Advanced Solid Tumor
Conditions
Keywords
Advanced solid tumors, PROTAC, HPK1, MAP4K1, Immune checkpoint inhibitor, Non-small cell lung cancer (NSCLC), Renal cell carcinoma (RCC), Melanoma, Gastric cancer, Gastroesophageal cancer, Esophageal cancer, Head and Neck Squamous cell carcinoma (HSNCC), Urothelial carcinoma (UC), Colorectal Cancer (CRC), Triple-negative breast cancer (TNBC), Ovarian cancer, Cervical cancer, Merkel cell carcinoma, Skin squamous cell carcinoma (SCC), Nasopharyngeal carcinoma, Small cell lung cancer (SCLC), Hepatocellular carcinoma (HCC)
Brief summary
This is a study to evaluate the safety and potential anti-tumor activity of an investigational drug called ARV-6723, in participants with advanced solid tumors. This is an open-label study which means that participants and study staff will know that all participants will receive ARV-6723. The investigational drug ARV-6723 will be given as an oral tablet on its own and also in combination with other drugs. Researchers think that ARV-6723 can help the body's immune system to better recognize, attack, and destroy cancer cells in adults with advanced solid tumors. ARV-6723 is an investigational drug, and this is the first time ARV-6723 will be used in humans. Depending on the treatment assignment, the investigational drug, ARV-6723, will be given as an oral tablet either on its own (monotherapy) or in combination with pembrolizumab, either through a vein (intravenously or IV) or through an injection beneath the skin (subcutaneously or SQ). This study will include multiple parts: In Part A1 (Phase 1a), different small groups of participants will receive lower to higher doses of ARV-6723 as monotherapy or in combination with standard-dose of pembrolizumab. In Part A2 (Phase 1b), two groups of participants with specific tumor indication(s) (TBD) will receive one of two doses selected based on information from Part A1. Details of Part B will be determined based on information generated from Part A.
Interventions
DRUGARV-6723
Oral daily dose of ARV-6723 at an assigned dose.
DRUGPembrolizumab
IV infusion or SQ injection Q3W at an assigned dose.
DRUGSOC
Investigator's choice of SOC drugs.
Sponsors
Arvinas Inc.
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
Part A1 dose escalation and A2 dose optimization: Participants must meet all of the following criteria: * Have a histologic or cytologic diagnosis of unresectable or metastatic solid tumor malignancy. * Have previously received at least one prior therapy targeting programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), and/or another T-cell co-stimulatory or immune checkpoint pathway, in any treatment setting (including neoadjuvant or adjuvant). * Have received prior SOC therapy appropriate for their disease type and stage and have no remaining available treatment options with established clinical benefit; or, in the opinion of the investigator, are unlikely to tolerate or derive clinically meaningful benefit from appropriate SOC therapy; or have declined SOC therapy. * Participants must have demonstrated radiographic progression and have at least 1 measurable lesion per RECIST v1.1 that has not been previously irradiated or has demonstrated progression of disease since radiation therapy. * ECOG PS 0 or 1 or equivalent. Participants with ECOG PS 2 may be considered upon discussion with the Sponsor Medical Monitor. * Participants with adequate organ function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A1: Number of Dose-Limiting Toxicities (DLTs) of ARV-6723 | 21 days from first ARV-6723 administration | Number of participants within a dose escalation cohort with adverse events (AEs) meeting protocol defined dose limiting toxicities during cycle 1 (21 days). |
| Part A1: Number of Participants With Adverse Events (AEs) | From the first dose of ARV-6723 through at least 28 days after the last dose (up to approximately 4.7 years) | AEs as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\]), timing, seriousness, and relationship to study intervention as a measure of safety and tolerability. |
| Part A2: Number of Participants With AEs | From the first dose of ARV-6723 through at least 28 days after the last dose (up to approximately 4.7 years) | AEs as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\]), timing, seriousness, and relationship to study intervention as a measure of safety and tolerability. |
| Part A2: Overall Response Rate (ORR) by computed tomography/magnetic resonance imaging (CT/MRI) Using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) Criteria Per Investigator Assessment | Approximately 24 months | ORR is defined as the proportion of participants reaching a confirmed complete response (CR) or partial response (PR) to the study treatment based on investigator assessment using RECIST 1.1 criteria. |
| Part B: ORR by CT/MRI using RECIST v1.1 Criteria Per Investigator Assessment | Approximately 24 months | ORR is defined as the proportion of participants reaching a confirmed complete response (CR) or partial response (PR) to the study treatment based on investigator assessment using RECIST 1.1 criteria. |
Secondary
| Measure | Time frame |
|---|---|
| Part A1: Area Under the Plasma or Blood Concentration-Time Profile During a Dosing Interval (AUCtau) | At predefined intervals throughout the treatment period, up to approximately 9 months after first dose. |
| Part A1: Area Under the Plasma or Blood Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (Clast) (AUClast) | At predefined intervals throughout the treatment period, up to approximately 9 months after first dose. |
| Part A1: Maximum Plasma or Blood Concentration (Cmax) | At predefined intervals throughout the treatment period, up to approximately 9 months after first dose. |
| Part A1: Lowest Plasma Concentration Immediately Prior to Dosing(Ctrough) | At predefined intervals throughout the treatment period, up to approximately 9 months after first dose. |
| Part A1: Apparent Plasma Clearance at Steady State (CL/F) | At predefined intervals throughout the treatment period, up to approximately 9 months after first dose. |
| Part A1: Time to Maximum Observed Plasma Concentration (Tmax) | At predefined intervals throughout the treatment period, up to approximately 9 months after first dose. |
| Part A1: Apparent Volume of Distribution Divided by the Bioavailability of the Drug (Vz/F) | At predefined intervals throughout the treatment period, up to approximately 9 months after first dose. |
| Part A1: Terminal Elimination Half-Life (t½) | At predefined intervals throughout the treatment period, up to approximately 9 months after first dose. |
| Part A1: Effective Terminal Elimination Half-Life (t½) | At predefined intervals throughout the treatment period, up to approximately 9 months after first dose. |
| Part A1: Accumulation Ratio (Rac) | At predefined intervals throughout the treatment period, up to approximately 9 months after first dose. |
| Part A1: Overall Response Rate (ORR) | Approximately 24 months |
| Part A1: Disease Control Rate (DCR) | Approximately 24 months |
| Part A2: ORR by CT/MRI using iRECIST Criteria Per Investigator Assessment | Approximately 24 months |
| Part A2: Disease Control Rate (DCR) by CT/MRI using RECIST 1.1 and iRECIST criteria per investigator assessment | Approximately 24 months |
| Part B: ORR by CT/MRI Using iRECIST Criteria Per Investigator Assessment | Approximately 24 months |
| Part B: Progression-Free Survival (PFS) | Approximately 24 months |
| Part B: Time to Response (TTR) | Approximately 24 months |
| Part B: Duration of Response (DOR) | Approximately 24 months |
| Part B: DCR by CT/MRI using RECIST v1.1 and iRECIST Criteria Per Investigator assessment | Approximately 24 months |
| Part B: Number of Participants With AEs | From the first dose of ARV-6723 through at least 28 days after the last dose (up to approximately 4.7 years) |
Countries
United States
Contacts
CONTACTArvinas Inc.
Outcome results
None listed