Ignite Creation Date:
2024-05-11 @ 8:31 AM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06400160
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-06
First Post:
2024-04-01
Brief Title:
Clinical Trial of TB511 in Advanced Solid Tumors
Sponsor:
Twinpig Biolab Inc
Organization:
Twinpig Biolab Inc
Study Overview
Official Title:
Phase IIIa Clinical Trial to Assess the Maximum Tolerated Dose MTD Safety and the Anti-tumor Effect of TB511 Monotherapy and Pembrolizumab Combination Therapy in Patients With Advanced Solid Tumors
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
1 Study population TB511 Monotherapy Cohort for Phase I and Phase IIa Clinical Trial Participants with an advanced solid tumor who are either refractory or intolerant to standard of care SoC
Immune checkpoint inhibitors ICIs Combination Therapy Cohort for Phase IIa Clinical Trial Participants with advanced solid tumor who have either not responded to or have relapsed after ICIs that are anti-PD-1 or PD-L1 inhibitors and who have no standard of care available
2 Objectives of the Clinical Trial Phase I Clinical Trial 1 Primary Objective
To evaluate the safety and tolerability of TB511 monotherapy in Participants with advanced solid tumor to determine maximum tolerated dose MTD and recommended Phase IIa dose RP2D
2 Secondary Objectives
To evaluate the safety of TB511 monotherapy
To evaluate the objective response rate ORR and anti-tumor effect based on Response Evaluation Criteria in Solid Tumors Version 11 RECIST v11 of TB511 monotherapy
To evaluate the pharmacokinetic characteristics of TB511 monotherapy 3 Exploratory Objectives
To compare the changes in biomarker levels of TB511 monotherapy
To evaluate immunogenicity by measuring anti-drug antibodies against TB511 Phase IIa Clinical Trial
1 Primary Objective
To evaluate the ORR of TB511 monotherapy and combination therapy with Pembrolizumab in Participants with advanced solid tumors based on RECIST v11
2 Secondary Objectives
To evaluate the disease control rate DCR duration of response DoR and progression-free survival PFS of TB511 monotherapy and combination therapy with Pembrolizumab
To evaluate the safety and tolerability of TB511 monotherapy and combination therapy with Pembrolizumab
To evaluate the pharmacokinetic characteristics of TB511 monotherapy and combination therapy with Pembrolizumab
3 Exploratory Objectives
To compare the changes in biomarker levels of TB511 monotherapy
To evaluate immunogenicity by measuring anti-drug antibodies against TB511
Immune checkpoint inhibitors ICIs Combination Therapy Cohort for Phase IIa Clinical Trial Participants with advanced solid tumor who have either not responded to or have relapsed after ICIs that are anti-PD-1 or PD-L1 inhibitors and who have no standard of care available
2 Objectives of the Clinical Trial Phase I Clinical Trial 1 Primary Objective
To evaluate the safety and tolerability of TB511 monotherapy in Participants with advanced solid tumor to determine maximum tolerated dose MTD and recommended Phase IIa dose RP2D
2 Secondary Objectives
To evaluate the safety of TB511 monotherapy
To evaluate the objective response rate ORR and anti-tumor effect based on Response Evaluation Criteria in Solid Tumors Version 11 RECIST v11 of TB511 monotherapy
To evaluate the pharmacokinetic characteristics of TB511 monotherapy 3 Exploratory Objectives
To compare the changes in biomarker levels of TB511 monotherapy
To evaluate immunogenicity by measuring anti-drug antibodies against TB511 Phase IIa Clinical Trial
1 Primary Objective
To evaluate the ORR of TB511 monotherapy and combination therapy with Pembrolizumab in Participants with advanced solid tumors based on RECIST v11
2 Secondary Objectives
To evaluate the disease control rate DCR duration of response DoR and progression-free survival PFS of TB511 monotherapy and combination therapy with Pembrolizumab
To evaluate the safety and tolerability of TB511 monotherapy and combination therapy with Pembrolizumab
To evaluate the pharmacokinetic characteristics of TB511 monotherapy and combination therapy with Pembrolizumab
3 Exploratory Objectives
To compare the changes in biomarker levels of TB511 monotherapy
To evaluate immunogenicity by measuring anti-drug antibodies against TB511
Detailed Description:
1 Number of participants
Phase I Clinical Trial 3 to 6 participants per dose group Phase IIa Clinical Trial Approximately 20 participants per cohort Cohort 1 Approximately 20 participants Cohort 2 Approximately 20 participants
2 Study Duration
Total clinical trial duration Approximately 36 months from the IRB approval date however this may change depending on the time taken by participants to enroll Duration of participation of individual participants Screening period Up to 4 weeks 28 days Treatment period 1 cycle consists of 3 weeks 21 days and administration is continued until there are reasons to suspend administration
Safety follow-up period 6 weeks after the end of treatment EOT
3 Investigational Product
1 Study drug Product name or code TB511 Injection 8 mg Formulation and appearance White or off-white color of lyophilized powder Main ingredient TB511 Storage method Store in a hermetic container in a freezer -20 protect from light
2 Concomitant drug Product name or code Keytruda Formulation and appearance An injection comprised of clear to slightly opalescent colorless to slightly yellow liquid contained in a colorless and transparent vial
Main ingredient Pembrolizumab Storage method Store in a hermetic container refrigerated at 2 to 8 protect from light do not freeze
4 Dosage and method of administration
Phase I Clinical Trial
1 TB511 Initial dose 4 mg Dose escalation 4 mg 8 mg 16 mg 24 mg Administration method 1 cycle consists of 3 weeks 21 days Administer subcutaneously into the abdomen once every 7 days for 3 weeks 21 days Avoid repeat injection at the same site during subcutaneous injection and administer injections while changing the location within the same area abdomen In addition do not inject into the skin that is irritated or abnormal scar rash redness tenderness etc
Administration plan Administration is continued until intolerable toxicity verification of progressive disease PD under RECIST v11 or other reasons for discontinuing administration occur
Phase 2a Clinical Trial
1 TB511 Dose Recommended dose for Phase IIa determined in Phase I Administration method 1 cycle consists of 3 weeks 21 days Administer subcutaneously into the abdomen once every 7 days for 3 weeks 21 days Avoid repeat injection at the same site during subcutaneous injection and administer injections while changing the location within the same area abdomen In addition do not inject into the skin that is irritated or abnormal scar rash redness tenderness etc
Administration plan Administration is continued until intolerable toxicity verification of progressive disease PD under RECIST v11 or other reasons for discontinuing administration occur
2 Pembrolizumab Dose 200 mg or dose adjusted in accordance with the label Administration method Pembrolizumab is administered by continuous intravenous infusion for 30 minutes once every 3 weeks if pembrolizumab is administered with TB511 TB511 is administered at least 30 minutes after Pembrolizumab injection
Administration plan Administration is continued until intolerable toxicity verification of progressive disease PD under RECIST v11 or other reasons for discontinuing administration occur
5 Study Method
This clinical trial comprises a Phase I dose-escalation study to determine the maximum tolerated dose MTD of TB511 in participants with an advanced solid tumor who are either refractory or intolerant to standard of care and to determine the recommended Phase 2a dose RP2D and a Phase IIa study to verify the anti-tumor effect of TB511 monotherapy in dose determined in Phase I Cohort 1 and in combination with Pembrolizumab Cohort 2 in participants with an advanced solid tumor with no standard of care who have refractory or have relapsed after treatment with anti-PD-1 or PD-L1 ICIs
Participants who have voluntarily signed the written informed consent form undergo a screening test to verify eligibility of participation in this clinical trial during the screening period Participants who have been determined to be eligible in accordance with the inclusion and exclusion criteria are enrolled into this clinical trial and receive the determined dose of the investigational product 1 cycle of administration of the investigational product is 3 weeks 21 days and enrolled participants continue to receive the investigational product until intolerable toxicity verification of progressive disease PD under RECIST v11 or other reasons for discontinuing administration occur RECIST CTMRI is performed on Day 1 of cycle 1 and every 2 cycles thereafter Pharmacokinetic evaluation is performed on Day 1 and Day 21 of Cycle 1 and exploratory evaluation is conducted at the screening and Day 21 of Cycle 1
Phase I Clinical Trial TB511 Monotherapy Phase I clinical trial is conducted on a 3 3 basis beginning with the lowest-dose cohort until MTD is determined Depending on the method of determining MTD 3 to 6 participants are enrolled in the order for each dose level TB511 4 mg 8 mg 16 mg 24 mg with a minimum interval of 3 days and TB511 is administered for Cycle 1 in order to determine DLT DLT assessment is conducted in Cycle 1 and whether to escalate dose is determined by the Safety Review Committee SRC after the Cycle 1 DLT assessment has been completed for the last participant RP2D of Phase IIa clinical trial is determined through MTD and overall toxicity assessment
Phase IIa Clinical Trial Phase IIa clinical trial is conducted in approximately 20 participants with an advanced solid tumor for which there is no standard of care who is subject to TB511 monotherapy cohort Cohort 1 and approximately 20 participants with advanced solid tumor who have refractory or have relapsed after treatment with anti-PD-1 or ICIs that are PD-L1 inhibitors and for whom there is no standard of care who is subject to TB511 and Pembrolizumab combination therapy cohort Cohort 2
Cohort 1 TB511 Monotherapy Cohort For Cohort 1 participants are enrolled consecutively and treated with the RP2D dose of TB511 determined in the Phase I clinical trial
Cohort 2 TB511 and Pembrolizumab Combination Cohort For Cohort 2 the first 3 participants are enrolled serially with a minimum interval of 3 days and administered in combination of the RP2D dose of TB511 and Pembrolizumab for Cycle 1 to evaluate DLT If DLT occurs the 3 3 design is applied and the SRC thereby evaluate the safety of a total of 6 participants When DLT occurs in 2 out of 3 to 6 subjects the safety of combination therapy of a TB511 dose lower than the RP2D determined in Phase I and Pembrolizumab may be evaluated by the SRC in the same manner as above If the safety of combination therapy of TB511 and Pembrolizumab is determined per the decision of the SRC the remaining participants are simultaneously enrolled and participate in the clinical trial
Phase IIa Study Scheme
1 Definition and Assessment of Dose Limiting Toxicity DLT DLT is an adverse event or abnormal laboratory level unrelated to the progress of the disease or intercurrent disease that limits dose escalation and is consistent with one or more of the following criteria DLT assessment is conducted only at Cycle 1 after completion of Cycle 1 However even during Cycle 1 DLT can be immediately evaluated if toxicity is determined to be DLT DLT assessment is conducted in accordance with NCI-CTCAE v50 based on individual assessment items on hematologicalnon-hematological toxicity and other toxicities
6 Endpoints
1 Safety Endpoints Adverse Events Vital signs Physical examination Electrocardiogram Laboratory test
2 Primary endpoint Response Evaluation Criteria in Solid Tumors - RECIST Phase I Clinical Trial Solid tumor response is evaluated in accordance with RECIST v11 Objective response rate ORR Fraction of participants whose best overall response is Complete Response CR or Partial Response PR Disease control rate DCR Fraction of participants whose best overall response is CR PR or Stable Disease SD Duration of response DoR From the point of time when response occurs to CR or PR PD or death due to any reason
Phase IIa Clinical Trial Solid tumor response is evaluated in accordance with RECIST v11 and immune RECIST iRECIST
Objective response rate ORR Fraction of participants whose best overall response is CR or PR Disease control rate DCR Fraction of participants whose best overall response is CR PR or SD Duration of response DoR From the point of time when response occurs to CR or PR PD or death due to any reason
Progression-free survival PFS period Period from the initial date of administration of the investigational product to the date when objective progressive disease PD is verified by the investigator or the date of death whichever occurs first
3 Pharmacokinetic endpoint Blood is collected on Day 1 and Day 21 of Cycle 1 from available participants among the participants of this clinical trial for pharmacokinetic evaluation In all clinical trials blood collection for pharmacokinetic evaluation is performed prior to the administration of the investigational product - 60 minutes and after the administration of the investigational product at 016 h 3 minutes 05 h 3 minutes 1 h 5 minutes 2 h 10 minutes 4 h 10 minutes 8 h 30 minutes and 24 h 30 minutes
Cycle 1 Day 1 AUClast AUCinf Cmax Tmax t12 CLF VdF Cycle 1 Day 21 AUClastss AUCtauss AUCinfss Cmaxss Tmaxss t12ss CLssF VdssF
4 Exploratory endpoints Compare changes of the biomarker from the value before TB511 treatment screening visit to the post-treatment value Day 21
Category Analysis method Examination items Tumor tissue ELISA CD18 CD163 TGF-ß1 IL-10 VEGF IFN-γ Granzyme B Blood ELISA TGF-ß1 VEGF TNF-α IFN-γ IL-2 Flow cytometer Tcell NK cell CD45 CD3CD45CD3 T cells CD4 IFN-γ Activation CD25 CD8 Granzyme BActivation CD56 CD45CD3-CD19-CD56 NK CD19CD45CD3-CD19 B cell
Anti-drug antibody ADA to TB511 is measured on Day 1 of Cycle 1 and every 2 cycles both before and after the administration of TB511 end of study and safety follow-up if needed to compare changes
Phase I Clinical Trial 3 to 6 participants per dose group Phase IIa Clinical Trial Approximately 20 participants per cohort Cohort 1 Approximately 20 participants Cohort 2 Approximately 20 participants
2 Study Duration
Total clinical trial duration Approximately 36 months from the IRB approval date however this may change depending on the time taken by participants to enroll Duration of participation of individual participants Screening period Up to 4 weeks 28 days Treatment period 1 cycle consists of 3 weeks 21 days and administration is continued until there are reasons to suspend administration
Safety follow-up period 6 weeks after the end of treatment EOT
3 Investigational Product
1 Study drug Product name or code TB511 Injection 8 mg Formulation and appearance White or off-white color of lyophilized powder Main ingredient TB511 Storage method Store in a hermetic container in a freezer -20 protect from light
2 Concomitant drug Product name or code Keytruda Formulation and appearance An injection comprised of clear to slightly opalescent colorless to slightly yellow liquid contained in a colorless and transparent vial
Main ingredient Pembrolizumab Storage method Store in a hermetic container refrigerated at 2 to 8 protect from light do not freeze
4 Dosage and method of administration
Phase I Clinical Trial
1 TB511 Initial dose 4 mg Dose escalation 4 mg 8 mg 16 mg 24 mg Administration method 1 cycle consists of 3 weeks 21 days Administer subcutaneously into the abdomen once every 7 days for 3 weeks 21 days Avoid repeat injection at the same site during subcutaneous injection and administer injections while changing the location within the same area abdomen In addition do not inject into the skin that is irritated or abnormal scar rash redness tenderness etc
Administration plan Administration is continued until intolerable toxicity verification of progressive disease PD under RECIST v11 or other reasons for discontinuing administration occur
Phase 2a Clinical Trial
1 TB511 Dose Recommended dose for Phase IIa determined in Phase I Administration method 1 cycle consists of 3 weeks 21 days Administer subcutaneously into the abdomen once every 7 days for 3 weeks 21 days Avoid repeat injection at the same site during subcutaneous injection and administer injections while changing the location within the same area abdomen In addition do not inject into the skin that is irritated or abnormal scar rash redness tenderness etc
Administration plan Administration is continued until intolerable toxicity verification of progressive disease PD under RECIST v11 or other reasons for discontinuing administration occur
2 Pembrolizumab Dose 200 mg or dose adjusted in accordance with the label Administration method Pembrolizumab is administered by continuous intravenous infusion for 30 minutes once every 3 weeks if pembrolizumab is administered with TB511 TB511 is administered at least 30 minutes after Pembrolizumab injection
Administration plan Administration is continued until intolerable toxicity verification of progressive disease PD under RECIST v11 or other reasons for discontinuing administration occur
5 Study Method
This clinical trial comprises a Phase I dose-escalation study to determine the maximum tolerated dose MTD of TB511 in participants with an advanced solid tumor who are either refractory or intolerant to standard of care and to determine the recommended Phase 2a dose RP2D and a Phase IIa study to verify the anti-tumor effect of TB511 monotherapy in dose determined in Phase I Cohort 1 and in combination with Pembrolizumab Cohort 2 in participants with an advanced solid tumor with no standard of care who have refractory or have relapsed after treatment with anti-PD-1 or PD-L1 ICIs
Participants who have voluntarily signed the written informed consent form undergo a screening test to verify eligibility of participation in this clinical trial during the screening period Participants who have been determined to be eligible in accordance with the inclusion and exclusion criteria are enrolled into this clinical trial and receive the determined dose of the investigational product 1 cycle of administration of the investigational product is 3 weeks 21 days and enrolled participants continue to receive the investigational product until intolerable toxicity verification of progressive disease PD under RECIST v11 or other reasons for discontinuing administration occur RECIST CTMRI is performed on Day 1 of cycle 1 and every 2 cycles thereafter Pharmacokinetic evaluation is performed on Day 1 and Day 21 of Cycle 1 and exploratory evaluation is conducted at the screening and Day 21 of Cycle 1
Phase I Clinical Trial TB511 Monotherapy Phase I clinical trial is conducted on a 3 3 basis beginning with the lowest-dose cohort until MTD is determined Depending on the method of determining MTD 3 to 6 participants are enrolled in the order for each dose level TB511 4 mg 8 mg 16 mg 24 mg with a minimum interval of 3 days and TB511 is administered for Cycle 1 in order to determine DLT DLT assessment is conducted in Cycle 1 and whether to escalate dose is determined by the Safety Review Committee SRC after the Cycle 1 DLT assessment has been completed for the last participant RP2D of Phase IIa clinical trial is determined through MTD and overall toxicity assessment
Phase IIa Clinical Trial Phase IIa clinical trial is conducted in approximately 20 participants with an advanced solid tumor for which there is no standard of care who is subject to TB511 monotherapy cohort Cohort 1 and approximately 20 participants with advanced solid tumor who have refractory or have relapsed after treatment with anti-PD-1 or ICIs that are PD-L1 inhibitors and for whom there is no standard of care who is subject to TB511 and Pembrolizumab combination therapy cohort Cohort 2
Cohort 1 TB511 Monotherapy Cohort For Cohort 1 participants are enrolled consecutively and treated with the RP2D dose of TB511 determined in the Phase I clinical trial
Cohort 2 TB511 and Pembrolizumab Combination Cohort For Cohort 2 the first 3 participants are enrolled serially with a minimum interval of 3 days and administered in combination of the RP2D dose of TB511 and Pembrolizumab for Cycle 1 to evaluate DLT If DLT occurs the 3 3 design is applied and the SRC thereby evaluate the safety of a total of 6 participants When DLT occurs in 2 out of 3 to 6 subjects the safety of combination therapy of a TB511 dose lower than the RP2D determined in Phase I and Pembrolizumab may be evaluated by the SRC in the same manner as above If the safety of combination therapy of TB511 and Pembrolizumab is determined per the decision of the SRC the remaining participants are simultaneously enrolled and participate in the clinical trial
Phase IIa Study Scheme
1 Definition and Assessment of Dose Limiting Toxicity DLT DLT is an adverse event or abnormal laboratory level unrelated to the progress of the disease or intercurrent disease that limits dose escalation and is consistent with one or more of the following criteria DLT assessment is conducted only at Cycle 1 after completion of Cycle 1 However even during Cycle 1 DLT can be immediately evaluated if toxicity is determined to be DLT DLT assessment is conducted in accordance with NCI-CTCAE v50 based on individual assessment items on hematologicalnon-hematological toxicity and other toxicities
6 Endpoints
1 Safety Endpoints Adverse Events Vital signs Physical examination Electrocardiogram Laboratory test
2 Primary endpoint Response Evaluation Criteria in Solid Tumors - RECIST Phase I Clinical Trial Solid tumor response is evaluated in accordance with RECIST v11 Objective response rate ORR Fraction of participants whose best overall response is Complete Response CR or Partial Response PR Disease control rate DCR Fraction of participants whose best overall response is CR PR or Stable Disease SD Duration of response DoR From the point of time when response occurs to CR or PR PD or death due to any reason
Phase IIa Clinical Trial Solid tumor response is evaluated in accordance with RECIST v11 and immune RECIST iRECIST
Objective response rate ORR Fraction of participants whose best overall response is CR or PR Disease control rate DCR Fraction of participants whose best overall response is CR PR or SD Duration of response DoR From the point of time when response occurs to CR or PR PD or death due to any reason
Progression-free survival PFS period Period from the initial date of administration of the investigational product to the date when objective progressive disease PD is verified by the investigator or the date of death whichever occurs first
3 Pharmacokinetic endpoint Blood is collected on Day 1 and Day 21 of Cycle 1 from available participants among the participants of this clinical trial for pharmacokinetic evaluation In all clinical trials blood collection for pharmacokinetic evaluation is performed prior to the administration of the investigational product - 60 minutes and after the administration of the investigational product at 016 h 3 minutes 05 h 3 minutes 1 h 5 minutes 2 h 10 minutes 4 h 10 minutes 8 h 30 minutes and 24 h 30 minutes
Cycle 1 Day 1 AUClast AUCinf Cmax Tmax t12 CLF VdF Cycle 1 Day 21 AUClastss AUCtauss AUCinfss Cmaxss Tmaxss t12ss CLssF VdssF
4 Exploratory endpoints Compare changes of the biomarker from the value before TB511 treatment screening visit to the post-treatment value Day 21
Category Analysis method Examination items Tumor tissue ELISA CD18 CD163 TGF-ß1 IL-10 VEGF IFN-γ Granzyme B Blood ELISA TGF-ß1 VEGF TNF-α IFN-γ IL-2 Flow cytometer Tcell NK cell CD45 CD3CD45CD3 T cells CD4 IFN-γ Activation CD25 CD8 Granzyme BActivation CD56 CD45CD3-CD19-CD56 NK CD19CD45CD3-CD19 B cell
Anti-drug antibody ADA to TB511 is measured on Day 1 of Cycle 1 and every 2 cycles both before and after the administration of TB511 end of study and safety follow-up if needed to compare changes
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None