Adenocarcinoma - Gastroesophageal Junction (GEJ), Adenocarcinoma of Lung, Adenocarcinoma of the Stomach, Endometrial Cancer, Fallopian Tube Carcinoma, Leiomyosarcoma, Liposarcoma, Melanoma, Malignant, Mesothelioma, Malignant, Ovarian Carcinoma, Peritoneal Carcinoma, Renal Cell Carcinoma, Triple Negative Breast Cancer
Conditions
Brief 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.
Interventions
BIOLOGICALNM32-2668
Anti-ROR1/Anti-Cluster of Differentiation 3 (CD3)/Anti-Human Serum Albumin (HSA) Tri-Specific Antibody
Sponsors
Numab Therapeutics AG
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Dose Limiting Toxicities (DLTs) | 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]) | Through 50 days post-final dose administration |
| Frequency of dose interruptions/reductions | Up to 12 treatment cycles or through treatment discontinuation, whichever occurs first |
| Duration of dose interruptions/reductions | Up to 12 treatment cycles or through treatment discontinuation, whichever occurs first |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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) |
| 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 |
| 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) |
| 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) |
| 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 |
| 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 |
| 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 |
| Assessment of the terminal phase (apparent elimination) rate constant (λz) | From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation |
Countries
United States
Outcome results
None listed