Advanced Solid Tumor, Triple Negative Breast Cancer
Conditions
Keywords
Pembrolizumab, ADG106, Breast Cancer, Triple Negative
Brief summary
This is a phase Ib followed by phase II clinical trial evaluating the safety and efficacy of combination of ADG106 with pembrolizumab in patients with metastatic cancers. The Phase Ib dose finding part will include all solid tumor subtypes with treatment refractory disease, while phase II will focus on only patients with TNBC.
Detailed description
2.1 Hypothesis * Combination of ADG106 and pembrolizumab is safe with a reasonable toxicity profile. * Combination of ADG106 and pembrolizumab is effective and can improve outcomes in patients with advanced TNBC. * Predictive biomarkers may help select patients most likely to benefit from combination therapy. 2.2 Primary Objectives Phase Ib * Evaluate the safety and tolerability of combination of ADG106 with pembrolizumab in patients with advanced solid tumors. * Determine recommended phase II dose (RP2D) of ADG106 in combination with pembrolizumab. Phase II • Evaluate the clinical efficacy of ADG106 plus pembrolizumab in terms of ORR in patient with advanced TNBC with CPS ≥1 2.3 Secondary Objectives Phase Ib • Evaluate preliminary anti-tumor effect of combination of ADG106 with pembrolizumab in terms of ORR, disease control rate (DCR), PFS and OS in patients with treatment refractory solid tumors Phase II * Evaluate clinical efficacy of ADG106 plus pembrolizumab in terms of DCR, PFS and OS in patients with advanced TNBC with CPS≥1 * Evaluate clinical efficacy of ADG106 plus pembrolizumab in terms of ORR, DCR, PFS and OS in patients with advanced TNBC with CPS≥10 2.4 Exploratory Objectives * Evaluate predictive biomarkers (e.g., tumor PD-L1 CPS score) for response to ADG106 plus pembrolizumab. * Evaluate changes in tumor microenvironment with combination of ADG106 plus pembrolizumab. * Evaluate changes in tumor genomic expression profile with combination of ADG106 plus pembrolizumab.
Interventions
DRUGPembrolizumab & ADG106 (Phase Ib)
Drug: ADG106 Administered as an intravenous infusion over 60-90 minutes in the initial cycle and over 30 minutes in subsequent cycle if well tolerated. Pembrolizumab Administered as an intravenous infusion over 30 minutes
DRUGPembrolizumab & ADG106 (Phase II)
Drug: ADG106 Administered as an intravenous infusion over 60-90 minutes in the initial cycle and over 30 minutes in subsequent cycle if well tolerated. Pembrolizumab Administered as an intravenous infusion over 30 minutes
Sponsors
Adagene Inc
Merck Sharp & Dohme LLC
National University Hospital, Singapore
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
* Phase Ib: Patients with advanced solid tumors will be enrolled in a 3+3 dose escalation fashion, with projected enrolment of between 6-18 patients to determine RP2D. Once the RP2D is confirmed, the study will proceed to phase II. * Phase II: Up to a total of 33 patients with advanced triple negative breast cancer will be enrolled.
Eligibility
Sex/Gender
ALL
Age
21 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* 21 years and above of age * Estimated life expectancy of at least 12 weeks. * Has recovered from acute toxicities from prior anti-cancer therapies. * Has a tumor lesion that can be safely biopsied and who is willing to undergo tumor biopsy at baseline before starting study treatment * Phase Ib * Patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have radiological evidence of progressive disease on study entry * There is no upper limit on the number of prior treatments provided all inclusion/
Exclusion criteria
are met. * Prior treatment with immunotherapy is allowed. * Phase II * Patients with histologically or cytologically confirmed TNBC, defined by expression of estrogen (ER) and progesterone receptors (PR) of \<1% and HER2 IHC score of 0 or 1+ or HER2 IHC score of 2+ but HER2 FISH negative. * Received at least 1 line but no more than 2 prior lines of systemic therapy in the metastatic setting, including chemotherapy or targeted therapy (e.g., PARP inhibitors). * Tumor CPS≥1 determined by the DAKO 22C3 assay assessed by local or central laboratory. * Measurable disease by RECIST 1.1 criteria as determined by local radiological review. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. * Adequate bone marrow function and organ function within 2 weeks of study treatment. * Adequate hematologic function defined as: * Absolute neutrophil count (ANC) - 1.5 x 109/L * Platelets - 100 x 109/L * Hemoglobin - 9 x 109/L * Adequate hepatic function defined as: * Bilirubin ≤1.5 times the upper limit of normal (ULN) * ALT or AST ≤ 2.5 times ULN (or ≤5 times ULN with presence of liver metastases) * Adequate renal function defined as: \- Calculated creatinine clearance of ≥ 60 mL/min, calculated using the formula of Cockroft and Gault: (140-Age) x Mass (kg)/(72 x creatinine mg/dL); multiply by 0.85 if female. * Adequate coagulation function as defined by: * International normalised ratio (INR) OR prothrombin time (PT)/activated partial thromboplastin time (aPTT) ≤1.5x ULN unless participant is receiving anticoagulant therapy, for which it will be acceptable as long as PT or aPTT is within therapeutic range of intended use of anticoagulants. * Patients with reproductive potential must use an approved contraceptive method as detailed in appendix A of the protocol during the period and for at least 120 days (corresponding to 5 terminal half-lives for pembrolizumab therapy) plus 30 days (corresponding to a menstruation cycle) for female, and for at least 120 days plus 90 days (corresponding to a spermatogenesis cycle) for male patients. In addition, females with childbearing potential must have a negative serum pregnancy test within 72 hours prior to study enrolment. * Have signed informed consent in accordance with local institutional guidelines, and able to comply with scheduled visits, treatment plan and study related procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participant with treatment related toxicities (Phase Ib) | 3 years | Toxicities will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading Version 5 |
| Objective response rate (ORR) in Phase II | 3 years | Complete and partial clinical response will be measured by RECIST 1.1. |
Countries
Singapore
Contacts
Primary ContactSoo Chin Lee
Backup ContactSoo Chin Lee
Outcome results
None listed