Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06603844
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-13
Brief Title:
First-in-human Study of CRB-601-01 to Treat Patients with Advanced Solid Tumor
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Phase 12 Study to Investigate the Safety Pharmacokinetics and Efficacy of CRB-601 a Monoclonal Antibody Against Integrin Avb8 in Patients with Advanced Solid Tumors
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 optionsCRB-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 participantampamp39s 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
Researchers will evaluate the side effects caused by treatment levels of CRB-601 in the blood and the effect on the participantampamp39s 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
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 relapsedrefractory 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-L1 therapy in patients with select relapsedrefractory 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-PDL-1 therapy and single-lesion immune-priming stereotactic body radiation therapy SBRT in patients with select relapsedrefractory 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 relapsedrefractory 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 investigators 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 03 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-PDL-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
Safety Lead-in
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-PDL-1 at the recommended dose and schedule
A second cohort of 20 participants will be treated with CRB-601 10 participants at a low dose and 10 participants at a high-dose in combination with anti-PDL-1 at the recommended dose and schedule and single-lesion immune-priming SBRT
Additional participants with select tumor-types showing preliminary efficacy will be enrolled in an expansions phase
Part C Dose Optimization
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-PDL-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-PDL-1 with or without single lesion immune priming SBRT should the riskbenefit of immune-priming be established in Part B and be monitored for safety and efficacy
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 11 or symptomatic deterioration attributed to PD
General
In all parts tumor response will be evaluated by the investigator according to RECIST v1 During the post-treatment follow-up period only participants who had discontinued study intervention for reasons other than PD or start of a new anti-cancer therapy eg due to toxicity will undergo tumor assessments In these participants tumor assessments will continue until death confirmed radiographic PD according to RECIST v11 symptomatic deterioration attributed to PD initiation of a subsequent anti cancer therapy withdrawal of consent for the study or any of the other pre defined criteria for withdrawal from the study are met whichever occurs first All discontinued participants with the exception of the reason of death will be followed for 3 months for immune-related adverse events irAEs unless consent is refused in writing by the participant Lesions selected for single lesion immune priming SBRT or on-treatment biopsy will be omitted from tumor assessments by RECIST v11 Clinical and laboratory adverse events AEs will be reported and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE v50 Guidelines for dose interruptions eg for toxicity are included in the protocol
Biomarkers will also be measured Collection of off- and on-treatment biopsies in Parts A to C are considered mandatory unless agreed with the sponsor Fresh tumor biopsies or archival tumor formalin fixed paraffin embedded FFPE samples are acceptable for baseline evaluation and on-treatment samples will be collected on C2D15 Blood samples for biomarker and cytokinechemokine assessments will also be collected
To determine the maximum tolerated dose MTD and pharmacologically active dose range PADR for CRB-601 administered as a monotherapy in patients with select relapsedrefractory 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-L1 therapy in patients with select relapsedrefractory 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-PDL-1 therapy and single-lesion immune-priming stereotactic body radiation therapy SBRT in patients with select relapsedrefractory 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 relapsedrefractory 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 investigators 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 03 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-PDL-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
Safety Lead-in
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-PDL-1 at the recommended dose and schedule
A second cohort of 20 participants will be treated with CRB-601 10 participants at a low dose and 10 participants at a high-dose in combination with anti-PDL-1 at the recommended dose and schedule and single-lesion immune-priming SBRT
Additional participants with select tumor-types showing preliminary efficacy will be enrolled in an expansions phase
Part C Dose Optimization
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-PDL-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-PDL-1 with or without single lesion immune priming SBRT should the riskbenefit of immune-priming be established in Part B and be monitored for safety and efficacy
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 11 or symptomatic deterioration attributed to PD
General
In all parts tumor response will be evaluated by the investigator according to RECIST v1 During the post-treatment follow-up period only participants who had discontinued study intervention for reasons other than PD or start of a new anti-cancer therapy eg due to toxicity will undergo tumor assessments In these participants tumor assessments will continue until death confirmed radiographic PD according to RECIST v11 symptomatic deterioration attributed to PD initiation of a subsequent anti cancer therapy withdrawal of consent for the study or any of the other pre defined criteria for withdrawal from the study are met whichever occurs first All discontinued participants with the exception of the reason of death will be followed for 3 months for immune-related adverse events irAEs unless consent is refused in writing by the participant Lesions selected for single lesion immune priming SBRT or on-treatment biopsy will be omitted from tumor assessments by RECIST v11 Clinical and laboratory adverse events AEs will be reported and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE v50 Guidelines for dose interruptions eg for toxicity are included in the protocol
Biomarkers will also be measured Collection of off- and on-treatment biopsies in Parts A to C are considered mandatory unless agreed with the sponsor Fresh tumor biopsies or archival tumor formalin fixed paraffin embedded FFPE samples are acceptable for baseline evaluation and on-treatment samples will be collected on C2D15 Blood samples for biomarker and cytokinechemokine assessments will also be collected
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None