A Phase II Study of Pemigatinib Plus Durvalumab in Previously Treated Advanced Intrahepatic Cholangiocarcinoma Patients With FGFR-2 Fusion or Rearrangement

Inclusion Criteria

• •1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• •2. Age ≥ 18 years at the time of consent.
• •3. ECOG Performance Status of 0 or 1.
• •4. Body weight of \> 30 kg.
• •* Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
• •* Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with the study regimen may be included only after consultation with the sponsor-investigator.
• •10. Any concurrent chemotherapy, study drug, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• •11. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study regimen.
• •12. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study regimen. NOTE: Local surgery of isolated lesions for palliative intent is acceptable.
• •13. History of allogenic organ transplantation.
• •14. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• •* Patients with vitiligo or alopecia
• •* Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• •* Any chronic skin condition that does not require systemic therapy
• •* Patients without active disease in the last 5 years may be included but only after consultation with the sponsor-investigator
• •* Patients with celiac disease controlled by diet alone
• •15. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• •16. History of another primary malignancy except for
• •* Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of the study regimen and of low potential risk for recurrence
• •* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• •* Adequately treated carcinoma in situ without evidence of disease
• •17. History of leptomeningeal carcinomatosis
• •18. Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry. Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period or identified prior to signing the ICF. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤ 10mg/day of prednisone or its equivalent and anticonvulsants for at least 14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST Target Lesions at baseline.
• •19. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart).
• •20. History of active primary immunodeficiency
• •21. Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc). Participants with a past or resolved HBV infection (defined as the presence of antiHBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• •* Participants co-infected with HBV and HCV, or co-infected with HBV and HDV, namely: HBV positive (presence of HBsAg and/or anti HBcAb with detectable HBV DNA); AND
• •* HCV positive (presence of anti-HCV antibodies); OR
• •* HDV positive (presence of anti-HDV antibodies).
• •22. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies).
• •23. Known active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
• •24. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
• •* Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• •* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• •* Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• •25. Receipt of live vaccines or live attenuated vaccines within 30 days prior to the first dose of study regimen. NOTE: Patients, if enrolled, should not receive live vaccine whilst receiving study regimen and up to 90 days after the last dose of study regimen.
• •26. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control.
• •27. Known allergy or hypersensitivity to any of the study regimen medications or any of the study regimen medication excipients.
• •28. Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
• •29. Patients who have received prior anti-PD-1, anti PD-L1:
• •* Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
• •* All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
• •* Must not have experienced a ≥ Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤ Grade 2 are permitted to enrol if they are stably maintained on appropriate replacement therapy and are asymptomatic.
• •* Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day.
• •30. Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.