Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cancer
Conditions
Keywords
Platinum-sensitive, Ovarian cancer, Folate-receptor alpha expression, Antibody-drug conjugate, Cancer, Ovarian Neoplasma, Recurrent Platinum-Sensitive, High-Grade Ovarian, PICCOLO
Brief summary
PICCOLO (IMGN853-0419) is a Phase 2 multicenter, open label study designed to evaluate the safety and efficacy of Mirvetuximab Soravtansine in participants with platinum-sensitive ovarian, primary peritoneal or fallopian tube cancers with high folate receptor-alpha (FRα) expression.
Detailed description
Mirvetuximab Soravtansine (MIRV) is an investigational antibody drug conjugate designed to selectively kill cancer cells. The antibody (protein) part of MIRV targets tumors by delivering a cell-killing drug to the tumor cells carrying a tumor-associated protein called folate receptor alpha (FRα). It is being developed for the treatment of participants with recurrent platinum-sensitive, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression. Participants will have had at least 2 prior lines of therapy. These will include at least 2 lines of platinum-containing therapy or 1 line with a documented platinum allergy. FRα positivity will be defined by the Ventana FOLR1 (FOLR1- 2.1) CDx assay (Ventana FOLR1 Assay).
Interventions
DRUGMirvetuximab soravtansine
Administered by intravenous (IV) infusion on Day 1 of every 3-week cycle
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants ≥ 18 years of age 2. Participants must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 3. Participants must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer 4. Participants must have platinum-sensitive disease defined as radiographic progression greater than 6 months from last dose of most recent platinum therapy Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression 5. Participants must have progressed radiographically on or after their most recent line of anticancer therapy 6. Participants must have at least 1 lesion that meets the definition of measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (radiologically measured by the Investigator) 7. Participants must be willing to provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα positivity 8. Participant's tumor must be positive for FRα expression as defined by the Ventana FOLR1 Assay 9. Prior anticancer therapy 1. Participants must have received at least 2 prior systemic lines of platinum therapy and be considered by the Investigator as appropriate for single-agent non-platinum therapy (documentation required - for example, high risk of hypersensitivity reaction; risk of further cumulative toxicity with additional platinum, including but not limited to myelosuppression, neuropathy, renal insufficiency or other) i. Note: Participants who have had a documented platinum allergy may have had only 1 prior line of platinum 2. Participants may have received up to but no more than 1 prior independent non-platinum cytotoxic therapy 3. Participants must have had testing for breast cancer susceptibility gene (BRCA) mutation (tumor or germline) and, if positive, must have received a prior poly (ADP-ribose) polymerase (PARP) inhibitor as either treatment or maintenance therapy 4. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy 5. Maintenance therapy (for example, bevacizumab, PARP inhibitors) will be considered part of the preceding line of therapy (that is, not counted independently) 6. Therapy changed due to toxicity in the absence of progression will be considered part of the same line (that is, not counted independently) 10. Participants must have completed prior therapy within the specified times below: 1. Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to first dose of MIRV 2. Focal radiation completed at least 2 weeks prior to first dose of MIRV 11. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia) 12. Participants must have completed any major surgery at least 4 weeks prior to first dose of MIRV and have recovered or stabilized from the side effects of prior surgery prior to first dose of MIRV 13. Participants must have adequate hematologic, liver and kidney functions defined as: 1. Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/liter (L) (1500/microliter \[μL\]) without granulocyte colony-stimulating factor (G-CSF) in the prior 10 days or long-acting white blood cell (WBC) growth factors in the prior 20 days 2. Platelet count ≥ 100 x 10\^9/L (100,000/μL) without platelet transfusion in the prior 10 days 3. Hemoglobin ≥ 9.0 grams (g)/deciliter (dL) without packed red blood cell (PRBC) transfusion in the prior 21 days 4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) 5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN 6. Serum bilirubin ≤ 1.5 x ULN (participants with documented diagnosis of Gilbert syndrome are eligible if total bilirubin \< 3.0 x ULN) 7. Serum albumin ≥ 2 g/dL 14. Participants must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements 15. Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) while on MIRV and for at least 3 months after the last dose 16. WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV
Exclusion criteria
1. Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/ borderline ovarian tumor 2. Participants with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow 3. Participants with \> Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) 4. Participants with active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and/or monocular vision 5. Participants with serious concurrent illness or clinically relevant active infection, including, but not limited to the following: 1. Active hepatitis B or C infection (whether or not on active antiviral therapy) 2. Human immunodeficiency virus (HIV) infection 3. Active cytomegalovirus infection 4. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to the first dose of MIRV Note: Testing at screening is not required for the above infections unless clinically indicated. 6. Participants with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome) 7. Participants with clinically significant cardiac disease including, but not limited to, any of the following: 1. Myocardial infarction ≤ 6 months prior to first dose 2. Unstable angina pectoris 3. Uncontrolled congestive heart failure (New York Heart Association \> class II) 4. Uncontrolled ≥ Grade 3 hypertension (per CTCAE) 5. Uncontrolled cardiac arrhythmias 8. Participants with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment 9. Participants with a history of cirrhotic liver disease (Child-Pugh Class B or C) 10. Participants with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis 11. Participants requiring use of folate-containing supplements (for example, folate deficiency) 12. Participants with prior hypersensitivity to monoclonal antibodies (mAb) 13. Women who are pregnant or breastfeeding 14. Participants who received prior treatment with MIRV or other FRα-targeting agents 15. Participants with untreated or symptomatic central nervous system (CNS) metastases 16. Participants with a history of other malignancy within 3 years prior to enrollment Note: Participants with tumors with a negligible risk for metastasis or death (for example, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible. 17. Prior known hypersensitivity reactions to study drugs and/or any of their excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1]) | Up to 3 years | ORR was defined as percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). PR: At least 30% decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) Assessed by the Investigator Using RECIST v1.1 | Up to 3 years | DOR was defined as the time from the date of the first response (CR or PR), until the date of progressive disease (PD) or death from any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. DOR was estimated using the Kaplan-Meier method. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to 3 years | An adverse event (AE) was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and does not necessarily had a causal relationship to study drug. TEAEs were defined as AEs with an onset date on or after the first dose of Study drug, and within 30 days of the last dose of study drug or prior to the start of a new anticancer treatment, whichever occurred first. A summary of all Serious Adverse Events (SAEs) and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Percentage of Participants With CA-125 Confirmed Clinical Response Per Gynecologic Cancer Intergroup (GCIG) Criteria | Up to 3 years | The GCIG CA-125 response was defined as at least 50% reduction in CA-125 levels from baseline. The response must have been confirmed and maintained for at least 28 days. |
| Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 | Up to 3 years | PFS was defined as the time from initiation of study drug until the date of PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. |
| Overall Survival Assessed by the Investigator Using RECIST v1.1 | Up to 3 years | Overall survival was defined as the time from the date of first dose until the date of death from any cause, estimated using the Kaplan-Meier method. |
Countries
Australia, Belgium, France, Ireland, Italy, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mirvetuximab Soravtansine Participants received single-agent mirvetuximab soravtansine at 6 mg/kg AIBW administered through IV infusion on Day 1 of every 3-week cycle. | 79 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 37 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Sponsor decision | 39 |
Baseline characteristics
| Characteristic | Mirvetuximab Soravtansine |
|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 10.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 65 Participants |
| Sex: Female, Male Female | 79 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 37 / 79 |
| other Total, other adverse events | 77 / 79 |
| serious Total, serious adverse events | 17 / 79 |
Outcome results
Primary
Objective Response Rate (ORR) Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1])
ORR was defined as percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). PR: At least 30% decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD.
Time frame: Up to 3 years
Population: Efficacy Evaluable Population Per Investigator included all participants who received at least 1 dose of mirvetuximab soravtansine and had measurable disease at baseline per Investigator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mirvetuximab Soravtansine | Objective Response Rate (ORR) Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1]) | 51.9 percentage of participants |
Secondary
Duration of Response (DOR) Assessed by the Investigator Using RECIST v1.1
DOR was defined as the time from the date of the first response (CR or PR), until the date of progressive disease (PD) or death from any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. DOR was estimated using the Kaplan-Meier method.
Time frame: Up to 3 years
Population: Efficacy Evaluable Population Per Investigator included all participants who received at least 1 dose of mirvetuximab soravtansine and had measurable disease at baseline per Investigator. 'Overall number of participants analyzed' = participants with objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine | Duration of Response (DOR) Assessed by the Investigator Using RECIST v1.1 | 8.25 months |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and does not necessarily had a causal relationship to study drug. TEAEs were defined as AEs with an onset date on or after the first dose of Study drug, and within 30 days of the last dose of study drug or prior to the start of a new anticancer treatment, whichever occurred first. A summary of all Serious Adverse Events (SAEs) and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Up to 3 years
Population: Safety Population included all participants who received at least 1 dose of mirvetuximab soravtansine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mirvetuximab Soravtansine | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 78 Participants |
Secondary
Overall Survival Assessed by the Investigator Using RECIST v1.1
Overall survival was defined as the time from the date of first dose until the date of death from any cause, estimated using the Kaplan-Meier method.
Time frame: Up to 3 years
Population: Efficacy Evaluable Population Per Investigator included all participants who received at least 1 dose of mirvetuximab soravtansine and had measurable disease at baseline per Investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine | Overall Survival Assessed by the Investigator Using RECIST v1.1 | 27.17 months |
Secondary
Percentage of Participants With CA-125 Confirmed Clinical Response Per Gynecologic Cancer Intergroup (GCIG) Criteria
The GCIG CA-125 response was defined as at least 50% reduction in CA-125 levels from baseline. The response must have been confirmed and maintained for at least 28 days.
Time frame: Up to 3 years
Population: CA-125 Response-Evaluable Population included all participants who received at least 1 dose of mirvetuximab soravtansine, whose pretreatment sample was ≥ 2.0 times the upper limit of normal (ULN), within 2 weeks prior to first dose of mirvetuximab soravtansine, and who had at least 1 post-baseline CA-125 evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mirvetuximab Soravtansine | Percentage of Participants With CA-125 Confirmed Clinical Response Per Gynecologic Cancer Intergroup (GCIG) Criteria | 74.5 percentage of participants |
Secondary
Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1
PFS was defined as the time from initiation of study drug until the date of PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Time frame: Up to 3 years
Population: Efficacy Evaluable Population Per Investigator included all participants who received at least 1 dose of mirvetuximab soravtansine and had measurable disease at baseline per Investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine | Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 | 6.93 months |