IMX-110 in Patients With Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

A Phase 1/2a Open-Label, Dose-Escalation/Dose-Expansion Safety, Tolerability and Pharmacokinetic Study of IMX-110 in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03382340
• Other study ID #: IMX-110-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 15, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: September 2023
• Source: Immix Biopharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase 1 is an open-label, multi-center dose escalation/dose expansion study designed to assess the safety, tolerability and pharmacokinetics (PK) for the recommended phase 2 dose (RP2D) of IMX-110. The RP2D will be evaluated in a further dose expansion Phase 2a study submitted.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 70
• Est. completion date: December 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female patients who are 18 years or older

2. Patients with confirmed advanced solid tumor as per histology, who have progressed, are refractory, or are intolerant to standard therapy appropriate for tumor type

3. Patients with an Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2 (Appendix 2)

4. Patients with a life expectancy of at least 3 months

5. Patients with adequate cardiac function as measured by left ventricular ejection fraction >50%

6. Patients who meet the following laboratory requirements:

1. Absolute neutrophil count (ANC) = 1.0 x 10^9/L

2. Hemoglobin (HGB) = 90.0 g/L (patients may be transfused to achieve this HGB level)

3. Platelet count = 100 x 10^9/L

4. Total bilirubin level = 1.5 x ULN

5. AST and ALT = 2.5 x ULN (=5 x ULN if liver metastasis present)

6. Creatinine = 1.5 x ULN (Creatinine clearance >50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal)

7. Women of childbearing potential and men must agree to use highly effective, double barrier contraception during the study and for 6 weeks following the final dose of IMX-110. Double barrier contraception is defined as a condom AND one other form of the

following:

1. Birth control pills (The Pill)

2. Depot or injectable birth control

3. IUD (Intrauterine Device)

4. Birth control patch (e.g. Ortho Evra)

5. NuvaRing®

6. Documented evidence of surgical sterilization at least 6 months prior to the screening visit, i.e., tubal ligation or hysterectomy for women or vasectomy for men. Male patients must not donate sperm for at least 24 weeks post-dose of the last study treatment. Male partners of female patients and female partners of male patients must also use contraception, if they are of childbearing potential. Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1. Rhythm methods during the study and for 6 weeks after the dose of IMX-110 will not be acceptable.

Exclusion Criteria:

1. Patients with a history of severe allergic reactions to any unknown allergens or any components of the study drug formulation.

2. Patients receiving any chemotherapy within 14 days of dosing, immunotherapy within 28 days of dosing, or biologic or hormonal therapy within 28 days of dosing for cancer treatment. Patients with prostate cancer can continue administration of Gonadotropin-releasing hormone (GnRH) agonists.

3. Subject participating in any other drug study = 4 weeks (6 weeks for immunotherapy investigational agents) or 5 half-lives of the investigational product, whichever is longer, prior to study drug administration or is scheduled to receive one during the treatment or post-treatment period.

4. Patients who have reached their life time limit of DOX or who are anticipated to reach their lifetime limit (550 mg/m2) within the first 2 cycles of IMX-110 administration.

5. Patients who are expected to need surgery or benefit from other anti-cancer therapy to be initiated during the study period.

6. Patients with a history of and/or risk factors for ischemic heart disease, congestive heart failure, symptomatic bradycardia, atrioventricular (AV) block, prolonged QTcF interval (>450 msec in men and >470 msec in women and additional risk factors for QT prolongation (e.g. hyperthyroidism, electrolyte imbalance).

7. Patients who have not recovered from adverse events (AEs; = CTCAE grade 2) due to prior treatment (i.e. chemotherapy, targeted therapy, radiation, or surgery) within 7 days prior to Cycle 1 Day 1, unless deemed to be irreversible, or approved by the Sponsor and Medical Monitor.

8. Females who are pregnant or lactating or intend to become pregnant before, during, or within 24 weeks after participating in this study; or intending to donate ova during such time period.

9. Patients with a known positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C antibodies (HCV). Patients may be enrolled if they have HBV or HCV with viral load suppressed by anti-virals.

10. Any condition that, in the opinion of the investigator or sponsor, would interfere with evaluation of the investigational product.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Breast Cancer
• Neoplasms
• Ovarian Cancer
• Pancreatic Cancer
• Solid Tumor, Adult

Intervention

Drug:
• Imx-110
a nanoparticle encapsulating a Stat3/NF-kB/poly-tyrosine kinase inhibitor and low-dose doxorubicin

Locations

Country	Name	City	State
Australia	St George Hospital	Sydney	New South Wales
United States	Sarcoma Oncology Research Center	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Immix Biopharma Australia Pty Ltd

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacodynamic activity of IMX-110 with appropriate biomarkers.		Baseline and the end of Cycle 1 (each cycle is 28 days)
Primary	Number of participants with treatment-related adverse events assessed by CTCAE v4.03.		28 days
Primary	Maximum tolerated dose (MTD) of IMX-110 in patients with advanced solid tumors for evaluation in Phase 2a.	The MTD is defined as the highest dose at which = 33% of the patients treated during the 3+3 design experience a DLT and/or at least two = grade 2 toxicities during the first treatment cycle, and will be used to identify the RP2D to be taken forward to Phase 2a.	28 days
Primary	Recommended Phase 2 Dose (RP2D) of IMX-110 in patients with advanced solid tumors	RP2D is defined as one dose level below MTD	28 days
Secondary	Plasma concentrations of IMX-110	Plasma concentrations of IMX-110 will be measured when administered in treatment Cycle 1. Samples will be collected on the first day (pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose) and the 5th day of dosing (pre-dose, 0.5, 1, 2, 4 and 6 hours post-dose).	5 days
Secondary	Response Rate	Objective Response Rate as determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.	8 weeks
Secondary	Progression-free survival (PFS)	PFS is measured from the start of treatment to the time of progression or death, whichever occurs first while on the study.	5 years
Secondary	Overall Survival (OS)	OS is defined as the time from Cycle 1 Day1 to death due to any cause.	5 years
Secondary	Duration of Response (DOR)	DOR as determined by RECIST criteria version 1.1.	5 years