Phase Ib/II Study of INC280 + PDR001 or PDR001 Single Agent in Advanced HCC

NCT ID: NCT02795429

Last Updated: 2023-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-15
• Study Completion Date: 2021-06-24

Brief Summary

The purpose of this study of capmatinib (INC280) and spartalizumab (PDR001) was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of spartalizumab administered intravenously (i.v.) as a single agent or in combination with capmatinib administered orally in adult patients with advanced hepatocellular carcinoma (HCC).

Detailed Description

This was a Phase Ib/II, open label, multicenter study starting with a Phase Ib dose escalation part followed by a randomized Phase II part in patients with advanced hepatocellular carcinoma. Capmatinib was administered orally twice daily (BID) and spartalizumab was administered i.v. every 3 weeks (Q3W) until the occurrence of unacceptable toxicity, progressive disease as per irRC and/or treatment was discontinued at the discretion of the Investigator or the participant. A complete cycle of treatment was defined as 21 days.

During the Phase Ib dose escalation part of the study, participants were treated with capmatinib in combination with a fixed dose of spartalizumab until the maximum tolerated dose (MTD) was reached or the recommended phase 2 dose (RP2D) was established. The capmatinib dose was increased and the spartalizumab dose remained constant.

Once the MTD and/or RP2D were declared for capmatinib in combination with spartalizumab, additional participants were enrolled in the Phase II part in order to assess the anti-tumor activity of capmatinib in combination with spartalizumab and spartalizumab single agent. Participants were randomly assigned, in a 1:1 ratio, to treatment with either capmatinib in combination with spartalizumab or spartalizumab single agent.

Conditions

Advanced Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase Ib: Capmatinib 200 mg BID + Spartalizumab 300 mg Q3W

Capmatinib 200 mg administered orally on a continuous twice daily (BID) dosing schedule in combination with spartalizumab 300 mg administered intravenously once every 3 weeks (Q3W) in Phase Ib

Group Type: EXPERIMENTAL

Spartalizumab

Intervention Type: DRUG

Spartalizumab administered via intravenous (i.v.) infusion once every 3 weeks (Q3W)

Capmatinib

Intervention Type: DRUG

Capmatinib administered orally as a tablet on a continuous twice daily (BID) dosing schedule

Phase Ib: Capmatinib 300 mg BID + Spartalizumab 300 mg Q3W

Capmatinib 300 mg administered orally on a continuous twice daily (BID) dosing schedule in combination with spartalizumab 300 mg administered intravenously once every 3 weeks (Q3W) in Phase Ib

Group Type: EXPERIMENTAL

Spartalizumab

Intervention Type: DRUG

Spartalizumab administered via intravenous (i.v.) infusion once every 3 weeks (Q3W)

Capmatinib

Intervention Type: DRUG

Capmatinib administered orally as a tablet on a continuous twice daily (BID) dosing schedule

Phase Ib: Capmatinib 400 mg BID + Spartalizumab 300 mg Q3W

Capmatinib 400 mg administered orally on a continuous twice daily (BID) dosing schedule in combination with spartalizumab 300 mg administered intravenously once every 3 weeks (Q3W) in Phase Ib

Group Type: EXPERIMENTAL

Spartalizumab

Intervention Type: DRUG

Spartalizumab administered via intravenous (i.v.) infusion once every 3 weeks (Q3W)

Capmatinib

Intervention Type: DRUG

Capmatinib administered orally as a tablet on a continuous twice daily (BID) dosing schedule

Phase II: Capmatinib 400 mg BID + Spartalizumab 300 mg Q3W

Capmatinib 400 mg administered orally on a continuous twice daily (BID) dosing schedule in combination with spartalizumab 300 mg administered intravenously once every 3 weeks (Q3W) in Phase II

Group Type: EXPERIMENTAL

Spartalizumab

Intervention Type: DRUG

Spartalizumab administered via intravenous (i.v.) infusion once every 3 weeks (Q3W)

Capmatinib

Intervention Type: DRUG

Capmatinib administered orally as a tablet on a continuous twice daily (BID) dosing schedule

Phase II: Spartalizumab 300 mg Q3W

Spartalizumab 300 mg administered intravenously once every 3 weeks (Q3W) in Phase II

Group Type: EXPERIMENTAL

Spartalizumab

Intervention Type: DRUG

Spartalizumab administered via intravenous (i.v.) infusion once every 3 weeks (Q3W)

Interventions

Spartalizumab

Spartalizumab administered via intravenous (i.v.) infusion once every 3 weeks (Q3W)

Intervention Type: DRUG

Capmatinib

Capmatinib administered orally as a tablet on a continuous twice daily (BID) dosing schedule

Intervention Type: DRUG

Other Intervention Names

PDR001; INC280

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically documented locally advanced recurrent or metastatic HCC or for patients with cirrhosis according to the American Association for the Study of Liver Diseases (AASLD) and Asian Pacific Association for the study of the liver (APASL) criteria. Current cirrhotic status of Child Pugh Class A (5-6 points), with no encephalopathy and/or clinically significant ascites (defined as requiring the use of diuretics or paracentesis treatment).

2. Patients must have received prior systemic sorafenib treatment for HCC with documented progression during or after discontinuation of sorafenib treatment (for France only: patients must have received at least 8 weeks of prior sorafenib treatment), or are intolerant to sorafenib (defined as documented Grade 3 or 4 adverse events that led to sorafenib discontinuation),.

3. ECOG Performance Status ≤ 1.

4. Willing and able to swallow and retain oral medication.

Exclusion Criteria

1. Use of any live vaccines within 4 weeks of initiation of study treatment.

2. History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).

3. Clinically significant pleural effusion that either required pleurocentesis or is associated with shortness of breath.

4. Active autoimmune disease or a documented history of autoimmune disease.

5. Clinically significant, uncontrolled heart diseases.

6. Patient having out of range laboratory values defined as:

• Total bilirubin > 2 mg/dL, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
• Alanine aminotransferase (ALT) > 5 x ULN
• Aspartate aminotransferase (AST) > 5 x ULN
• Coagulation: Prothrombin Time (PT) > 4 seconds more than the ULN or International Normalized Ratio (INR) > 1.7
• Absolute neutrophil count (ANC) < 1.5 x 109/L
• Platelet count < 75 x 109/L
• Hemoglobin < 9 g/dL
• Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 45 mL/min
• Asymptomatic serum amylase grade > 2 (1.5-2.0 x ULN). Patients with grade 1 or grade 2 serum amylase at the beginning of the study must be confirmed to have no signs or symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging findings of pancreas, etc.)
• Serum lipase > ULN
• Potassium, Magnesium, Phosphorus, total Calcium (corrected for serum albumin) outside of normal limits (patients may be enrolled if corrected to within normal limits with supplements during screening)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Guangzhou, Guangdong, China

Novartis Investigative Site

Shanghai, Shanghai Municipality, China

Novartis Investigative Site

Montpellier, Herault, France

Novartis Investigative Site

Lille, , France

Novartis Investigative Site

Toulouse, , France

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Würzburg, , Germany

Novartis Investigative Site

Hong Kong, , Hong Kong

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Rozzano, MI, Italy

Novartis Investigative Site

Modena, MO, Italy

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Tainan City, , Taiwan

Novartis Investigative Site

Taipei, , Taiwan

Countries

Canada; China; France; Germany; Hong Kong; Italy; South Korea; Taiwan

References

Santoro A, Assenat E, Yau T, Delord JP, Maur M, Knox J, Cattan S, Lee KH, Del Conte G, Springfeld C, Leo E, Xyrafas A, Fairchild L, Mardjuadi F, Chan SL. A phase Ib/II trial of capmatinib plus spartalizumab vs. spartalizumab alone in patients with pretreated hepatocellular carcinoma. JHEP Rep. 2024 Jan 28;6(4):101021. doi: 10.1016/j.jhepr.2024.101021. eCollection 2024 Apr.

Reference Type: DERIVED

PMID: 38617599 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-005417-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CINC280X2108

Identifier Type: -

Identifier Source: org_study_id