Toripalimab Plus Lenvatinib and Gemcitabine-based Chemotherapy in 1L Treatment of Advanced ICC: a Phase III Study

Summary

This is a Phase III, prospective, randomized, three-arm, double-blind, placebo-controlled, international multicenter study to evaluate the efficacy and safety of toripalimab in combination with lenvatinib and gemcitabine-based chemotherapy compared with gemcitabine-based chemotherapy as first-line treatment for unresectable advanced ICC.

This study will enroll approximately 480 patients with unresectable advanced ICC who have received no prior systemic therapy. Patients who meet the requirements will be randomly assigned to Treatment Arm A: Toripalimab, lenvatinib, and gemcitabine-based chemotherapy or Treatment Arm B: Toripalimab, oral placebo, and gemcitabine-based chemotherapy or Treatment Arm C: Intravenous placebo, oral placebo, and gemcitabine-based chemotherapy.

All patients will receive standard chemotherapy (GEMOX or GC per Investigator decision) for a maximum of 8 cycles. After the completion of standard chemotherapy, all patients continue to receive maintenance therapy with toripalimab injection or its placebo in combination with lenvatinib mesylate capsule or its placebo until unacceptable toxicity, confirmed disease progression and loss of clinical benefit as determined by the investigators, start of new anti-cancer therapy, death, other conditions requiring termination of study treatment, or the patient meets the criteria for study withdrawal, whichever occurs first.

In the absence of unacceptable toxicity, patients who meet criteria for unconfirmed disease progression per RECIST v1.1 while receiving toripalimab, lenvatinib, or their placebos will be permitted to continue treatment if their clinical status or symptoms are stable or improved (as determined by the investigators) or until loss of clinical benefit. Patients with confirmed disease progression should discontinue toripalimab, lenvatinib, or their placebos.

Tumor assessments will be performed at screening and during the study treatment per protocol. In the absence of progression, tumor assessments will continue as scheduled, regardless of whether study treatment ends, until confirmed disease progression or other criteria for study withdrawal are met, whichever occurs first. Patients who meet RECIST v1.1 criteria for progression should undergo tumor assessments as scheduled if clinical benefits of continuing study treatment are determined by investigators until progression is confirmed per iRECIST (iCPD), or the criteria for study withdrawal are met, whichever occurs first.

Computerized tomography (CT)/magnetic resonance imaging (MRI) scans for efficacy evaluation will be performed at baseline, every 6 weeks (Q6W) in the first year (52 weeks), and every 9 weeks (Q9W) in the second year (after week 52).

All AEs and concomitant medications during the study will be recorded. An end-of-treatment (EOT) visit will be performed within 30 days after the last dose of study treatment or termination of study treatment is confirmed by the investigator. After the EOT visit, follow-up for survival (telephone visit is allowed) will be conducted and AEs and subsequent anti-cancer therapy will be collected.

Conditions

• Intrahepatic Cholangiocarcinoma

Interventions

DRUG

Toripalimab

240 mg IV on day 1 of each 21-day treatment cycle (Q3W) for up to 35 treatment cycles

DRUG

Lenvatinib mesylate capsules

8 mg orally (po) once daily (QD)

DRUG

Placebo IV

Placebo IV on day 1 of each 21-day treatment cycle (Q3W) for up to 35 treatment cycles

DRUG

Oral placebo

Oral placebo po QD continuously

DRUG

Oxaliplatin for injection

85 mg/m2 IV, on day 1 of each 21-day treatment cycle (Q3W) up to 8 cycles

DRUG

Gemcitabine hydrochloride

1 g/m2 IV, on day 1 and day8 of each 21-day treatment cycle (Q3W) up to 8 cycles

DRUG

Cisplatin

25 mg/m2 IV, on day 1 and day8 of each 21-day treatment cycle (Q3W) up to 8 cycles

Sponsors & Collaborators

• Shanghai Junshi Bioscience Co., Ltd.

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-06-19

Primary Completion

2027-05-31

Completion

2027-05-31

Countries

• China

Study Locations