Clinical trial NCT06299163: NM32-2668 in Adult Patients With Selected Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Ovarian Carcinoma
Fallopian Tube Carcinoma
Peritoneal Carcinoma
Endometrial Cancer
Adenocarcinoma of Lung
Triple Negative Breast Cancer
Liposarcoma
Leiomyosarcoma
Mesothelioma, Malignant
Adenocarcinoma - Gastroesophageal Junction (GEJ)
Adenocarcinoma of the Stomach
Melanoma, Malignant
Renal Cell Carcinoma
Lead sponsor: Numab Therapeutics AG
Sponsor class: INDUSTRY
First posted: 2024-03-07
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs)
timeFrame: Through 28 days post-infusion
measure: 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])
timeFrame: Through 50 days post-final dose administration
measure: Frequency of dose interruptions/reductions
timeFrame: Up to 12 treatment cycles or through treatment discontinuation, whichever occurs first
measure: Duration of dose interruptions/reductions
timeFrame: Up to 12 treatment cycles or through treatment discontinuation, whichever occurs first
Secondary outcomes:
measure: Assessment of the maximum observed serum concentration (Cmax)
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Assessment of the the minimum observed serum concentration (Cmin)
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Time from dosing at which maximum observed serum concentration is apparent (Tmax)
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Assessment of the terminal phase (apparent elimination) rate constant (λz)
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Assessment of the elimination half-life (t½)
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Assessment of the area under the serum concentration-time curve extrapolated from the last quantifiable concentration to infinity (AUC[0-infinity])
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Assessment of the area under serum concentration-time curve over dosing interval (AUCtau)
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Assessment of clearance (CL) of NM32-2668 in serum
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Assessment of the volume of distribution (Vd) of NM32-2668 in serum
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Assessment of accumulation ratios of Cmax (ARcmax) of NM32-2668 in serum
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Assessment of accumulation ratios of Cmin (ARcmin) of NM32-2668 in serum
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Assessment of accumulation ratios of AUC (ARauc) of NM32-2668 in serum
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Frequency of specific anti-drug antibodies (ADAs) to NM32-2668
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Concentration of specific ADAs to NM32-2668
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Incidence of specific ADAs by category to NM32-2668
timeFrame: From date of randomization until end of treatment, assessed for up to 336 days (i.e., 12 treatment cycles) or through treatment discontinuation
measure: Best Overall Response (BOR) according to RECIST 1.1
timeFrame: 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
measure: Overall Response Rate (ORR) according to RECIST 1.1
timeFrame: 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
measure: Disease Control Rate (DCR) according to RECIST 1.1
timeFrame: 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
measure: Progression-free Survival (PFS) according to RECIST 1.1
timeFrame: 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)
measure: Time to Response (TTR) according to RECIST 1.1
timeFrame: From date of randomization until the date of first documented treatment response according to RECIST 1.1
measure: Duration of Response (DOR) according to RECIST 1.1
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: From date of randomization until the date of death from any cause, assessed through study completion (on average, 1 year after last treatment)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Chicago
country: United States
facility: The University of Chicago Medical Center (UCMC)
state: Illinois
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan Cancer Institute at Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
Study officials:
References: