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

NCT02795429 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CINC280X21082015-005417-76
• Study Type: interventional
• Target: 89
• Locations: 8 countries
• Sites: 17

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).

Conditions

Advanced Hepatocellular Carcinoma

Keywords

Phase Ib/II; INC280; PDR001; capmatinib; spartalizumab; checkpoint inhibitor; PD-1; Liver cancer

Outcome Measures

Primary Outcomes (6)

• Phase Ib: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period

  Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. For CTCAE v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.

  From first dose of study medication up to 30 days after last dose, with a maximum duration of 3.3 years

• Phase Ib: Number of Participants With Dose-Limiting Toxicities (DLTs) During the First 2 Cycles of Treatment

  A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications that occurs within the first 2 cycles of treatment with capmatinib in combination with spartalizumab during the dose escalation part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher. The duration of one treatment cycle is 21 days.

  42 days

• Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of Capmatinib and Spartalizumab

  Number of participants with at least one dose reduction of capmatinib and spartalizumab and number of participants with at least one dose interruption of capmatinib and spartalizumab. No dose modifications (i.e. dose reduction) were allowed for spartalizumab.

  From first dose of study medication up to last dose, with a maximum duration of 3.2 years

• Phase Ib: Dose Intensity of Capmatinib

  Dose intensity of capmatinib was calculated as actual cumulative dose in milligrams divided by duration of exposure in days.

  From first dose of study medication up to last dose, with a maximum duration of 3.2 years

• Phase Ib: Dose Intensity of Spartalizumab

  Dose intensity of spartalizumab was calculated as actual cumulative dose in milligrams divided by duration of exposure in weeks and then multiplied by 3 weeks (3W).

  From first dose of study medication up to last dose, with a maximum duration of 3.2 years

• Phase II: Overall Response Rate (ORR) Per RECIST v1.1

  Tumor response was based on local investigator assessment as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. ORR per RECIST v1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  From start of treatment until end of treatment, assessed up to 2.2 years

Secondary Outcomes (26)

• Phase Ib and Phase II: Best Overall Response (BOR) Per RECIST v1.1

  From start of treatment until end of treatment, assessed up to 3.2 years in Phase Ib and up to 2.2 years in Phase II

• Phase Ib and Phase II: Best Overall Response (BOR) Per irRC

  From start of treatment until end of treatment, assessed up to 3.2 years in Phase Ib and up to 2.2 years in Phase II

• Phase Ib: Overall Response Rate (ORR) Per RECIST v1.1

  From start of treatment until end of treatment, assessed up to 3.2 years

• Phase Ib and Phase II: Overall Response Rate (ORR) Per irRC

  From start of treatment until end of treatment, assessed up to 3.2 years in Phase Ib and up to 2.2 years in Phase II

• Phase Ib and Phase II: Duration of Response (DOR) Per RECIST v1.1

  From first documented response to first documented disease progression or death due to any cause, assessed up to 3.2 years in Phase Ib and up to 2.2 years in Phase II

Study Arms (5)

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

EXPERIMENTAL

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

Drug: Spartalizumab; Drug: Capmatinib

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

EXPERIMENTAL

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

Drug: Spartalizumab; Drug: Capmatinib

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

EXPERIMENTAL

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

Drug: Spartalizumab; Drug: Capmatinib

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

EXPERIMENTAL

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

Drug: Spartalizumab; Drug: Capmatinib

Phase II: Spartalizumab 300 mg Q3W

EXPERIMENTAL

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

Drug: Spartalizumab

Interventions

Spartalizumab DRUG

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

Also known as: PDR001

Phase II: Capmatinib 400 mg BID + Spartalizumab 300 mg Q3W; Phase II: Spartalizumab 300 mg Q3W; Phase Ib: Capmatinib 200 mg BID + Spartalizumab 300 mg Q3W; Phase Ib: Capmatinib 300 mg BID + Spartalizumab 300 mg Q3W; Phase Ib: Capmatinib 400 mg BID + Spartalizumab 300 mg Q3W

Capmatinib DRUG

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

Also known as: INC280

Phase II: Capmatinib 400 mg BID + Spartalizumab 300 mg Q3W; Phase Ib: Capmatinib 200 mg BID + Spartalizumab 300 mg Q3W; Phase Ib: Capmatinib 300 mg BID + Spartalizumab 300 mg Q3W; Phase Ib: Capmatinib 400 mg BID + Spartalizumab 300 mg Q3W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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),.
• ECOG Performance Status ≤ 1.
• Willing and able to swallow and retain oral medication.

You may not qualify if:

• Use of any live vaccines within 4 weeks of initiation of study treatment.
• History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
• Clinically significant pleural effusion that either required pleurocentesis or is associated with shortness of breath.
• Active autoimmune disease or a documented history of autoimmune disease.
• Clinically significant, uncontrolled heart diseases.
• 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.)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (17)

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510515, China

Location

Novartis Investigative Site

Shanghai, Shanghai Municipality, 200032, China

Location

Novartis Investigative Site

Montpellier, Herault, 34059, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Modena, MO, 41124, Italy

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Tainan, 70403, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 38617599 DERIVED

MeSH Terms

Conditions

Liver Neoplasms

Interventions

spartalizumab; capmatinib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2016
• First Posted: June 10, 2016
• Study Start: June 15, 2016
• Primary Completion: June 1, 2021
• Study Completion: June 24, 2021
• Last Updated: July 3, 2023
• Results First Posted: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share

Locations

FR (3); TW (2); CN (2); DE (2); CA (2); HK (1); IT (3); KR (2)