This is a first-in-human (FIH), Phase 1/2, open-label, multicenter study to assess safety and determine the recommended Phase 2 dose (RP2D) of BOXR1030 administration after lymphodepleting chemotherapy (LD chemotherapy) in subjects with glypican-3 positive (GPC3+) advanced solid tumors.
This is a FIH, Phase 1/2, open-label, multicenter study to assess safety and determine the maximum tolerated dose (MTD) and/or RP2D of BOXR1030 administration after LD chemotherapy in subjects with GPC3+ advanced solid tumors. After signing informed consent and completing all screening assessments, eligible subjects will be enrolled and undergo leukapheresis to obtain T cells for BOXR1030 manufacturing. Subjects will receive a 3-day LD chemotherapy regimen with fludarabine and cyclophosphamide, administered according to institutional standard practice for these drugs, including inpatient administration as appropriate. Subjects must be hospitalized for BOXR1030 administration and will remain hospitalized for 10 days after the infusion. For 28 days after BOXR1030 administration, all subjects must stay within a distance that requires no more than 2 hours of travel to the study site. During the Post-treatment Evaluation Period (within 6 months after BOXR1030 administration), study visits will occur daily for the first week, twice in the second week, and then once weekly at Weeks 3, 4, 6, 9, 12, 15, 18, and 24. Safety (targeted physical examination, adverse event \[AE\] assessment, and clinical laboratory tests) will be evaluated and samples will be collected for endpoint analyses. For 28 days after BOXR1030 administration, subjects will be required to monitor their temperature and complete neurological evaluation via the immune effector cell-associated encephalopathy assessment tool every day (to be administered by site staff during clinical visits and by a caregiver at home on non-clinic days). At regular intervals, antitumor activity will be assessed per RECIST 1.1 and iRECIST criteria. After 6 months of follow-up from BOXR1030 administration, subjects will enter the Long-term Follow-up Period for a total duration of 15 years after BOXR1030 dosing. Study visits are scheduled at Months 7, 9, 11, 13, 15, 18, 21, and 24, every 6 months thereafter until Year 5, and then annually through Year 15. Long-term follow-up assessments will focus on long-term safety and disease status. Subjects whose disease does not progress before Week 24 will enter the Long-term Follow-up at Month 7. Survival status will be checked at these visits.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Five dose levels each with LD chemotherapy
Hoag Hospital Newport Beach
Newport Beach, California, United States
Baylor Scott and White Research Institute
Dallas, Texas, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Dose limiting toxicity
Defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or American Society for Transplantation and Cellular Therapy (ASTCT) criteria for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome.
Time frame: From the time of BOXR1030 administration (Study Day 1) through 28 days after BOXR1030 administration (Study Day 28/Week 4)
MTD
Defined as the dose that maximizes the probability of targeted toxicity among doses that satisfy the escalation with overdose control criterion.
Time frame: From the time of BOXR1030 administration (Study Day 1) through 28 days after BOXR1030 administration (Study Day 28/Week 4)
RP2D
The RP2D may be the same as the MTD, a previously tested dose, or an intermediate/alternative dose below the MTD that is yet unexplored. Alternatively, the RP2D may be selected on the basis of observed safety and activity in dose escalation before the MTD is reached.
Time frame: From the time of BOXR1030 administration (Study Day 1) through 28 days after BOXR1030 administration (Study Day 28/Week 4)
Treatment-emergent AEs (TEAEs)
Type, frequency, and severity of TEAEs; clinically significant abnormal safety laboratory findings; and vital signs. TEAEs and laboratory findings according to NCI CTCAE version 5.0 and ASTCT criteria.
Time frame: From the time of BOXR1030 administration (Study Day 1) through Week 24
Overall response rate
Defined according to RECIST 1.1 criteria.
Time frame: From the time of BOXR1030 administration (Study Day 1) until disease progression/recurrence or start of new anti-cancer therapy, whichever came first, assessed up to approximately 15 years
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Fred Hutchinson Cancer Center - Seattle Cancer Care Alliance (SCCA) Location
Seattle, Washington, United States
Froedtert and Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Beatson Institute for Cancer Research Wolfson Wohl Cancer Research Centre
Glasgow, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
The Royal Marsden NHS Foundation Trust
London, United Kingdom
Best overall response
Defined as the best response recorded from the date of treatment to disease progression or death.
Time frame: From the time of BOXR1030 administration (Study Day 1) until disease progression or death, whichever came first, assessed up to approximately 15 years
Duration of response
Defined as the time from the first achieved response (complete or partial) to the first date of radiological progression.
Time frame: From the date of response for patients with response (complete or partial) until disease progression or death, whichever came first, assessed up to approximately 15 years
Progression-free survival
Defined as the time from the date of treatment to the first date of radiological progression or death.
Time frame: From the time of BOXR1030 administration (Study Day 1) until disease progression or death, whichever came first, assessed up to approximately 15 years
Clinical benefit rate
Defined as the total number (or percentage) of patients who achieved a complete response, partial response, or had stable disease for 6 months or longer.
Time frame: From the time of BOXR1030 administration (Study Day 1) until disease progression or death, whichever came first, assessed up to approximately 15 years
Time to response
Defined as the time from the date of treatment to the first objective tumor response.
Time frame: From the time of BOXR1030 administration (Study Day 1) until response, assessed up to approximately 15 years
Time to progression
Defined as the time from the date of treatment to disease progression.
Time frame: From the time of BOXR1030 administration (Study Day 1) until disease progression, assessed up to approximately 15 years
BOXR1030 T-cell levels in blood
BOXR1030 T-cell levels in blood will be analyzed.
Time frame: From the time of BOXR1030 administration (Study Day 1) until the end of the study, assessed up to approximately 15 years
BOXR1030 T-cell characterization in blood
DNA samples will be analyzed to detect BOXR1030 transgene levels (GPC3 chimeric antigen receptor \[CAR\]). Peripheral blood mononuclear cells will be used to evaluate immune cell surface markers along with GPC3 CAR for characterization of BOXR1030 T cells in blood.
Time frame: From the time of BOXR1030 administration (Study Day 1) until the end of the study, assessed up to approximately 15 years
Levels of inflammatory markers
Inflammatory markers will include, e.g., ferritin, C-reactive protein, erythrocyte sedimentation rate, and triglycerides.
Time frame: From the time of BOXR1030 administration (Study Day 1) until the end of the study, assessed up to approximately 15 years