Phase I/II Trial of Pemigatinib in Combination With Atezolizumab and Bevacizumab for Treatment of Advanced Cholangiocarcinoma With FGFR2 Fusion

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

To learn if pemigatinib in combination with atezolizumab and bevacizumab can help to control cholangiocarcinoma.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Ability to understand and willingness to sign informed consent.

• 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, as 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 and 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) ≥ 1.5 × 109/L (1000/µL) without granulocyte colony-stimulating factor support

• Platelet count ≥ 100 × 109/L (100,000/µL) without transfusion

• Hemoglobin ≥ 90 g/L (9 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. For patients on anticoagulation, those on therapeutic anticoagulation over 2 weeks are eligible.

• 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.

• 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: Single-dose studies Small Molecules: 5 elimination half-lives or 14 days after the last dose, whichever is longer Large Molecules: 2 elimination half-lives or 28 days after the last dose, whichever is longer Multiple-dose studies Small Molecules: 5 elimination half-lives or 28 days after the last dose, whichever is longer Large Molecules: 2 elimination half-lives or 28 days after the last dose, whichever is longer 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.

Locations
United States
Texas
MD Anderson Cancer Center
RECRUITING
Houston
Contact Information
Primary
Sunyoung Lee, MD,PHD
GIClinicalTrials@mdanderson.org
(713) 792-2828
Time Frame
Start Date: 2024-11-19
Estimated Completion Date: 2030-02-22
Participants
Target number of participants: 25
Treatments
Experimental: Part 1
Participants enrolled in Part 1, the dose of pemigatinib the participant receive will depend on when the participant join this study. Up to 2 dose levels of pemigatinib will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the highest dose level of pemigatinib. A second group will receive a lower dose of pemigatinib than the group before it, if intolerable side effects are seen.
Experimental: Part 2
Participants in Part 2, you will receive pemigatinib at the recommended dose that was found in Part 1.
Related Therapeutic Areas
Sponsors
Leads: M.D. Anderson Cancer Center
Collaborators: Genentech, Inc., Incyte Corporation

This content was sourced from clinicaltrials.gov