First-in-human Study of CRB-601-01 to Treat Patients With Advanced Solid Tumor.
brief summary
The purpose of this study is to determine the safety, blood concentrations and treatment effect of CRB-601 in combination with immunotherapy in patients who have advanced solid tumors (cancer) and have exhausted other therapeutic options.CRB-601 targets a protein called avb8 integrin which is expressed by some cancers and not others. This study will focus on tumor types which are know to highly or moderately express this protein. Researchers will evaluate the side effects caused by treatment, levels of CRB-601 in the blood, and the effect on the participant cancer. This will help researchers understand the right dose of CRB-601 to use for treatment and whether it is an effective treatment to combine with standard of care treatments such as immunotherapy. It will also help the researchers understand whether combining CRB-601 with standard-of-care immunotherapy and immune-priming radiotherapy is a safe and effective approach to treat cancer. Participants in the study will receive CRB-601 via an infusion every two weeks either alone or in combination with immunotherapy. There will be assessments to check on the participants general health status (including blood tests) and adverse effects. Participants will also receive regular CT or MRI scans to evaluate the effect of CRB-601 on their cancer. Participants will continue to visit the clinic every two weeks while they are receiving benefit from treatment. If their cancer progresses, participants will be asked to continue to be followed-up by the researchers to understand long-term outcomes, even if they receive other treatments.
detailed description
CRB-601-01 is a three-part interventional study which aims to:
* To determine the maximum tolerated dose (MTD) and pharmacologically active dose range (PADR) for CRB-601 administered as a monotherapy in patients with select relapsed/refractory solid tumors who have progressed after at least one line of therapy * To determine the optimized dose for CRB-601 when administered within the PADR in combination with anti-programmed (cell) death ligand 1 (anti-PD-(L)1) therapy ( in patients with select relapsed/refractory solid tumors who have progressed after at least one line of therapy * To determine the optimized dose for CRB-601 when administered within the PADR in combination with anti-PD(L)-1 therapy in patients with select relapsed/refractory solid tumors who have progressed after at least one line of therapy
The study will be run in 3 parts (A-C), run sequentially.
Part A Dose Escalation
Part A is designed to evaluate the safety, tolerability, and determine the MTD of CRB-601 administered as monotherapy in participants with select relapsed/refractory solid tumors that are known to express avb8 integrin. All participants will have had disease progression (PD) after at least one line of therapy or have no other standard therapy of proven clinical benefit currently available or be recommended based on the investigator's individual risk-benefit assessment for the participant.
In Part A, doses will be escalated following the standard Bayesian Optimal Interval Design (BOIN) to determine the MTD and PADR or CRB-601. Three (3) dose groups treated on a 28 cycle with dosing every 2 weeks (Q2W) are predetermined. The target toxicity level is 0.3, the maximum number of participants that can be enrolled at each dose level is 12 participants and the maximum sample size of the BOIN design is 36. Determination of dose-limiting toxicities (DLT) will be based on toxicities observed during the DLT observation period (first 28-days or Cycle 1). Dose escalation /de-escalation decisions are made on the basis of occurrence of DLT.
Part B Combination Safety Lead-in and Signal Seeking
Part B is designed to assess the safety and tolerability of CRB-601 combined with anti-PD(L)-1 therapy. There will be two distinct phases to Part B, a safety lead-in phase with a two-step dose-escalation and an Expansion Phase to seek efficacy signals in select solid tumors. The following cohorts will be initiated:
official title
A Phase 1/2 Study to Investigate the Safety, Pharmacokinetics and Efficacy of CRB-601, a Monoclonal Antibody Against Integrin avb8, in Patients With Advanced Solid Tumors