NM32-2668 in Adult Patients With Selected Advanced Solid Tumors

March 1, 2024 updated by: Numab Therapeutics AG

A Phase 1 Study of NM32-2668 (Anti-ROR1/CD3/Anti-HSA Tri-Specific Antibody) in Adult Patients With Selected Advanced Solid Tumors

This is a first-in-human, open-label, multi-center, Phase 1, dose-escalation study with expansion cohorts to evaluate NM32-2668 for safety and immunogenicity, to determine the maximal tolerated dose and recommended Phase 2 dose, define the pharmacokinetics, to explore the pharmacodynamics, and to obtain preliminary evidence of the clinical activity in adult patients with selected advanced solid tumors.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

180

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Lifespan Cancer Institute at Rhode Island Hospital
        • Principal Investigator:
          • Benedito A. Carneiro, MD
        • Contact:
          • Benedito A. Carneiro, MD
    • Texas
      • Dallas, Texas, United States, 75230
        • Recruiting
        • Mary Crowley Cancer Research
        • Contact:
          • Douglas W. Orr, MD
        • Principal Investigator:
          • Douglas W. Orr, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with histologically confirmed, advanced-stage protocol-specified solid tumors.
  • Confirmed ROR1 tumor expression.
  • Patients who have undergone at least one prior systemic therapy and have radiologically or clinically determined progressive disease during or after most recent line of therapy, and for whom no further standard therapy is available, or who are intolerable or have medical contraindications to standard therapy.

Exclusion Criteria:

  • Prior treatment with any agent targeting ROR1 or prior treatment with a CD3 T-cell engaging therapy.
  • Prior treatment with chimeric antigen receptor (CAR) cell therapy within 90 days prior to first dose of NM32-2668.
  • Systemic anti-neoplastic therapy within five half-lives or 21 days, whichever is shorter, prior to first dose of NM32-2668.
  • Wide-field radiotherapy (> 30% of marrow-bearing bones) within 28 days, or focal radiation for analgesic purpose or for lytic lesions at risk of fracture within 14 days prior to first dose of NM32-2668, or no recovery from side effects of such prior interventions.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NM32-2668
Biological: NM32-2668
Anti-ROR1/Anti-Cluster of Differentiation 3 (CD3)/Anti-Human Serum Albumin (HSA) Tri-Specific Antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of Dose Limiting Toxicities (DLTs)
Time Frame: Through 28 days post-infusion
Through 28 days post-infusion
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) as assessed by CTCAE v5.0 / ASTCT (for Cytokine Release Syndrome [CRS])
Time Frame: Through 50 days post-final dose administration
Through 50 days post-final dose administration
Frequency of dose interruptions/reductions
Time Frame: Up to 12 treatment cycles or through treatment discontinuation, whichever occurs first
Up to 12 treatment cycles or through treatment discontinuation, whichever occurs first
Duration of dose interruptions/reductions
Time Frame: Up to 12 treatment cycles or through treatment discontinuation, whichever occurs first
Up to 12 treatment cycles or through treatment discontinuation, whichever occurs first

Secondary Outcome Measures

Outcome Measure
Time Frame
Assessment of the maximum observed serum concentration (Cmax)
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Assessment of the the minimum observed serum concentration (Cmin)
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Time from dosing at which maximum observed serum concentration is apparent (Tmax)
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Assessment of the terminal phase (apparent elimination) rate constant (λz)
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Assessment of the elimination half-life (t½)
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Assessment of the area under the serum concentration-time curve extrapolated from the last quantifiable concentration to infinity (AUC[0-infinity])
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Assessment of the area under serum concentration-time curve over dosing interval (AUCtau)
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Assessment of clearance (CL) of NM32-2668 in serum
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Assessment of the volume of distribution (Vd) of NM32-2668 in serum
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Assessment of accumulation ratios of Cmax (ARcmax) of NM32-2668 in serum
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Assessment of accumulation ratios of Cmin (ARcmin) of NM32-2668 in serum
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Assessment of accumulation ratios of AUC (ARauc) of NM32-2668 in serum
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Frequency of specific anti-drug antibodies (ADAs) to NM32-2668
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Concentration of specific ADAs to NM32-2668
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Incidence of specific ADAs by category to NM32-2668
Time Frame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Best Overall Response (BOR) according to RECIST 1.1
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed for up to 30 days following last dose of study treatment
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed for up to 30 days following last dose of study treatment
Overall Response Rate (ORR) according to RECIST 1.1
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed for up to 30 days following last dose of study treatment
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed for up to 30 days following last dose of study treatment
Disease Control Rate (DCR) according to RECIST 1.1
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed for up to 30 days following last dose of study treatment
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed for up to 30 days following last dose of study treatment
Progression-free Survival (PFS) according to RECIST 1.1
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion (on average, 1 year after last treatment)
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion (on average, 1 year after last treatment)
Time to Response (TTR) according to RECIST 1.1
Time Frame: From date of randomization until the date of first documented treatment response according to RECIST 1.1
From date of randomization until the date of first documented treatment response according to RECIST 1.1
Duration of Response (DOR) according to RECIST 1.1
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion (on average, 1 year after last treatment)
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion (on average, 1 year after last treatment)
Overall Survival (OS)
Time Frame: From date of randomization until the date of death from any cause, assessed through study completion (on average, 1 year after last treatment)
From date of randomization until the date of death from any cause, assessed through study completion (on average, 1 year after last treatment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Numab Therapeutics AG

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 29, 2024

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

February 26, 2024

First Submitted That Met QC Criteria

March 1, 2024

First Posted (Actual)

March 7, 2024

Study Record Updates

Last Update Posted (Actual)

March 7, 2024

Last Update Submitted That Met QC Criteria

March 1, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NB-NM032-2668-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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