A Phase I/II Study to Investigate the Safety, Pharmacokinetics and Efficacy of CRB-601, a Monoclonal Antibody Against Integrin avb8, in Patients With Advanced Solid Tumors

Study Identifier:
CRB-601-01
CT.gov Identifier:
NCT06603844
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

The purpose of this study is to determine the safety, blood concentrations and treatment effect of CRB-601 in combination with immunotherapy or immune-priming radiotherapy 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\'s 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 and immune-priming radiotherapy. For patients receiving the immune-priming radiotherapy they will receive three doses of radiotherapy focused on a single tumor.

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.

To investigate the safety, pharmacokinetics, and efficacy of CRB-601 in patients with advanced solid tumors

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Part A: Dose 1 CRB-601 monotherapy
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  • Drug: Experimental: Part A: Dose 2 of CRB-601 monotherapy
  • Drug: Experimental: Part A: Dose 3 of CRB-601 monotherapy
  • Drug: Experimental: Part B/Cohort 1: Dose level (low) CRB-601 in combination with anti-PD(L)-1
  • Drug: Drug: Anti-PD-1 monoclonal antibody
  • Drug: Experimental: Part B/Cohort 2: Dose level (high) CRB-601 in combination with anti-PD(L)-1
  • Drug: Experimental: Part B/Expansion: Dose level (defined in Part B/ Safety Le) CRB-601 in combination with anti-PD(L)-1
  • Drug: Experimental: Part C - Low dose CRB-601 in combination with anti-PD(L)-1
  • Drug: Experimental: Part C - High dose CRB-601 in combination with anti-PD(L)-1
  • Drug: Intervention/Treatment:
  • Drug: Radiation: Immune-priming single lesion SBRT
  • Drug: Part A Dose Escalation
  • Drug: 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.
  • Drug: 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.
  • Drug: Part B Combination Safety Lead-in and Signal Seeking
  • Drug: Part B is designed to assess the safety and tolerability of CRB-601 combined with anti-PD(L)-1 therapy, with or without single-lesion, immune-priming SBRT. 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:
  • Drug: Safety Lead-in
  • Drug: A cohort of 20 participants with select tumor-types (10 participants at a low-dose, and 10 participants at a high-dose, as selected in Part A) in combination with anti-PD(L)-1 at the recommended dose and schedule.
  • Drug: Part C Dose Optimization
  • Drug: Part C will follow a time-to-event Bayesian optimal Phase 2 (TOP Bayesian) study design developed for cancer immunotherapy. The aim of dose optimization is to determine the recommended Phase 2 dose (RP2D) by evaluating the efficacy of CRB-601 in combination with anti-PD(L)-1, with or without single-lesion, immune-priming SBRT (in terms of objective response rate [ORR]) when administered at two dose levels in a tumor-type selected based on preliminary efficacy observed in Part A and B. Participants will be randomized into one of two dose levels (low-dose CRB-601 group and high-dose CRB- 601 group) of 12-20 participants. In each arm, eligible participants will receive CRB-601 in combination with anti-PD(L)-1, with or without single lesion, immune priming SBRT (should the risk/benefit of immune-priming be established in Part B) and be monitored for safety and efficacy.
  • Drug: For all enrolled participants (Parts A to C), study intervention will continue until any of the pre-defined criteria for discontinuation of study intervention are met, including intolerable toxicity, death, withdrawal of consent for study intervention, start of a new anti-cancer therapy, or investigator determined PD according to RECIST 1.1 or symptomatic deterioration attributed to PD.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • * Confirmed diagnosis of select locally advanced or metastatic solid tumors that have progressed after at least one line of therapy or have no other standard therapy with proven clinical benefit available.
    • * Measurable disease on imaging as assessed by RECIST 1.1 Eastern Cooperative Oncology Group (ECOG) performance status (PS) greater or equal to 2.
    • * Life expectancy of more than 12 weeks.
    • * Adequate hematologic and end-organ function.
    Exclusion criteria
    • * History of solid tumor malignancies other than the disease under study within 3 years of study enrollment
    • * History of and/or current cardiovascular events or conditions
    • * Chronic severe liver disease or liver cirrhosis
    • * Systemic autoimmune disease
    • * Active thrombophlebitis, thromboembolism or hypercoagulability states or uncontrolled bleeding or diabetes.
    • * Interstitial lung disease within 6 months of study enrollment.
    • * Active or persistent infection
    • * Other conditions that in the opinion of the Investigator would compromise the outcomes of the study.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START San Antonio
    San Antonio, TX, United States, 78229
    Investigator
    Amita Patnaik
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Solid Tumor