NM32-2668 in Adult Patients With Selected Advanced Solid Tumors

Endometrial Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06299163
• Other study ID #: NB-NM032-2668-101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 29, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: March 2024
• Source: Numab Therapeutics AG
• Contact: Martin Stern, MD
• Phone: +41 44 533 2292
• Email: clinicaltrials[@]numab.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Adenocarcinoma of the Stomach
• Carcinoma
• Endometrial Cancer
• Endometrial Neoplasms
• Fallopian Tube Carcinoma
• Leiomyosarcoma
• Liposarcoma
• Melanoma
• Melanoma, Malignant
• Mesothelioma
• Mesothelioma, Malignant
• Ovarian Carcinoma
• Peritoneal Carcinoma
• Renal Cell Carcinoma
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Biological:
• NM32-2668
Anti-ROR1/Anti-Cluster of Differentiation 3 (CD3)/Anti-Human Serum Albumin (HSA) Tri-Specific Antibody

Locations

Country	Name	City	State
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Lifespan Cancer Institute at Rhode Island Hospital	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Numab Therapeutics AG

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities (DLTs)		Through 28 days post-infusion
Primary	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])		Through 50 days post-final dose administration
Primary	Frequency of dose interruptions/reductions		Up to 12 treatment cycles or through treatment discontinuation, whichever occurs first
Primary	Duration of dose interruptions/reductions		Up to 12 treatment cycles or through treatment discontinuation, whichever occurs first
Secondary	Assessment of the maximum observed serum concentration (Cmax)		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Assessment of the the minimum observed serum concentration (Cmin)		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Time from dosing at which maximum observed serum concentration is apparent (Tmax)		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Assessment of the terminal phase (apparent elimination) rate constant (?z)		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Assessment of the elimination half-life (t½)		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Assessment of the area under the serum concentration-time curve extrapolated from the last quantifiable concentration to infinity (AUC[0-infinity])		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Assessment of the area under serum concentration-time curve over dosing interval (AUCtau)		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Assessment of clearance (CL) of NM32-2668 in serum		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Assessment of the volume of distribution (Vd) of NM32-2668 in serum		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Assessment of accumulation ratios of Cmax (ARcmax) of NM32-2668 in serum		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Assessment of accumulation ratios of Cmin (ARcmin) of NM32-2668 in serum		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Assessment of accumulation ratios of AUC (ARauc) of NM32-2668 in serum		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Frequency of specific anti-drug antibodies (ADAs) to NM32-2668		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Concentration of specific ADAs to NM32-2668		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Incidence of specific ADAs by category to NM32-2668		From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
Secondary	Best Overall Response (BOR) according to RECIST 1.1		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
Secondary	Overall Response Rate (ORR) according to RECIST 1.1		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
Secondary	Disease Control Rate (DCR) according to RECIST 1.1		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
Secondary	Progression-free Survival (PFS) according to RECIST 1.1		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)
Secondary	Time to Response (TTR) according to RECIST 1.1		From date of randomization until the date of first documented treatment response according to RECIST 1.1
Secondary	Duration of Response (DOR) according to RECIST 1.1		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)
Secondary	Overall Survival (OS)		From date of randomization until the date of death from any cause, assessed through study completion (on average, 1 year after last treatment)