Countries
South Korea, Spain, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed