This is a phase IB/II, open-label study evaluating CTX-009 as monotherapy and in combination with CTX-471. The study evaluates the safety and efficacy of the monotherapy and the combination in patients with recurrent glioblastoma. The study tests the hypothesis that treatment with CTX-009 alone or in combination with CTX-471 will lead to enhanced tumor control and prolongation of overall survival of patients with recurrent glioblastoma.
CTX-009 expands on existing anti-angiogenic therapies by ablating key compensatory and resistance mechanisms to bevacizumab, CTX-471 restores local immune reactivity through activation of costimulatory immune mediators. Combination of these two agents may further impair tumor proliferation through synergistic effects on the tumor microenvironment
Histologically or radiographically confirmed recurrent CNS WHO grade 4 IDH wild-type glioma following standard of care treatment including radiation, chemotherapy, and/or tumor-treating fields. No more than 2 recurrences are allowed.
Patients may receive palliative treatment for recurrent disease prior to study enrollment with surgery or laser thermal ablation but must wait at least 4 weeks post-procedure to start study drug(s) and must have recovered from all procedure-related complications.
At least 18 years of age.
KPS performance status ≥ 60%
Have progressed on prior anti-VEGF-A therapy (i.e., bevacizumab) or developed clinically significant adverse reaction to any anti-VEGF therapy (i.e., bevacizumab, regorafenib) which led to discontinuation of treatment. Prior treatment with low dose anti-VEGF therapy for management of symptomatic vasogenic edema or radiation necrosis is permitted as long as progression was not noted while receiving treatment with the anti-VEGF agent, and is not needed for continued control of symptoms. A 4-week washout from last dose of low-dose anti-VEGF therapy is required.
Prior systemic anti-cancer therapy including: investigational agents or immunotherapy within 4 weeks (can consider 2 week interval for agents with known 5 half-lives <14 days following discussion with study PI); chemotherapy within 4 weeks (6 weeks for BCNU or CCNU); or targeted therapy within 2 weeks prior to treatment.
Use of aspirin, NSAIDs, or other antiplatelet agents within 7 days of study drug(s) initiation. Regular use (i.e., daily) of these agents should be avoided while on study treatment.
Use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes within 7 days of study drug(s) initiation. Prophylactic dosing of DOAC, such as apixaban or edoxaban, or LMWH for patency of venous access devices is allowed (preference is given to DOAC over LMWH).
Sequential
CTX-009
DrugCTX-009 will be given intravenously over the course of 60 minutes (+/- 5 minutes) on an outpatient basis every 2 weeks of a 28-day cycle.
CTX-471
DrugCTX-471 will be given intravenously over the course of 30 minutes (-5/+10) on an outpatient basis every 2 weeks of a 28-day cycle.
Phase IB Arm 1: Toxicity as measured by number of participants with adverse events
Adverse events will be graded according to CTCAE v6.0
Phase IB Arm 1: Recommended Phase 2 Dose (RP2D)
RP2D will be determined from the phase IB portion of Arm 1 by assessing tolerability. Tolerability is defined as ≤1 among patients experiencing excessive dose limiting toxicities (DLTs). The dose level in phase IB determined to be tolerable is the RP2D.
Phase IB Arm 2: Toxicity as measured by number of participants with adverse events
Adverse events will be graded according to CTCAE v6.0
Phase II Arm 1: Overall survival rate at 12 months (OS12)
Overall survival is defined from time of treatment start to time of death due to any cause or latest follow-up, whichever is earlier, with an inference focus on 12-month overall survival.
Overall response rate (ORR)
Overall Response Rate (ORR) is measured as the proportion of patients with complete response (CR) or partial response (PR) as defined by the RANO Response criteria. CR is defined as disappearance of all enhancing measurable and non-measurable disease for at least 4 weeks, no new lesions, stable or improved non-enhancing (T2/FLAIR) lesions, off corticosteroids and stable or improved clinically. PR is defined as ≥ 50% decrease of all measurable enhancing lesions for at least 4 weeks, no progression of non-measurable disease, stable or improved non-enhancing (T2/FLAIR) lesions, corticosteroid dose no greater than dose at time of baseline scan, stable or improved clinically
Duration of response (DoR)
DoR is defined as time from Day 1 of study treatment (CTX-009 with our without CTX-471) to disease progression or death in patients who achieve a complete response (CR) or partial response (PR) as defined by the RANO criteria. CR is defined as disappearance of all enhancing measurable and non-measurable disease for at least 4 weeks, no new lesions, stable or improved non-enhancing (T2/FLAIR) lesions, off corticosteroids and stable or improved clinically. PR is defined as ≥ 50% decrease of all measurable enhancing lesions for at least 4 weeks, no progression of non-measurable disease, stable or improved non-enhancing (T2/FLAIR) lesions, corticosteroid dose no greater than dose at time of baseline scan, stable or improved clinically. .
Median progression-free survival (mPFS)
mPFS is defined as the time of treatment start to the event of disease progression. Disease progression is measured based on the RANO criteria.
Median overall survival (mOS)
mOS is measured as the amount of time from treatment start to death due to any cause or latest follow up, whichever is earlier.
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Washington University School of Medicine
Lead sponsor
Compass Therapeutics
Collaborator
