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

Sponsor

Onward Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05828459

Collaborator

(none)

150

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hematological Malignancy Solid Tumor	Drug: OT-A201 Drug: IMids Drug: Bevacizumab Drug: Paclitaxel Drug: TBD Compound	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Monotherapy dose escalation followed by dose confirmation of combination regimens. Further expansion of each groups.Monotherapy dose escalation followed by dose confirmation of combination regimens. Further expansion of each groups.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2027

Anticipated Study Completion Date :

Jul 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OT-A201 monotherapy 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 OT-A201 IV infusion qw or q2w
Experimental: OT-A201 in combination with iMiD OT-A201 in combination with lenalidomide or pomalidomide at the approved dose	Drug: OT-A201 OT-A201 IV infusion qw or q2w Drug: IMids 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 Other Names: lenalidomide pomalidomide
Experimental: OT-A201 in combination with a specific agent OT-A201 in combination with late stage approved treatment (combination to be defined by a protocol amendment)	Drug: OT-A201 OT-A201 IV infusion qw or q2w Drug: TBD Compound Combination regimen for hematological malignancy
Experimental: OT-A201 in combination with bevacizumab OT-A201 in combination with bevacizumab at the approved dose	Drug: OT-A201 OT-A201 IV infusion qw or q2w Drug: Bevacizumab Combination regimen for solid tumor Bevacizumab: 10 mg/m² q2w
Experimental: OT-A201 in combination with paclitaxel OT-A201 in combination with paclitaxel at the approved dose	Drug: OT-A201 OT-A201 IV infusion qw or q2w Drug: Paclitaxel Combination regimen for solid tumor Paclitaxel: 175 mg/m² q3w

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose(s) (MTD) and recommended dose(s) of OT-A201 [28 days]
Evaluate dose-limiting toxicity (DLT) during the DLT observation period
Safety profile of OT-A201 [6 months]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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