Metastatic Solid Tumor
Conditions
Brief summary
The goal of this clinical study is to learn more about the study drug, sacituzumab govitecan-hziy, in participants with metastatic (cancer that has spread) solid tumors.
Interventions
DRUGSacituzumab Govitecan-hziy
Administered intravenously
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Individuals with the following histologically documented metastatic (M1, Stage IV) or locally advanced solid tumors * NSCLC \[adenocarcinoma or squamous cell carcinoma (SCC)\] that has progressed after prior platinum-based chemotherapy and programmed death-(ligand) 1 (PD-(L)1) directed therapy * HNSCC that has progressed after prior platinum-based chemotherapy and anti-PD-(L)1 directed therapy No more than 3 prior lines of systemic treatment is allowed * Endometrial carcinoma that has progressed after prior platinum-based chemotherapy and anti-PD-(L)1 directed therapy No more than 3 prior lines of systemic treatment is allowed. * Extensive stage SCLC that has progressed after prior platinum-based chemotherapy and PD-(L)1 directed therapy. No more than one prior line of systemic treatment is allowed (re-challenge with the same initial regimen is not allowed) * Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1 * Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation * Adequate hepatic and renal function \[Creatinine Clearance (CrCl) ≥30mL/min\] * Individual must have at least a 3-month life expectancy * Have measurable disease by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria Key
Exclusion criteria
* Have had a prior anti-cancer biologic agent within 4 weeks prior to study Day 1 or have had prior chemotherapy, targeted small molecule therapy, radiation therapy within 2 weeks prior to Study Day 1 * Have not recovered (i.e., ≤ Grade 1) from adverse events due to a previously administered agent * Have previously received topoisomerase I inhibitors * Have an active second malignancy * Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Individuals with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases and are taking ≤20 mg/day of prednisone or its equivalent. All individuals with carcinomatous meningitis are excluded regardless of clinical stability * Additional cohort specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator's Assessment | Cohort 1: Up to 5.3 years; Cohort 2: Up to 3.4 years; Cohort 3: Up to 3.3 years; Cohort 4: Up to 2.5 years | ORR was defined as the percentage of participants who had the best overall response of either complete response (CR) or partial response (PR). Responses are based on the investigator-assessed tumor response using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria for each histologic cohort. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; PR: \>30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. The ORR rate was calculated with a two-sided exact 95% CI using the Clopper-Pearson method. Percentages are rounded off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR According to RECIST 1.1 by Blinded Independent Central Review (BICR) Assessment | Cohort 1: Up to 5.3 years; Cohort 2: Up to 3.4 years; Cohort 3: Up to 3.3 years; Cohort 4: Up to 2.5 years | ORR was defined as the percentage of participants who had the best overall response of either CR or PR. Responses are based on BICR assessment using RECIST 1.1 criteria for each histologic cohort. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; PR: \>30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. The ORR rate was calculated with a two-sided exact 95% CI using the Clopper-Pearson method. |
| Duration of Response (DOR) According to RECIST 1.1 by BICR Assessment | Cohort 1: Up to 5.3 years; Cohort 2: Up to 3.4 years; Cohort 3: Up to 3.3 years; Cohort 4: Up to 2.5 years | DOR was the date of the first evaluation showing documented response, either PR or CR, to date of the first progression of disease (PD) or death from any cause,whichever comes first. Response are according to RECIST 1.1 by BICR for each histological cohort. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal;PR: \>30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Disease progression was defined as an increase of \>20% in the sum of diameters of target lesions, taking as reference the smallest sum on study(this includes the baseline sum if that is the smallest on study). In addition, the sum must also demonstrate an absolute increase of more than 5 mm or the appearance of ≥ 1 new non-target lesions and/or unequivocal progression of existing non-target lesions. DOR was estimated using Kaplan-Meier estimate. The 95% CI was computed by Brookmeyer-Crowley method. |
| Clinical Benefit Rate (CBR) According to RECIST 1.1 by BICR Assessment | Cohort 1: Up to 5.3 years; Cohort 2: Up to 3.4 years; Cohort 3: Up to 3.3 years; Cohort 4: Up to 2.5 years | CBR was percentage of participants with best overall response of CR, PR,or durable stable disease (SD) (SD ≥ 6 months after first dose). Responses are according to RECIST 1.1 by BICR.CR: Disappearance of all target and non-target lesions;\& normalization of tumor marker levels initially above upper limits of normal;PR:\>30% decrease in sum of LD of target lesions, taking as reference the baseline sum LD. SD:Neither sufficient shrinkage for PR nor sufficient increase for PD, taking reference of smallest sum LD since treatment started or ≥ 1 non-target lesions with maintenance of tumor marker level above normal limits.PD: Increase of \>20% in sum of diameters of target lesions, taking reference of smallest sum(this includes baseline sum if smallest on study), the sum must also demonstrate an absolute increase of more than 5 mm or of ≥ 1 new non-target lesions and/or unequivocal progression of existing non-target lesions. Two-sided CI was based on Clopper-Pearson method. |
| Progression-free Survival (PFS) According to RECIST 1.1 by BICR Assessment | Cohort 1: Up to 5.3 years; Cohort 2: Up to 3.4 years; Cohort 3: Up to 3.3 years; Cohort 4: Up to 2.5 years | PFS was defined as the time from the first dose until objective tumor progression or death from any cause, whichever comes first. Responses are according to RECIST 1.1 by BICR. Disease progression was defined as an increase of \>20% in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition, the sum must also demonstrate an absolute increase of more than 5 mm or the appearance ≥ 1 new non-target lesions and/or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier estimate. The 95% CI for median was computed by Brookmeyer-Crowley method. |
| DOR According to RECIST 1.1 by Investigator's Assessment | Cohort 1: Up to 5.3 years; Cohort 2: Up to 3.4 years; Cohort 3: Up to 3.3 years; Cohort 4: Up to 2.5 years | DOR was the date of the first evaluation showing documented response, either PR or CR, to date of the first PD or death from any cause, whichever comes first. Responses are based on investigator-assessed tumor response by RECIST 1.1 criteria for each histological cohort.CR:Disappearance of all target and non-target lesions;and normalization of tumor marker levels initially above upper limits of normal;PR:\>30% decrease in the sum of the LD of target lesions,taking as reference the baseline sum LD. Disease progression was defined as increase of \>20% in sum of diameters of target lesions, taking as reference the smallest sum on study(this includes the baseline sum if that is the smallest on study).In addition, the sum must also demonstrate an absolute increase of more than 5 mm or the appearance of ≥ 1 new non-target lesions and/or unequivocal progression of existing non-target lesions. DOR was estimated using Kaplan-Meier estimate. The 95% CI was computed by Brookmeyer-Crowley method. |
| CBR According to RECIST 1.1 by Investigator's Assessment | Cohort 1: Up to 5.3 years; Cohort 2: Up to 3.4 years; Cohort 3: Up to 3.3 years; Cohort 4: Up to 2.5 years | CBR was the percentage of participants with the best overall response of CR, PR,or durable SD (SD ≥ 6 months after first dose) by investigator-assessed tumor response using RECIST 1.1 criteria.CR:Disappearance of all target and non-target lesions;\& normalization of tumor marker levels initially above upper limits of normal;PR:\>30% decrease in sum of LD of target lesions,taking as reference the baseline sum LD. SD:Neither sufficient shrinkage for PR nor sufficient increase for PD,taking reference of smallest sum LD since treatment started or ≥ 1 non-target lesions with maintenance of tumor marker level above normal limits.PD: Increase of \>20% in sum of diameters of target lesions,taking reference of smallest sum(this includes baseline sum if smallest on study),the sum must also demonstrate an absolute increase of more than 5 mm or of ≥ 1 new non-target lesions and/or unequivocal progression of existing non-target lesions.Two-sided CI was based on Clopper-Pearson method. |
| PFS According to RECIST 1.1 by Investigator's Assessment | Cohort 1: Up to 5.3 years; Cohort 2: Up to 3.4 years; Cohort 3: Up to 3.3 years; Cohort 4: Up to 2.5 years | PFS was defined as the time from the first dose until objective tumor progression or death from any cause, whichever comes first. Responses are based on the investigator-assessed tumor response using RECIST 1.1 criteria. Disease progression was defined as an increase of \>20% in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition, the sum must also demonstrate an absolute increase of more than 5 mm or the appearance ≥ 1 new non-target lesions and/or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier estimate. The 95% CI for median was computed by Brookmeyer-Crowley method. |
| Overall Survival (OS) | Cohort 1: Up to 5.3 years; Cohort 2: Up to 3.4 years; Cohort 3: Up to 3.3 years; Cohort 4: Up to 2.5 years | OS was defined as the interval from the first dose date of drug to death from any cause. OS was estimated using Kaplan-Meier estimate. The 95% CI for median was computed by Brookmeyer-Crowley method. |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | Up to 7.2 years | A TEAE was defined as any AE with an onset date on or after the study drug start date and no later than 30 days after last dose of study drug or the day before initiation of subsequent therapy, whichever comes first. |
| Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities | Up to 7.2 years | A treatment-emergent laboratory abnormality was defined as any value that increased at least 1 toxicity grade from baseline during the treatment-emergent period. |
| Pharmacokinetic (PK) Parameter: Cmax of Total SN-38 | Cohort 1: Post dose: Day 1 of Cycles 1,2,3,7,11,17,23,29,35,41,47; Cohort 2: Post dose: Day 1 of Cycles 1,2,3,7,11,17; Cohort 3: Post dose: Day 1 of Cycles 1,2,3,7,11,17,23,29,35,41,47,53; Cohort 4: Post dose: Day 1 of Cycles 1,2,3,7,11,17,23,29 | Cmax was defined as the maximum observed concentration of total SN-38 (the active metabolite of sacituzumab Govitecan-hziy). Cycle length=21 days. |
| PK Parameter: Cmax of Free SN-38 | Cohort 1: Post dose: Day 1 of Cycles 1,2,3,7,11,17,23,29,35,41,47; Cohort 2: Post dose: Day 1 of Cycles 1,2,3,7,11,17; Cohort 3: Post dose: Day 1 of Cycles 1,2,3,7,11,17,23,29,35,41,47,53; Cohort 4: Post dose: Day 1 of Cycles 1,2,3,7,11,17,23,29 | Cmax was defined as the maximum observed concentration of free SN-38 (the active metabolite of sacituzumab Govitecan-hziy). Cycle length=21 days. |
| PK Parameter: Cmax of Total Antibody | Cohort 1: Post dose: Day 1 of Cycles 1,2,3,7,11,17,23,29,35,41,47; Cohort 2: Post dose: Day 1 of Cycles 1,2,3,7,11,17; Cohort 3: Post dose: Day 1 of Cycles 1,2,3,7,11,17,23,29,35,41,47,53; Cohort 4: Post dose: Day 1 of Cycles 1,2,3,7,11,17,23,29 | Cmax was defined as the maximum observed concentration of total antibody of SG \[hRS7 immunoglobulin (IgG) and hRS7-SN-38\]. Cycle length=21 days. |
| PK Parameter: Ctrough of Total SN-38 | C1:PD,D1:Cycles1,2,3,7,11,17,23,29,35,41,47,EOT(Upto 38.7months)&SFU;C2:PD,D1:Cycles1,2,3,7,11,17,EOT(Upto 12.3months)&SFU;C3:PD,D1:Cycles1,2,3,7,11,17,23,29,35,41,47,53,EOT(Upto 40.0months)&SFU;C4:PD,D1:Cycles1,2,3,7,11,17,23,29,EOT(Upto 29.3months)&SFU | Ctrough was defined as concentration at the end of the dosing interval of total SN-38 (the active metabolite of sacituzumab Govitecan-hziy). Cycle length=21 days; C=Cohort; D=Day; EOT=End of Treatment; PD=predose; SFU=Safety Follow-up (up to 30 days after EOT date) |
| PK Parameter: Ctrough of Free SN-38 | C1:PD,D1:Cycles1,2,3,7,11,17,23,29,35,41,47,EOT(Upto 38.7months)&SFU;C2:PD,D1:Cycles1,2,3,7,11,17,EOT(Upto 12.3months)&SFU;C3:PD,D1:Cycles1,2,3,7,11,17,23,29,35,41,47,53,EOT(Upto 40.0months)&SFU;C4:PD,D1:Cycles1,2,3,7,11,17,23,29,EOT(Upto 29.3months)&SFU | Ctrough was defined as concentration at the end of the dosing interval of free SN-38 (the active metabolite of sacituzumab Govitecan-hziy). Cycle length=21 days; C=Cohort; D=Day; EOT=End of Treatment; PD=predose; SFU=Safety Follow-up (up to 30 days after EOT date) |
| PK Parameter: Ctrough of Total Antibody | C1:PD,D1:Cycles1,2,3,7,11,17,23,29,35,41,47,EOT(Upto 38.7months)&SFU;C2:PD,D1:Cycles1,2,3,7,11,17,EOT(Upto 12.3months)&SFU;C3:PD,D1:Cycles1,2,3,7,11,17,23,29,35,41,47,53,EOT(Upto 40.0months)&SFU;C4:PD,D1:Cycles1,2,3,7,11,17,23,29,EOT(Upto 29.3months)&SFU | Ctrough was defined as concentration at the end of the dosing interval of total antibody of SG \[hRS7 immunoglobulin (IgG) and hRS7-SN-38\]. Cycle length=21 days; C=Cohort; D=Day; EOT=End of Treatment; PD=predose; SFU=Safety Follow-up (up to 30 days after EOT date) |
| Percentage of Participants With Positive Anti-SG Antibodies | C1:PD,D1:Cycles1,2,3,7,11,17,23,29,35,41,47,EOT(Upto 38.7months)&SFU;C2:PD,D1:Cycles1,2,3,7,11,17,EOT(Upto 12.3months)&SFU;C3:PD,D1:Cycles1,2,3,7,11,17,23,29,35,41,47,53,EOT(Upto 40.0months)&SFU;C4:PD,D1:Cycles1,2,3,7,11,17,23,29,EOT(Upto 29.3months)&SFU | Cycle length=21 days; C=Cohort; D=Day; EOT=End of Treatment; PD=predose; SFU=Safety Follow-up (up to 30 days after EOT date) |
Countries
Australia, Belgium, Canada, France, Hong Kong, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States, France, Australia, Hong Kong, Spain, Taiwan, Canada, and Belgium.
Pre-assignment details
396 participants were screened. Data submitted represent primary analysis performed on data collected by the Primary Completion Date. Complete data will be submitted within 1 year of the study completion date.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 113 Participants |
| Age, Categorical Between 18 and 65 years | 110 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 200 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 5 Participants |
| Race/Ethnicity, Customized Race Black or African American | 3 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Race Other or More Than One Race | 2 Participants |
| Race/Ethnicity, Customized Race Unknow or Not Reported | 12 Participants |
| Race/Ethnicity, Customized Race White | 163 Participants |
| Region of Enrollment Australia | 0 Participants |
| Region of Enrollment Belgium | 2 Participants |
| Region of Enrollment Canada | 3 Participants |
| Region of Enrollment France | 12 Participants |
| Region of Enrollment Hong Kong | 0 Participants |
| Region of Enrollment Spain | 9 Participants |
| Region of Enrollment Taiwan | 2 Participants |
| Region of Enrollment United States | 173 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 26 / 31 | 27 / 34 | 28 / 31 | 35 / 43 | 30 / 41 | 32 / 43 |
| other Total, other adverse events | 30 / 31 | 34 / 34 | 30 / 31 | 43 / 43 | 40 / 41 | 43 / 43 |
| serious Total, serious adverse events | 15 / 31 | 11 / 34 | 13 / 31 | 13 / 43 | 19 / 41 | 22 / 43 |
Outcome results
None listed