Ovarian Cancer, Solid Tumors
Conditions
Brief summary
The main aim of this study are to check for side effects from TAK-853, check how much TAK-853 participants can receive without getting side effects from it, check how well TAK-853 controls symptoms, and to check how much TAK-853 stays in their blood over time. The study will be conducted in two phases including Phase 1 Part and Phase 2 Part. In Phase 1 Part, the participants will stay in the hospital for 3 days at least after their 1st injection for some tests and to check for any side effects from their treatment. In Phase 2 Part, participants will visit their study hospital for multiple times. In both phases, the participants will receive TAK-853 on the first days of each 3-week cycle. The participant will be in the study for about 9 months in Phase 1 Part and for about 24 months in Phase 2 Part. The study doctors will check for side effects from the study treatments.
Interventions
DRUGTAK-853
TAK-853 intravenous injection
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase 1 part: 1. Diagnosis, allowable prior therapy, and disease measurability requirements: 1. All participants must have a pathologically documented, following advanced solid tumor known to express folate receptor alpha (FR alpha), that is resistant or refractory to standard treatment, for which no standard treatment is available, or the participant refuses standard therapy. * Ovarian cancer * Endometrial cancer * Non-small cell lung cancer (NSCLC) * Triple-negative breast cancer (TNBC) * Cholangiocarcinoma * Colorectal cancer (CRC) * Gastro-esophageal adenocarcinoma Note: Participants with a solid tumor type other than the above will be eligible as long as there is prior documentation of tumor FR alpha expression. 2. All participants without prior documentation of tumor FR alpha expression by immunohistochemistry (IHC) 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 IHC confirmation of FR alpha positivity of \>=1% of viable tumor cells with membrane staining at \>=1+ intensity for entry into Phase 1 part 3. There is no upper limit on the number of prior cytotoxic or targeted therapies the participant may have received. Participants may have received prior treatment with investigational compounds targeting folate receptor excluding MIRV. 4. Participants must have measurable or non-measurable disease (such as large abdominal masses that cannot be accurately measured) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. 2. Participant must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 3. Time from Prior Therapy: * Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is shorter (6 weeks for prior nitrosoureas or mitomycin C) * FR alpha-targeted therapy: five half-lives or four weeks, whichever is longer * Radiotherapy: wide-field radiotherapy (e.g. affecting at least 30% of the bone marrow) completed at least four weeks, or focal radiation completed at least two weeks, prior to starting study drug 4. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities 5. Major surgery must be completed four weeks prior to first dose of TAK-853. Participants must have recovered or stabilized from the side effects prior to study treatment. 6. Participants must have adequate hematologic, liver and kidney function as defined by the following parameters: 1. Absolute neutrophil count (ANC) \>= 1.5\*10\^9/L (1,500/microliter) 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 \>= 100.0\*10\^9/L (100,000/microliter; without platelet transfusion in the prior 10 days) 3. Hemoglobin \>= 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days 4. Serum creatinine =\< 1.5\* upper limit of normal (ULN) or estimated creatinine clearance of \>= 30 mL/minute (as calculated using the Cockcroft Gault equation), 5. Aspartate aminotransferase (AST) =\< 2.5\* ULN; alanine aminotransferase (ALT) =\< 2.5\* ULN (AST, ALT \< 5\* ULN if liver metastases), and 6. Total bilirubin =\< 1.5\* ULN (participants with documented diagnosis of Gilbert syndrome are eligible if total bilirubin \< 3.0\* ULN) 7. Participants with central nervous system (CNS) disease involvement are eligible if they have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study Day 1 and they meet all of the following criteria: <!-- --> 1. Residual neurological symptoms =\< Grade 1 2. No dexamethasone requirement, and 3. Follow-up MRI shows no progression of treated lesions and no new lesions appearing. Phase 2 part: 1. Participants must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer 2. Participants must have platinum-resistant disease: 1. Participants who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response (complete response \[CR\] or partial response \[PR\]) and then progressed between \> 3 months and =\< 6 months after the last dose date of platinum 2. Participants who have received 2 or 3 lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum 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 Note: Participants who are primary platinum-refractory during front-line treatment are excluded (see
Exclusion criteria
) 3. Participants must have progressed radiographically on or after their most recent line of therapy 4. 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 IHC confirmation of FR alpha expression (reported as "positive") as defined by the Ventana FOLR1 Assay. Tumors must be confirmed FR alpha-high as defined by FR alpha positivity of \>=75% of viable tumor cells with membrane staining at \>=2+ intensity for entry into the Phase 2. 5. Participants must have at least one lesion that meets the definition of measurable disease by RECIST v1.1 criteria (radiologically measured by the Investigator). 6. Participants must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment: a. Neoadjuvant +- adjuvant considered one line of therapy b. Maintenance therapy (e.g., bevacizumab, poly-ADP ribose polymerase \[PARP\] inhibitors) will be considered as part of the preceding line of therapy (i.e., not counted independently) c. Therapy changed due to toxicity in the absence of progression will be considered as part of the same line (i.e., not counted independently) d. Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance 7. Participant must have an ECOG PS of 0 or 1 8. Time from prior therapy: 1. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter) 2. Focal radiation completed at least 2 weeks prior to first dose of study drug 9. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities 10. Major surgery must be completed at least 4 weeks prior to first dose and the participant must have recovered or stabilized from the side effects of prior surgery 11. Participants must have adequate hematologic, liver, and kidney functions defined as: 1. ANC \>= 1.5\* 10\^9/L (1,500/microliter) without G-CSF in the prior 10 days or long-acting WBC growth factors in the prior 20 days 2. Platelet count \>= 100\* 10\^9/L (100,000/microliter) without platelet transfusion in the prior 10 days 3. Hemoglobin \>= 9.0 g/dL without PRBC transfusion in the prior 21 days 4. Serum creatinine =\< 1.5\* ULN or estimated creatinine clearance of \>= 30 mL/minute (as calculated using the Cockcroft Gault equation). 5. AST and ALT =\< 3.0\* ULN 6. Total bilirubin =\< 1.5\* ULN (participants with documented diagnosis of Gilbert syndrome are eligible if total bilirubin \< 3.0\* ULN) 7. Serum albumin \>= 2 g/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) in Cycle 1 | Up to Cycle 1 (up to 21 days) | DLT was evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0 and defined as any of following events: 1. If re-treatment was not initiated within 14 days due to adverse event (AE) related to protocol treatment; 2. Grade 4 neutropenia for more than 7 days; 3. Grade 3 or 4 neutropenia with single temperature reading \>= 38.3-degree Celsius (°C) or sustained temperature reading of greater than (\>) 38°C for \>1 hour; 4. Platelet counts decreased of Grade 3 requiring platelet transfusion or blood platelet decreased of Grade 4; 5. Grade 3 or higher non-hematologic toxicity that was considered clinically significant, except following cases, AEs related to underlying disease, Alopecia, Grade 3 fatigue, Lymphopenia unless accompanied by clinically significant infection, isolated and asymptomatic Grade 3 abnormalities in biochemistry laboratory values that last for less than and equal to (\<=) 7 days including electrolyte abnormalities. |
| Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From start of study drug up to 30 days after last dose (up to 3.7 months) | An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. |
| Phase 1: Number of Participants With Grade 3 or Higher TEAEs by Severity | From start of study drug up to 30 days after last dose (up to 3.7 months) | The severity grade was evaluated as per the NCI CTCAE Version 5.0, where Grade 1 scales as Mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 scales as Moderate (minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living \[ADL\]); Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL), Grade 4 was life-threatening consequences; urgent intervention indicated, and Grade 5 was death related to AE. TEAEs were 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 anti-cancer treatment, whichever occurs first. |
| Phase 1: Number of Participants With Serious TEAEs | From start of study drug up to 30 days after last dose (up to 3.7 months) | A serious TEAE is any untoward medical occurrence or effect that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect, and was an important medical event. |
| Phase 1: Number of Participants With TEAEs Leading to Drug Discontinuation | From start of study drug up to 30 days after last dose (up to 3.7 months) | 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 anti-cancer treatment, whichever occurred first. Number of participants with TEAEs leading to study drug discontinuation were reported. |
| Phase 1: Number of Participants With TEAEs Leading to Infusion Interruption | From start of study drug up to 30 days after last dose (up to 3.7 months) | 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 anti-cancer treatment, whichever occurred first. Number of participants with TEAEs leading to infusion interruption were reported. |
| Phase 1: Number of Participants With TEAEs Leading to Dose Delayed | From start of study drug up to 30 days after last dose (up to 3.7 months) | 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 anti-cancer treatment, whichever occurred first. Number of participants with TEAEs leading to dose delayed were reported. |
| Phase 1: Number of Participants With TEAEs Leading to Dose Reduction | From start of study drug up to 30 days after last dose (up to 3.7 months) | 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 anti-cancer treatment, whichever occurred first. Number of participants with TEAEs leading to dose reduction were reported. |
| Phase 1: Number of Participants With Adverse Event of Clinical Interest (AECIs) | From start of study drug up to 30 days after last dose (up to 3.7 months) | AECIs (serious or nonserious) were those TEAEs which were of scientific and medical concern specific to the TAK-853. AECIs for TAK-853 included: 1. Ocular TEAEs, 2. Pneumonitis TEAEs, 3. Peripheral neuropathy TEAEs and 4. Infusion related TEAEs. |
| Phase 2: Objective Response Rate (ORR) Assessed by Investigator With Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Up to 7.2 months | ORR was defined as the percentage of participants who achieved a confirmed Partial Response (PR) or confirmed Complete Response (CR) during the study using RECIST 1.1. Complete response (CR): Disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 millimeters (mm). Partial response (PR): At least a 30% decrease in the sum of diameters (SoD of target lesions, taking as reference the baseline SoD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Maximum Observed Plasma Concentration (Cmax) of TAK-853 and Total Antibody (TAb) | Cycle 1 and 3: pre-infusion, 2, 4, 6, 24, 48 hours post-infusion, and Days 4, 5, 8, and 15 post-infusion | Pharmacokinetic (PK) parameters were calculated using standard non-compartmental methods. Cmax of TAK-853 and TAb were reported at cycle 1 and cycle 3. |
| Phase 1: Cmax of N2'-Deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)- Maytansine (DM4) and S-methyl DM4 | Cycle 1 and 3: pre-infusion, 2, 4, 6, 24, 48 hours post-infusion, and Days 4, 5, 8, and 15 post-infusion | PK parameters were calculated using standard non-compartmental methods. Cmax of DM4 and S-methyl DM4 were reported at cycle 1 and cycle 3. |
| Phase 1: Area Under the Plasma Concentration-Time Curve Until Tlast (AUClast) and Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUCinf) of TAK-853 and TAb | Cycle 1 and 3: pre-infusion, 2, 4, 6, 24, 48 hours post-infusion, and Days 4, 5, 8, and 15 post-infusion | PK parameters were calculated using standard non-compartmental methods. AUClast and AUCinf of TAK-853 and TAb were reported at cycle 1 and cycle 3. |
| Phase 1: AUClast and AUCinf of DM4 and S-methyl DM4 | Cycle 1 and 3: pre-infusion, 2, 4, 6, 24, 48 hours post-infusion, and Days 4, 5, 8, and 15 post-infusion | PK parameters were calculated using standard non-compartmental methods. AUClast and AUCinf of DM4 and S-methyl DM4 were reported at cycle 1 and cycle 3. |
| Phase 1: Terminal Half-Life (t1/2) of TAK-853, TAb, DM4 and S-methyl DM4 | Cycle 1 and 3: pre-infusion, 2, 4, 6, 24, 48 hours post-infusion, and Days 4, 5, 8, and 15 post-infusion | PK parameters were calculated using standard non-compartmental methods. t1/2 of TAK-853, TAb, DM4 and S-methyl DM4 were reported at cycle 1 and cycle 3. |
| Phase 1: Total Clearance (CL) of TAK-853 and TAb | Cycle 1 and 3: pre-infusion, 2, 4, 6, 24, 48 hours post-infusion, and Days 4, 5, 8, and 15 post-infusion | PK parameters were calculated using standard non-compartmental methods. CL of TAK-853 and TAb were reported at cycle 1 and cycle 3. |
| Phase 1: Apparent Clearance (CL/F) of DM4 and S-methyl DM4 | Cycle 1 and 3: pre-infusion, 2, 4, 6, 24, 48 hours post-infusion, and Days 4, 5, 8, and 15 post-infusion | PK parameters were calculated using standard non-compartmental methods. CL/F of DM4 and S-methyl DM4 were reported at cycle 1 and cycle 3. |
| Phase 1: Volume of Distribution at Steady State (Vss) of TAK-853, TAb and Apparent Volume of Distribution During the Terminal Phase (VZ/F) of DM4 and S-methyl DM4 | Cycle 1 and 3: pre-infusion, 2, 4, 6, 24, 48 hours post-infusion, and Days 4, 5, 8, and 15 post-infusion | PK parameters were calculated using standard non-compartmental methods. Vss of TAK-853, TAb and VZ/F of DM4 and S-methyl DM4 were reported at cycle 1 and cycle 3. |
| Number of Participants With Immunogenicity of TAK-853 | From start of study drug up to 8.2 months | Blood samples were collected to measure the presence of TAK-853 antibodies (ADA). Seronegative was defined as a participant with negative ADA at baseline and negative ADA at post-treatment. Treatment-emergent ADA was defined as a participant with negative ADA at baseline and positive ADA at post-treatment. Treatment-unaffected ADA was defined as a participant with positive ADA at baseline and post-dose titer increase that was less than or equal to 4-fold compared to baseline. Treatment-enhanced ADA was defined as a participant with positive ADA at baseline and post-dose titer increase that was greater than 4-fold compared to baseline. |
| Phase 2: Duration of Response (DOR) Assessed by Investigator With RECIST 1.1 | From first documented confirmed CR or PR until first documentation of PD (up to 7.2 months) | DOR was defined as the time from the first observation of CR/PR (whichever is first recorded) to the first date at which progressive disease is objectively documented per RECIST 1.1, or death due to any cause, whichever occurs first. DOR was estimated using the Kaplan-Meier method. |
| Phase 2: Plasma Concentrations of TAK-853 and TAb | Cycle 1 and 3: pre-infusion, 1-hour and Day 8 post-infusion | Plasma concentrations of TAK-853 and TAb were reported at cycle 1 and cycle 3. |
| Phase 2: Plasma Concentrations of DM4 and S-methyl DM4 | Cycle 1 and 3: pre-infusion, 1-hour and Day 8 post-infusion | Plasma concentrations of DM4 and S-methyl DM4 were reported at cycle 1 and cycle 3. |
Countries
Japan
Contacts
STUDY_DIRECTORStudy Director
Takeda
Participant flow
Recruitment details
Participants took part in the study at 15 investigative sites in Japan from 20 May 2024.
Pre-assignment details
A total of 28 participants were enrolled across two parts of the study. Three participants were enrolled in Phase 1, and twenty-five participants were enrolled in Phase 2. The study is currently ongoing. Results in this summary are reported based on the primary completion date (16 April 2025) of the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65.56 years STANDARD_DEVIATION 10.709 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 28 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 2 / 25 |
| other Total, other adverse events | 3 / 3 | 25 / 25 |
| serious Total, serious adverse events | 2 / 3 | 6 / 25 |
Outcome results
None listed