Advanced and/or Metastatic Solid Tumors Known to Express B7-H3
Conditions
Keywords
Advanced solid tumor, Advanced metastatic tumor
Brief summary
This is a Phase 1a/1b, multicenter, open-label, first-in-human (FIH) study with MX006 treatment in patients with selected tumor types known to express B7-H3. The study will include 2 parts: * Dose-escalation (Part A) * Dose-expansion (Part B) A maximum of 120 patients may be enrolled in this study. The primary objective of the dose escalation (PART A) is to evaluate the safety and tolerability of MX006 and determine the maximum-tolerated dose (MTD) and the recommended doses for expansion (RDE) in patients with selected solid tumors; whereas the primary objective of the dose expansion (PART B) is to evaluate the safety and tolerability of MX006 at the dose level (s) recommended in Part A.
Interventions
DRUGMX006
Anti-B7-H3 ADC
Sponsors
Myricx Pharma Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients aged 18 years-or older at the time of signature of the informed consent form. * Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST v1.1 or the Prostate Cancer Clinical Trials Working Group 3 (for mCRPC only) as per Investigator discretion. Note: Patients with mCRPC can be enrolled without measurable disease but must have a minimum of 2 bone lesions and increased PSA. * Histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumors in patients with relapsed or refractory solid tumors known to express B7-H3 who have failed available standard therapy or who are not candidates for standard therapy. * Has adequate bone marrow and organ function within 7 days before the start of study * Has an adequate treatment washout period prior to start of study treatment, defined as: * Major surgery: ≥4 weeks (or 2 weeks for low-invasive cases \[e.g., colostomy\]). Note: major surgery is defined for example as a surgical procedure that is complex, invasive (e.g., enters a body cavity), is associated with higher risk of complications, and may require general anesthesia and hospitalization. * Radiation therapy: ≥4 weeks (if palliative single site stereotactic radiation therapy, ≥2 weeks.)
Exclusion criteria
* Prior treatment with an NMT inhibitor or any antibody-drug conjugate (ADC) that delivers an NMTi payload. * Has other invasive malignancy within 2 years; prior or concurrent non-invasive malignancies (with the exception of the following: in situ carcinomas of the cervix, non-melanoma skin cancers) and/or patients with localized malignancies that were treated with curative intent (e.g., localized breast cancer) who remain disease-free and are considered low likelihood for recurrence who may be enrolled on a case-by-case basis after discussion with the Medical Monitor). * Have clinically significant cardiac disease, known congestive heart failure (New York Heart Association classes II-IV) or a serious cardiac arrhythmia requiring treatment, and/ or a known decreased cardiac ejection fraction of \< 45%. A baseline QT interval as corrected by Fridericia's formula (QTcF) \> 470 msec, a complete left bundle branch block (defined as a QRS interval ≥ 120 msec in left bundle branch block form) or an incomplete left bundle branch block based on the average of triplicate 12-lead electrocardiogram (ECG) per local read. * Received any of the following within the specified time frame prior to administration of study treatment: Any systemic agent from a previous treatment regimen or clinical study including anti-cancer chemotherapy or small molecule ≤14 days or 5 half-lives (whichever is shorter); any biologic or hormonal agent ≤28 days or 5 half-lives (whichever is shorter). * Received any of the following within the specified time frame prior to administration of study treatment: Platelet transfusion, red blood cell transfusion and/or granulocyte colony-stimulating factor administration \< 1 week prior to screening assessments. Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) for patients treated with MX006 | From ICF signature until 30 days (AEs) and 90 days (SAEs) after last dose of MX006 | Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) will be graded according to Common Terminology Criteria for Adverse Events (version 6) |
| Number of participants who experience a clinically significant change from baseline safety laboratory values | Collected from screening until end of treatment and 30 days follow-up | Change from baseline |
| Frequency of dose interruptions and dose reductions for patients treated with MX006. | From first dose until last dose, up to 1 year | Frequency of dose interruptions and dose reductions for patients treated with MX006. |
| Incidence of dose limiting toxicities (DLTs) (dose-escalation only) for patients treated with MX006. | DLTs are collected during the first treatment cycle (21 days) | DLTs are dose-limiting toxicities as defined in the study protocol. |
| Number of participants who experience a clinically significant change from baseline in Eastern Cooperative Group Oncology (ECOG) performance status | Collected from screening until end of treatment and 30 days follow-up | Measured on a scale of from grades 0-5. |
| Number of participants who experience a clinically significant change from baseline in 12-lead electrocardiograph (ECG) measurements | Collected from screening until end of treatment and 30 days follow-up | — |
| Number of participants who experience a clinically significant change from baseline in blood pressure (vital signs) | Collected from screening until end of treatment and 30 days follow-up | Measured in mm Hg |
| Number of participants who experience a clinically significant change from baseline in heart rate (vital signs) | Collected from screening until end of treatment and 30 days follow-up | Measured in beats per minutes |
| Number of participants who experience a clinically significant change from baseline in respiratory rate (vital signs) | Collected from screening until end of treatment and 30 days follow-up | Measured in breaths per minute |
| Number of participants who experience a clinically significant change from baseline in body temperature (vital signs) | Collected from screening until end of treatment and 30 days follow-up | Measured in degrees Celsius |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the preliminary anti-tumor activity of MX006 | From screening until end of treatment, up to 1 year (follow-up for patients who discontinue treatment for reasons other than disease progression or initiation of other cancer therapy: 6 months (Part A) or 12 months (Part B) | Overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) |
| Overall survival (OS) | Through study completion, up to 48 months | Overall survival (OS) defined as the time between the start of treatment and death from any cause for patients treated with MX006. |
| Area under concentration time curve (AUC) | Day 1 to end of treatment, up to approximately 1 year | PK parameter |
| Maximum concentration of MX006 (Cmax) | Day 1 to end of treatment, up to approximately 1 year | PK parameter |
| Minimum concentration of MX006 (Cmin) | Day 1 to end of treatment, up to approximately 1 year | PK parameter |
| Time to maximum concentration of MX006 (Tmax) | Day 1 to end of treatment, up to approximately 1 year | PK parameter |
| Concentration of MX006 prior to next dose (Ctrough) | Day 1 to end of treatment, up to approximately 1 year | PK parameter |
| Terminal half-life of MX006 (t1/2) | Day 1 to end of treatment, up to approximately 1 year | PK parameter |
| Clearance of MX006 (CL) | Day 1 to end of treatment, up to approximately 1 year | PK parameter |
| Anti-drug antibody (ADA) response to MX006 | Day 1 to end of treatment, up to approximately 1 year | Frequency of confirmed positive anti-drug antibody (ADA) responses, and, if applicable, neutralizing activity to MX006 after treatment with MX006 |
Countries
United States
Contacts
CONTACTMyricx Pharma Contact for Clinical Trial Information
CONTACTMyricx Pharma Contact for Clinical Trial Information (Back-up)
STUDY_DIRECTORSteen Lisby, MD
Myricx Pharma
Outcome results
None listed