A Phase 1 Study of ADA-011 for Subjects With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This study consists of dose escalation evaluation to determine the safety and tolerability of ADA-011 as a monotherapy and in combination with a checkpoint inhibitor. Following dose escalation, one or more dose expansion cohorts in selected indications will be explored to further evaluate the safety, tolerability, and preliminary efficacy of ADA-011.

Official Title
-----------------
A Phase 1, Open-Label, Multicenter Study of ADA-011 as Monotherapy and in Combination With a Checkpoint Inhibitor for Subjects With Advanced Solid Tumors

Conditions
-----------------
Solid Tumor, Adult

Intervention / Treatment
-----------------
* Drug: ADA-011
* Drug: PD(L)-1 inhibitor


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically documented, incurable or metastatic solid tumor that is advanced (nonresectable) or recurrent and progressing since the last antitumor therapy and for which no recognized standard therapy exists Eastern Cooperative Oncology Group (ECOG) performance status ≤2 Measurable disease per RECIST v1.1 or per other criteria best suited for the specific tumor type being evaluated Adequate organ function Exclusion Criteria: Treatment with any local or systemic antineoplastic therapy (including chemotherapy, hormonal therapy, or radiation) within 2 weeks prior to the first dose of ADA-011 Chronic use of corticosteroids in excess of 10 mg daily of prednisone or equivalent within 4 weeks prior to the first dose of ADA-011 Major trauma or major surgery within 4 weeks prior to the first dose of ADA-011 AEs from prior anticancer therapy that have not resolved to Grade ≤1 except for alopecia Known, central nervous system (CNS) disease involvement, or prior history of NCI CTCAE Grade ≥3 drug-related CNS toxicity. Evidence of active uncontrolled viral, bacterial, or systemic fungal infection Active SARS-CoV-2 infection, irrespective of symptoms. History or risk of severe, chronic, untreated, or currently active autoimmune disease Prior solid organ transplant or has had an allogenic hematopoietic stem cell transplant within the past 20 years Pregnant, lactating, or breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Non-randomized dose escalation followed by dose expansion.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADA-011 Monotherapy Dose Escalation<br>ADA-011 monotherapy will be administered intravenously (IV), every 3 weeks (Q3W) at escalating doses starting with Cycle 1, Day 1, until participant withdrawal. Participants enroll with histologically or cytologically confirmed solid tumors. | Drug: ADA-011<br>* ADA-011 will be administered intravenously (IV) Q3W on a 21-day cycle.<br>|
| Experimental: ADA-011 Monotherapy Dose Expansion<br>ADA-011 monotherapy with the preliminary recommended phase 2 dose (RP2D) of ADA-011, in participants with histologically or cytologically confirmed solid tumors. | Drug: ADA-011<br>* ADA-011 will be administered intravenously (IV) Q3W on a 21-day cycle.<br>|
| Experimental: Combination Therapy Dose Escalation<br>Combination therapy with ADA-011 and PD(L)-1 inhibitor (at escalating ADA-011 doses) will be administered IV Q3W, starting with Cycle 1, Day 1 in participants with histologically or cytologically confirmed solid tumors. | Drug: ADA-011<br>* ADA-011 will be administered intravenously (IV) Q3W on a 21-day cycle.<br>Drug: PD(L)-1 inhibitor<br>* PD(L)-1 inhibitor will be administered intravenously (IV) Q3W.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced an Adverse Event (AE) | An AE is any unfavorable and/or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. The number of participants who discontinued study treatment due to an AE will be presented. | 36 months | 
| Number of Dose-Limiting Toxicities (DLTs) | DLTs will be evaluated according to NCI CTCAE v5.0 and are generally defined as grade 3 or higher toxicities which are deemed to be medically significant. | 21 days (cycle 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Profile of Participants Treated with ADA-011 (AUC) | Pharmacokinetic (PK) parameters of ADA-011 including area under the curve (AUC) will be evaluated for all participants in the dose escalation cohorts. | 36 months | 
| Pharmacokinetic (PK) Profile of Participants Treated with ADA-011 (Cmax) | Pharmacokinetic (PK) parameters of ADA-011 including maximum concentration (Cmax) will be evaluated for all participants in the dose escalation cohorts. | 36 months |