A Phase I/II Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)

• Status: Not yet recruiting
• Trial end date: 2042-06-01

Summary

Background:

Advanced biliary tract carcinoma (BTC) has limited treatment options in the second line setting and a dismal prognosis.

Capecitabine and oxaliplatin (CAPOX) in combination with Keytruda is a tolerable and potentially effective treatment for patients with refractory advanced BTC.

Programmed cell death protein 1 (PD-1) is an inhibitory receptor that is expressed by all Tcells during activation. It regulates T-cell effector functions during various physiological responses, including acute and chronic infection, cancer and autoimmunity, and immune

homeostasis. Keytruda is a programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of different cancers including patients with hepatocellular carcinoma.

CD40-mediated activation of macrophages and dendritic cells (DC)s in intrahepatic cholangiocarcinoma (iCCA) significantly improves response to anti-PD-1 therapy in preclinical studies. The efficacy of this regimen is enhanced by first-line chemotherapy,

supporting the potential antitumor efficacy of the combination of CD40 agonist antibody (anti-CD40) with anti-PD-1 and chemotherapy.

Objectives:

Phase I: To estimate safe dose of CDX-1140 used in combination with CAPOX, and Keytruda (R)

Phase II:

To evaluate the 6-month progression free survival (PFS) in participants with advanced BTC treated with CDX-1140, CAPOX, and Keytruda (R).

To determine the overall response rate (ORR) defined as complete response (CR) + partial response (PR) according to RECIST 1.1 in participants with advanced BTC.

Eligibility:

Histopathological confirmation of BTC or histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology,are highly suggestive of a diagnosis of BTC

Age >=18 years

Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Design:

Phase I/II, single-arm, non-randomized trial of Keytruda(R) and CDX-1140 in combination with CAPOX in participants with BTC in the second-line setting.

Initially, 9-12 participants will be enrolled into a Phase I portion of the trial. If safe, we will continue enrollment as planned into Phase II, if not, we will close the protocol.

After estimation of CDX-1140 recommended phase II dose, the first 13 participants enrolled at this dose level of CDX-1140 in Phase I and Phase II will be evaluated forprogression. If among these 13 participants, no more than 2 can be progression-free at the 6-months evaluation, then no further participants will be enrolled as soon as this can be determined.

• Phase: Phase 1/Phase 2

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Capecitabine; Oxaliplatin; Pembrolizumab