Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)

Inclusion Criteria:

1. Be ≥18 years of age.

2. Have a histopathological diagnosis (fresh or banked tumor biopsy sample, preferably
collected within the last 3 years) of nonresectable or metastatic cholangiocarcinoma
and are not eligible for curative resection, transplantation, or ablative therapies.

3. Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most
recent banked tumor tissue available) based on central laboratory testing
(R132C/L/G/H/S mutation variants tested).

4. Have an ECOG PS score of 0 or 1

5. Have an expected survival of ≥3 months.

6. Have at least one evaluable and measurable lesion as defined by RECIST v1.1. Subjects
who have received prior local therapy (including but not limited to embolization,
chemoembolization, radiofrequency ablation, or radiation therapy) are eligible
provided measurable disease falls outside of the treatment field or within the field
and has shown ≥20% growth in size since post-treatment assessment.

7. Have documented disease progression following at least 1 and no more than 2 prior
systemic regimens for advanced disease (nonresectable or metastatic). Subjects must
have received at least 1 gemcitabine- or 5-FU-containing regimen for advanced
cholangiocarcinoma. Subjects who have received systemic adjuvant chemotherapy will be
permitted provided there is documented disease progression during or within 6 months
of completing the therapy.

Exclusion criteria:

1. Received a prior IDH inhibitor.

2. Received systemic anticancer therapy or an investigational agent <2 weeks prior to Day
1 (washout from prior immune based anticancer therapy is 4 weeks). In addition, the
first dose of study treatment should not occur before a period ≥5 half-lives of the
investigational agent has elapsed.

3. Received radiotherapy to metastatic sites of disease <2 weeks prior to Day 1.

4. Underwent hepatic radiation, chemoembolization, and radiofrequency ablation <4 weeks
prior to Day 1.

5. Have known symptomatic brain metastases requiring steroids. Subjects with previously
diagnosed brain metastases are eligible if they have completed their treatment and
have recovered from the acute effects of radiation therapy or surgery prior to study
entry, have discontinued corticosteroid treatment for these metastases for at least 4
weeks and have radiographically stable disease for at least 3 months prior to study
entry. Note: up to 10 mg per day of prednisone equivalent will be allowed.