Trial Title:
Phase II Trial of Pemigatinib in Combination With Atezolizumab and Bevacizumab for Treatment of Advanced Cholangiocarcinoma With FGFR2 Fusion
NCT ID:
NCT06439485
Condition:
Advanced Cholangiocarcinoma
FGFR2 Fusion
Conditions: Official terms:
Cholangiocarcinoma
Bevacizumab
Atezolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pemigatinib
Description:
Given by PO
Arm group label:
Part 1
Arm group label:
Part 2
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
Given by PO and IV
Arm group label:
Part 1
Arm group label:
Part 2
Other name:
MPDL3280A
Other name:
TECENTRIQ
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
Given by PO and IV
Arm group label:
Part 1
Arm group label:
Part 2
Other name:
Avastin™
Other name:
Anti-VEGF monoclonal antibody
Other name:
rhuMAb-VEGF
Summary:
To learn if pemigatinib in combination with atezolizumab and bevacizumab can help to
control cholangiocarcinoma.
Detailed description:
Primary Objectives:
• To assess the antitumor activity of the treatment combinations based on objective
response rate (ORR) Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. This
assessment will be confirmed in the next scheduled scan.
Secondary Objectives:
1. To determine the safety and recommended phase 2 dose (RP2D) of the triple
combination of pemigatinib with bevacizumab and atezolizumab in participants with
FGFR-altered metastatic CCA.
2. To evaluate the duration of response in participants with best overall response of
complete response (CR) or partial response (PR).
3. To evaluate PFS defined as the time from the start of study treatment to disease
progression or death, whichever occurs first.
4. To evaluate the duration of OS defined as the time from the start of study treatment
to death from any cause.
5. To evaluate the clinical benefit rate defined as the proportion of participants with
best overall response of CR, PR, or stable disease.
6. To evaluate safety and endpoints 2-5 with the doublet of pemigatinib with
atezolizumab.
Exploratory Objectives:
• To examine the change of the immune microenvironment on treatment by the combination
using a validated immune biomarker panel and end-of-treatment genomic markers using cfDNA
to study resistance to pemigatinib and response markers from trial medications.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Ability to understand and willingness to sign a written informed consent document
for participation in this trial. Individuals lacking the ability, based on
reasonable medical judgment, to understand and appreciate the nature and
consequences of participation in this study will not be eligible for participation.
- Age ≥18 years.
- Has histologically confirmed metastatic or advanced unresectable cholangiocarcinoma.
- Has disease that is measurable per the RECIST v1.1.
- Has at least one measurable target lesion.
- Has FGFR2 fusion or rearrangement in tumor tissue. Presence of the FGFR2 fusion and
rearrangement should be determined by CLIA-validated genomic testing of a tumor
tissue specimen (DNA-based or RNA-based).
- Is refractory to, has demonstrated intolerance to, had received, or has refused
access to, the 1st line systemic therapy including gemcitabine-based therapy with or
without immunotherapy including durvalumab or pembrolizumab. Participants who
discontinued available standard therapy due to toxicity must have continued evidence
of measurable disease.
- Has available a formalin-fixed, paraffin-embedded primary tumor sample.
- Is able to take oral medication.
- Is able to comply with protocol procedures and scheduled visits.
- Has Eastern Cooperative Oncology Group performance status of 0 or 1
- Has adequate hematologic and end-organ function, defined by the following laboratory
test results, obtained within 14 days prior to initiation of study treatment:
- Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (1000/µL) without granulocyte
colony-stimulating factor support
- Platelet count ≥ 75 × 109/L (75,000/µL) without transfusion
- Hemoglobin ≥ 80 g/L (8 g/dL)
- Participants may be transfused to meet this criterion.
- Aspartate amino transferate (AST), alanine aminotransferase (ALT), and alkaline
phosphatase (ALP) ≤ 2.5 × upper limit of normal (ULN), with the following
exceptions:
- Participants with documented liver metastases: AST and ALT ≤ 5 × ULN
- Participants with documented liver or bone metastases: ALP ≤ 5 × ULN
- Serum bilirubin ≤ 1.5 × ULN with the following exception:
- Participants with known Gilbert disease: serum bilirubin ≤ 3 × ULN
- Serum creatinine ≤ 1.5 × ULN
- Serum albumin ≥ 25 g/L (2.5 g/dL)
- For participants not receiving therapeutic anticoagulation: international
normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 ×
ULN
- Has a negative human immunodeficiency virus (HIV) test at screening with the
following exception: participants with a positive HIV test at screening are eligible
provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200 and have
an undetectable viral load
- Has a negative hepatitis B surface antigen (HBsAg) test at screening (unless
participant has chronic HBV on anti-viral therapy)
- Has a negative total hepatitis B core antibody (HBcAb) test at screening, or
positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at
screening (unless patient has chronic HBV on anti-viral therapy)
- The HBV DNA test will be performed only for participant who have a negative HBsAg
test and a positive total HBcAb test.
- Participants with chronic HBV on antiviral therapy or HCV participants who have
completed curative anti-viral therapy can be included. Requirements for
contraception and pregnancy testing for a clinical trial should encompass all
investigational medicinal products (IMPs) as well as protocol-mandated
non-investigational medicinal products (NIMPs) such as background therapy, and the
measures to be followed should be based on the medicinal product with the highest
risk (see the protocol synopsis for definition of IMP and NIMP). Contraception
requirements for marketed Roche IMPs or NIMPs should be based on recommendations in
the Summary of Product Characteristics or, if there is no Summary of Product
Characteristics, national prescribing information. Length of time required for
abstinence or use of contraceptives should take into account the reproductive
toxicity profile, including genotoxicity and teratogenicity, the size of the
molecule, and the number of doses. In the absence of specific delayed-toxicity
concerns or safety hypotheses, the following guidelines should be used:
Options for female contraception are based on the Clinical Trial Facilitation Group
"Recommendations related to contraception and pregnancy testing in clinical trials."
Three options for female contraception are shown below.
• For women of childbearing potential: agrees to remain abstinent (refrain from
heterosexual intercourse) or to use contraceptive methods, and agrees to refrain from
donating eggs, as defined below:
- Women must remain abstinent or use contraceptive methods with a failure rate of < 1%
per year during the treatment period and for 6 months after the final dose of
atezolizumab/pemigatinib/bevacizumab. Women must refrain from donating eggs during
this same period.
- A woman is considered to be of childbearing potential if she is postmenarchal, has
not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no
identified cause other than menopause), and has not undergone surgical sterilization
(removal of ovaries and/or uterus). The definition of childbearing potential may be
adapted for alignment with local guidelines or requirements.
- Examples of contraceptive methods with a failure rate of < 1% per year include
bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit
ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
- The reliability of sexual abstinence should be evaluated in relation to the duration
of the clinical trial and the preferred and usual lifestyle of the participant.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods)
and withdrawal are not adequate methods of contraception. Options for contraception in
male patients with pregnant female partners and/or with female partners of childbearing
potential are based on the Clinical Trial Facilitation Group "Recommendations related to
contraception and pregnancy testing in clinical trials" and the Roche White Paper
regarding contraception for males in clinical trials.
Atezolizumab does not require male contraception or condom use; guidelines below apply to
other protocol-mandated study treatments.
• For men: agrees to remain abstinent (refrain from heterosexual intercourse) or use a
condom, and agrees to refrain from donating sperm, as defined below:
- With a female partner of childbearing potential or pregnant female partner, men must
remain abstinent or use a condom during the treatment period and for 6 months after
the final dose of atezolizumab/pemigatinib/bevacizumab to avoid exposing the embryo.
Men must refrain from donating sperm during this same period.
- The reliability of sexual abstinence should be evaluated in relation to the duration
of the clinical trial and the preferred and usual lifestyle of the participant.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods)
and withdrawal are not adequate methods of preventing drug exposure.
Exclusion Criteria:
- Received prior chemotherapy, biologic therapy, immunotherapy, or investigational
agent within 3 weeks prior to initiation of study medications.
- Had previous treatment with selective FGFR inhibitors including erdafitinib,
infigratinib, or futibatinib.
- Had prior therapy with any VEGFR-targeting agent targeting including bevacizumab,
ramucirumab, pazopanib, lenvatinib, and other anti-angiogenesis inhibitors.
- Has a history and/or has current evidence of extensive tissue calcification
including, but not limited to, the soft tissue, kidneys, intestine, myocardium,
vascular system, and lung. Exceptions include calcified lymph nodes, minor pulmonary
parenchymal calcifications, and asymptomatic coronary calcifications-these are
allowed.
- Has corneal or retinal disorder/keratopathy with current evidence of corneal or
retinal disorder/keratopathy including, but not limited to, bullous/band
keratopathy, inflammation, or ulceration, keratoconjunctivitis, or diabetic
retinopathy, confirmed by ophthalmic physician. Participants with asymptomatic
ophthalmic conditions assessed by the investigator to pose minimal risk for study
participation may be enrolled in the study.
- Are currently receiving or are planning to receive during participation in this
study, treatment with any potent CYP3A4 inhibitors or inducers or moderate CYP3A4
inducers within 14 days or 5 half-lives (whichever is longer) before the first dose
of study drug. Moderate CYP3A4 inhibitors are not prohibited but should be avoided.
Medications that increase serum phosphorus and/or calcium concentration are
prohibited. Medications associated with hyperphosphatemia and/or hypercalcemia
adverse events are searchable in the Leximcomp Online Pharmacy & Formulary available
on the Inside MD Anderson Clinical Tools SharePoint site. Participants are not
permitted to receive enzyme-inducing anti-epileptic drugs, including carbamazepine,
phenytoin, phenobarbital, and primidone.
- Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star
fruits, pomelos, Seville oranges or products containing juice of these fruits within
7 days prior to first dose of study drug.
- Had a Grade 3-4 gastrointestinal bleed within 3 months prior to enrollment.
- Has a history of deep vein thrombosis, pulmonary embolism, or any other
thromboembolism, including portal venous thrombosis within 3 months prior to
enrollment. Venous port or catheter thrombosis, incidental asymptomatic pulmonary
embolism diagnosed on imaging studies, or superficial venous thrombosis are not
considered significant and are allowed.
- Has current or recent (within 10 days prior to study treatment start) use of
full-dose oral or parenteral anticoagulants (including direct oral anticoagulants);
thrombolytic agents for therapeutic (as opposed to prophylactic) purpose; use of
aspirin (> 325 mg/day); or use of clopidogrel (> 75 mg/day). Prophylactic
anticoagulation for the patency of venous access devices is allowed provided the
activity of the agent results in an INR <1.5 × ULN and an aPTT within normal limits
within 14 days prior to initiation of study treatment.
- Had significant cardiovascular disease (such as New York Heart Association Class II
or greater cardiac disease, myocardial infarction, transient ischemic attack or
cerebrovascular accident); unstable arrhythmia; or unstable angina significant
cardiovascular disease within 6 months prior to enrollment.
- Has a history of uncontrolled or poorly-controlled hypertension (>150 mmHg systolic
or >100 mmHg diastolic).
- Has a history of hypertensive crisis or hypertensive encephalopathy.
- Had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to
enrollment.
- Has undergone major surgery (including open biopsy, surgical resection, wound
revision; or any other major surgery involving entry into a body cavity); or
significant traumatic injury within 28 days prior to enrollment; or subcutaneous
venous-access-device placement within 7 days prior to enrollment; or anticipates
need for major surgical procedure, core biopsy, or other minor surgical procedures
during the course of the study.
o Note: Placement of a vascular access device should be at least 2 days prior to
initiation of study treatment.
- Is receiving chronic antiplatelet therapy, nonsteroidal anti-inflammatory drugs
(e.g., ibuprofen, naproxen), dipyridamole, clopidogrel, or similar agents.
Once-daily aspirin use (≤325 mg/day) is allowed.
- Is pregnant or breastfeeding.
- Has had significant vascular disease (e.g., aortic aneurysm requiring surgical
repair or recent arterial thrombosis) within 6 months prior to randomization.
- Has a history of central nervous system disease or evidence of this disease upon
physical or neurological examination.
- Has a history of Grade ≥ 2 hemoptysis (defined as ≥ 2.5 mL of bright red blood per
episode) within 1 month prior to screening.
- Has a history or evidence of inherited bleeding diathesis or significant
coagulopathy at risk of bleeding (i.e., in the absence of therapeutic
anticoagulation).
- Has a history of abdominal fistula, gastrointestinal (GI) perforation,
intra-abdominal abscess, or active GI bleeding within 6 months prior to
randomization.
- Has a history of leptomeningeal disease.
- Has uncontrolled tumor-related pain.
- Symptomatic lesions (e.g., bone metastases or metastases causing nerve
impingement) amenable to palliative radiotherapy should be treated prior to
enrollment. Participants should have recovered from the effects of radiation.
There is no required minimum recovery period.
- Asymptomatic metastatic lesions that would likely cause functional deficits or
intractable pain with further growth (e.g., epidural metastasis that is not
currently associated with spinal cord compression) should be considered for
loco-regional therapy, if appropriate, prior to enrollment.
- Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring
recurrent drainage procedures (at a frequency of at least once monthly)
o Participants with indwelling catheters (e.g., PleurX®) are allowed. Has
uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium >
12 mg/dL, or corrected serum calcium > ULN).
- Has current evidence of endocrine alterations of calcium/phosphate homeostasis, eg,
parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral
calcinosis, and other disorders.
- Has elevated phosphorus or abnormal serum calcium, or phosphorus, or
calcium-phosphorus product ≥ 55 mg2/dL2:
- Inorganic phosphorus > 1.02 × ULN Has active or a history of autoimmune disease
or immune deficiency, including, but not limited to, myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid
arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome,
Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple
sclerosis (see Appendix 9 for full list), with the following exceptions:
- Participants with a history of autoimmune-related hypothyroidism who are on
thyroid-replacement hormone are eligible for the study.
Participants with controlled Type 1 diabetes mellitus (as determined by the treating
physician) who are on an insulin regimen are eligible for the study.
- Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., participants with psoriatic arthritis are
excluded) are eligible for the study provided all of following conditions are met:
- Rash must cover < 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical
corticosteroids
- No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet-A radiation, methotrexate, retinoids, biologic
agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids
within the previous 12 months
- Has a history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g.,
bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis;
or has evidence of active pneumonitis upon screening via computed tomography
(CT) scan of the chest.
- History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Has active tuberculosis.
- Had a major surgical procedure, other than for diagnosis, within 4 weeks prior
to initiation of study treatment, or anticipates need for a major surgical
procedure during the study.
- Had a history of malignancy other than cholangiocarcinoma within 2 years prior
to screening, with the exception of malignancies with a negligible risk of
metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated
carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate
cancer, ductal carcinoma in situ, or Stage I uterine cancer.
- Had a severe infection within 4 weeks prior to initiation of study treatment,
including, but not limited to, hospitalization for complications of infection,
bacteremia, or severe pneumonia.
- Received treatment with therapeutic oral- or IV antibiotics within 2 weeks
prior to initiation of study treatment.
- Participants receiving prophylactic antibiotics (e.g., to prevent a urinary tract
infection or chronic obstructive pulmonary disease exacerbation) are eligible for
the study.
- Had a prior allogeneic stem cell or solid organ transplantation
- Has any other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding that contraindicates the use of an investigational
drug, that may affect the interpretation of the results, or that may render the
patient at high risk from treatment complications.
- Received treatment with a live, attenuated vaccine within 4 weeks prior to
initiation of study treatment, or anticipates need for such a vaccine during
treatment or within 5 months after the final dose of treatment. Receipt of
SARS-CoV vaccine is allowed.
- Received treatment with systemic immunostimulatory agents (including, but not
limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives
of the drug (whichever is longer) prior to initiation of study treatment.
- Received treatment with systemic immunosuppressive medication (including, but
not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate,
thalidomide, or anti-TNF-α agents) within 2 weeks prior to initiation of study
treatment, or anticipates a need for systemic immunosuppressive medication
during study treatment, with the following exceptions:
- Participants who received acute, low-dose systemic immunosuppressant medication or a
one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of
corticosteroids for a contrast allergy) are eligible for the study after Principal
Investigator confirmation has been obtained.
- Participants who received mineralocorticoids (e.g., fludrocortisone),
corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose
corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible
for the study.
- Has a history of severe allergic anaphylactic reactions to chimeric or
humanized antibodies or fusion proteins.
- Has a known hypersensitivity to Chinese hamster ovary-cell products or to any
component of the atezolizumab formulation.
- Has a known allergy or hypersensitivity to any component of the pemigatinib,
bevacizumab, or atezolizumab formulations.
- Is pregnant or breastfeeding or intends to become pregnant during study
treatment or within 6 months after the final dose of study treatment.
- Women of childbearing potential must have a negative serum pregnancy test result
within 14 days prior to initiation of study treatment.
- Has a history of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000
UI/weekly) to replenish the deficiency. Vitamin D supplements are allowed.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Contact:
Last name:
Sunyoung Lee, MD,PHD
Phone:
713-792-8501
Email:
sslee1@mdanderson.org
Investigator:
Last name:
Sunyoung Lee, MD,PHD
Email:
Principal Investigator
Start date:
November 29, 2024
Completion date:
February 22, 2030
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Incyte Corporation
Agency class:
Industry
Collaborator:
Agency:
Genentech, Inc.
Agency class:
Industry
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06439485
http://www.mdanderson.org
