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)

National University Hospital, Singapore1 site in 1 country51 target enrollmentJune 12, 2023

ConditionsAdvanced Solid Tumor Triple Negative Breast Cancer

InterventionsPembrolizumab & ADG106 (Phase Ib)Pembrolizumab & ADG106 (Phase II)

DrugsPembrolizumab & ADG106 (Phase Ib)Pembrolizumab & ADG106 (Phase II)

Overview

Phase: Phase 1
Intervention: Pembrolizumab & ADG106 (Phase Ib)
Conditions: Advanced Solid Tumor
Sponsor: National University Hospital, Singapore
Enrollment: 51
Locations: 1
Primary Endpoint: Number of participant with treatment related toxicities (Phase Ib)
Status: Recruiting
Last Updated: 9 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

June 12, 2023

End Date

December 31, 2026

Last Updated

9 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

National University Hospital, Singapore

Responsible Party

Sponsor

Eligibility Criteria

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
•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.
•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.

Exclusion Criteria

•Patients will be excluded from the study for any of the following reasons:
•Treatment within the last 30 days with any investigational drug. Participants must have recovered from all adverse events due to previous therapies to ≤grade 1 or baseline. Participants with ≤grade 2 neuropathy may be eligible. Participants with endocrine related AEs of ≤grade 2 requiring treatment or hormone replacement may be eligible.
•Prior treatment with immune checkpoint inhibitor in phase II; prior immune checkpoint inhibitors are allowed for phase Ib
•Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy
•Major surgery within 28 days of study drug administration
•Prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids for radiotherapy-related adverse events, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation lasting ≤2 weeks to a non-CNS site.
•Active infection that requires systemic therapy, and that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
•Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
•Has severe hypersensitivity (≥grade 3) to pembrolizumab and/or any of its excipients.
•Active, known or suspected autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency etc.) is not considered a form of systemic treatment and is allowed.