A Phase 1b Followed by Phase II Expansion Trial of Combination of Pembrolizumab and ADG106 in Advanced Solid Cancers and Triple Negative Breast Cancer (ComPACT)
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.
• 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.