| Eligibility |
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.
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
Exclusion Criteria:
Phase 1 part:
1. Participant with > Grade 1 peripheral neuropathy per National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
2. 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.
3. Serious concurrent illness, including, but not limited to the following:
1. Clinically relevant active infection including - Active hepatitis B or C
infection (whether or not on active antiviral therapy)
- Human Immunodeficiency Virus (HIV) infection
- Active cytomegalovirus infection
- Active COVID-19/SARS-CoV-2 infection. Although SARS-CoV-2 testing is not
mandatory for study entry, testing should follow local clinical practice
guidelines and standards
- Any other known concurrent infectious disease requiring IV antibiotics within 2
weeks before starting study drug Note: Testing at screening for hepatitis is
required, while not required for the remaining infections above unless clinically
indicated. Participants with known hepatitis B surface antigen seropositivity
and/or detectable hepatitis C virus RNA will be excluded. Participants who have
positive hepatitis B core antibody and/or hepatitis B surface antibody can be
enrolled but must have an undetectable serum hepatitis B virus DNA. Participants
who have positive hepatitis C virus antibody must have an undetectable hepatitis
C virus RNA serum level. Participants will be monitored and managed according to
Guideline for the prevention of immunosuppressive therapy or chemotherapy-induced
reactivation of hepatitis B virus infection (The Japan Society of Hepatology
2022).
2. Participants with clinically significant cardiac disease including, but not
limited to, any one of the following:
- Myocardial infarction =< 6 months prior to first dose of study medication
- Unstable angina pectoris
- Uncontrolled congestive heart failure (New York Heart Association > class II)
- Uncontrolled >= Grade 3 hypertension (per NCI CTCAE v5.0)
- Uncontrolled cardiac arrhythmias
- Severe aortic stenosis
- >= Grade 3 cardiac toxicity following prior chemotherapy
3. History of multiple sclerosis or other demyelinating disease, Lambert-Eaton
syndrome (paraneoplastic syndrome), history of hemorrhagic or ischemic stroke
within the last six months, or alcoholic liver disease.
4. Previous clinical diagnosis of interstitial lung disease (ILD), including
pneumonitis.
4. Any other concomitant anti-cancer treatment such as immunotherapy, biotherapy,
radiotherapy, chemotherapy, investigative therapy, or high-dose steroids; however,
low-dose steroids and Luteinizing Hormone Releasing Hormone (LHRH) at doses that have
been stable for >= 14 days are permitted for participants with prostate cancer
5. Known hypersensitivity to previous monoclonal antibody therapy or maytansinoids, or
study drugs and/or any of their excipients
6. Prior history of solid tumor malignancy within the last 3 years except for adequately
treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ
breast cancer, in situ prostate cancer (participants must have shown no evidence of
active disease for 2 years prior to enrollment)
7. Participants with required use of folate-containing supplements (e.g., folate
deficiency)
8. Participants who have received prior allogeneic or autologous bone marrow transplants
Phase 2 part:
1. Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed
tumors containing any of the above histologies, or low-grade or borderline ovarian
tumor
2. Participants with primary platinum-refractory disease, defined as disease that did not
respond to (CR or PR) or has progressed within 3 months of the last dose of first line
platinum-containing chemotherapy
3. Participants with prior wide-field radiotherapy affecting at least 20% of the bone
marrow
4. Participants with > Grade 1 peripheral neuropathy per NCI CTCAE v5.0
5. 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
6. 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. HIV infection
3. Active cytomegalovirus infection
4. Active COVID-19/SARS-CoV-2 infection. Although SARS-CoV-2 testing is not
mandatory for study entry, testing should follow local clinical practice
guidelines and standards.
5. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks
before starting study drug Note: Testing at screening for hepatitis (a) is
required, while not required for the remaining infections above (b-e) unless
clinically indicated.
Participants with known hepatitis B surface antigen seropositivity and/or detectable
hepatitis C virus RNA will be excluded. Participants who have positive hepatitis B core
antibody and/or hepatitis B surface antibody can be enrolled but must have an undetectable
serum hepatitis B virus DNA.
Participants who have positive hepatitis C virus antibody must have an undetectable
hepatitis C virus RNA serum level. Participants will be monitored and managed according to
Guideline for the prevention of immunosuppressive therapy or chemotherapy-induced
reactivation of hepatitis B virus infection (The Japan Society of Hepatology 2022).
7. Participants with history of multiple sclerosis or other demyelinating disease and/or
Lambert-Eaton syndrome (paraneoplastic syndrome) 8. Participants with clinically
significant cardiac disease including, but not limited to, any one of the following:
1. Myocardial infarction =< 6 months prior to first dose of study medication
2. Unstable angina pectoris
3. Uncontrolled congestive heart failure (New York Heart Association > class II)
4. Uncontrolled >= Grade 3 hypertension (per NCI CTCAE v5.0)
5. Uncontrolled cardiac arrhythmias 9. Participants with a history of hemorrhagic or
ischemic stroke within six months prior to first dose of TAK-853 10. Participants with
a history of cirrhotic liver disease (Child-Pugh Class B or C) 11. Participants with a
previous clinical diagnosis of ILD, including pneumonitis 12. Participants with
required use of folate-containing supplements (e.g., folate deficiency) 13.
Participants with prior hypersensitivity to monoclonal antibodies or maytansinoids 14.
Participants with prior treatment with TAK-853 or other FR alpha-targeting agents 15.
Participants with untreated or symptomatic CNS metastases 16. Participants with a
history of other malignancy within 3 years prior to first dose of TAK-853 Note: does
not include tumors with a negligible risk for metastasis or death (e.g., adequately
controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma
in situ of the cervix or breast) 17. Prior known hypersensitivity reactions to study
drugs and/or any of their excipients
|
