First-in-human Study of OT-A201 in Patients With Selected Hematological Malignancies and Solid Tumors

Study Overview
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Brief Summary
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This phase 1 study is aimed at establishing the safety basis of OT-A201 in the treatment of hematological malignancies and solid tumors. In the dose of escalation part it is to characterize the overall safety and tolerability profile and determine the recommended dose(s) of OT-A201 as monotherapy, and in various combination regimens. Preliminary information about anti-cancer activity will be further explored in the expansion part of the study.

Official Title
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A First-in-human, Dose-escalation Followed by Expansion Study to Assess the Safety and Preliminary Efficacy of a Bispecific Antibody OT-A201 as Monotherapy and in Combination Therapy in Patients With Selected Hematological Malignancies and Solid Tumors

Conditions
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Hematological Malignancy, Solid Tumor

Intervention / Treatment
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* Drug: OT-A201
* Drug: IMids
* Drug: Bevacizumab
* Drug: Paclitaxel
* Drug: TBD Compound


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Histologically or cytologically confirmed relapsed/refractory hematological malignancy or advanced/metastatic solid cancer Measurable disease Have had all available therapeutic standards for their disease Willingness to undergo baseline biopsy/bone marrow aspiration in case biopsy was not collected after completion of the most recent prior therapy ECOG performance status ≤ 1 Life expectancy > 3 months as assessed by the investigator Acceptable clinical lab results Main Exclusion Criteria: Systemic steroids at a daily dose of > 10 mg of prednisone or equivalent within 28 days before study treatment. Transient use of steroids for other medical condition may be allowed Ongoing immune-related adverse events irAEs and or AEs ≥ grade 2 from previous therapies not resolved except vitiligo, stable neuropathy up to grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy Within 4 weeks of major surgery Documented history of active autoimmune disorder requiring systemic immunosuppressive therapy within the last 12 months Prior solid organ transplant Primary or secondary immune deficiency Active and uncontrolled infection requiring intravenous antibiotic or antiviral treatment Seropositive (except after vaccination or confirmed cure for hepatitis) for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) Clinically significant disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Monotherapy dose escalation followed by dose confirmation of combination regimens. Further expansion of each groups.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OT-A201 monotherapy<br>OT-A201 administered by IV infusion on a weekly (qw) basis. An alternative dosing schedule of every 2 weeks (q2w) may be implemented based on the clinical safety and laboratory data. | Drug: OT-A201<br>* OT-A201 IV infusion qw or q2w<br>|
| Experimental: OT-A201 in combination with iMiD<br>OT-A201 in combination with lenalidomide or pomalidomide at the approved dose | Drug: OT-A201<br>* OT-A201 IV infusion qw or q2w<br>Drug: IMids<br>* Combination regimen for hematological malignancy Lenalidomide: 25 mg on Days 1 to 21 of each 28-day cycle; or Pomalidomide: 4 mg on Days 1 to 21 of each 28-day cycle<br>* Other names: pomalidomide;|
| Experimental: OT-A201 in combination with a specific agent<br>OT-A201 in combination with late stage approved treatment (combination to be defined by a protocol amendment) | Drug: OT-A201<br>* OT-A201 IV infusion qw or q2w<br>Drug: TBD Compound<br>* Combination regimen for hematological malignancy<br>|
| Experimental: OT-A201 in combination with bevacizumab<br>OT-A201 in combination with bevacizumab at the approved dose | Drug: OT-A201<br>* OT-A201 IV infusion qw or q2w<br>Drug: Bevacizumab<br>* Combination regimen for solid tumor Bevacizumab: 10 mg/m² q2w<br>|
| Experimental: OT-A201 in combination with paclitaxel<br>OT-A201 in combination with paclitaxel at the approved dose | Drug: OT-A201<br>* OT-A201 IV infusion qw or q2w<br>Drug: Paclitaxel<br>* Combination regimen for solid tumor Paclitaxel: 175 mg/m² q3w<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose(s) (MTD) and recommended dose(s) of OT-A201 | Evaluate dose-limiting toxicity (DLT) during the DLT observation period | 28 days | 
| Safety profile of OT-A201 | Incidence, severity, and relationship of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs leading to discontinuation of study treatment; and clinically significant findings on clinical laboratory tests, vital signs, ECGs, and physical examinations | 6 months |