Phase 2 study with Infigratinib and personal experience with Infigratinib


Milind Javle, MD: In this pivotal infgratinib trial, recruited patients were treated extensively. In fact, only about a third had received 1 line of prior therapy, and the rest had received 2 or more lines of therapy. This was a heavily pre-treated population. They were treated with infigratinib, 125 mg per day for 3 weeks, 1 week off. The overall response rate in the trial was 23%. Interestingly, we noted that patients who received fewer lines of treatment had a better response rate compared to those who received 2 or more lines of treatment. Progression-free survival in this trial was 7 months, duration of response was 5 months, and overall survival extended beyond 12 months; it was a pivotal and positive trial. I just described the results of FOLFOX [folinic acid, fluorouracil, oxaliplatin] standard chemotherapy, which is relatively poor in comparison. As a result, this drug has obtained expedited approval from the FDA. The Fast Track Approval Mechanism is a conditional approval that requires a subsequent Phase 3 trial, which is ongoing at this time. This is called the PROOF test. Patients who have not received prior chemotherapy, treatment naïve patients, are treated with infigratinib vs gemcitabine and cisplatin as the first line. We are still awaiting the results of this trial, but it is very exciting that patients like the one described now have an FDA-approved option for the treatment of cholangiocarcinoma with infgratinib. This is now known as Truseltiq, which was only the second drug to be approved by the FDA for cholangiocarcinoma. It is certainly a historic event for the treatment of this disease.

At our institute, we were one of the primary sites for the CBGJ398X2204 trial which included infigratinib. We have treated several patients with this therapy. Most of these patients did quite well with progressive disease or partial responses. Some toxicities are encountered with this drug, but in general they are manageable. The most common toxicities include hyperphosphatemia or elevated phosphate levels, which should be carefully monitored and sometimes treated with dietary phosphate restriction and chelating agents. Other toxicities include anorexia, taste alteration, mucositis. There is a very low incidence of diarrhea, alopecia. The 2 important toxicities to watch out for are ocular. The most common eye toxicity is dry eye, but there are serious eye toxicities, including retinal pigment epithelial detachment and central serous retinopathy. These are again rare and mostly grade 1 or 2, but should be carefully monitored and monitored.

Transcription edited for clarity.

Case: 61-year-old woman with metastatic cholangiocarcinoma

May 2019

Initial presentation

  • A 61-year-old woman has jaundice and changes in the color of stool and urine.

Clinical assessment

  • Enlarged liver is palpable on physical examination
  • Blood tests show serum levels of CA 19-9 (1400 U / ml), bilirubin 2 mg / dL, ALT 550 U / L, AST 120U / L
  • Patient undergoes CT imaging and presents with multiple liver masses, consistent with metastatic disease or intrahepatic cholangiocarcinoma (iCCA)
  • Histopathological examination identifies adenocarcinoma, CK7 +, CK20-, HepPAR-, TTF- compatible with cholangiocarcinoma or upper GI Primary
  • The patient is diabetic and somewhat off-compliance with her diabetes medication
  • His ECOG PS is 1

July 2019


  • The patient is treated with chemotherapy (gemcitabine + cisplatin) for 24 weeks.
  • The progression of the disease is monitored every 2-3 months by CT imaging.

july 2020

  • The patient is doing well for 1 year after starting treatment, but now has elevated levels of CA 19-9.
  • The MRI shows several liver and bone lesions, but no signs of brain metastases.
  • Laboratory results are normal (absolute neutrophil count 4,000 / mm3, platelets 150,000 / ml, hemoglobin 12.1 g / dL
  • Patient undergoes NGS (Foundation Medicine, Inc.) test and found to have FGFR2-BICC1 gene fusion
  • The patient meets the eligibility criteria for the phase 2 study of infgratinib and is included in the trial and is treated with infigratinib
  • The patient shows no signs of disease progression on MRI for six months, suggesting stable disease, and CA19-9 levels remain within normal limits.

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