Phase 2
Completed N=89
Phase Ib/II Study of INC280 + PDR001 or PDR001 Single Agent in Advanced HCC
Source: ClinicalTrials.gov NCT02795429 ↗Enrolled (actual)
89
Serious AEs
38.2%
Results posted
Jul 2023
Primary outcomePrimary: Phase Ib: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period — 6; 10; 10; 5 Participants
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase Ib: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period |
6; 10; 10; 5; 7; 10 | — |
| PRIMARY Phase Ib: Number of Participants With Dose-Limiting Toxicities (DLTs) During the First 2 Cycles of Treatment |
0; 0; 1 | — |
| PRIMARY Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of Capmatinib and Spartalizumab |
2; 4; 8; 4; 6; 8 | — |
| PRIMARY Phase Ib: Dose Intensity of Capmatinib |
391.2; 580.0; 755.6 | — |
| PRIMARY Phase Ib: Dose Intensity of Spartalizumab |
293.18; 300.00; 300.00 | — |
| PRIMARY Phase II: Overall Response Rate (ORR) Per RECIST v1.1 |
9.4; 10.0 | — |
| SECONDARY Phase Ib and Phase II: Best Overall Response (BOR) Per RECIST v1.1 |
0; 0; 0; 0; 0; 2 | — |
| SECONDARY Phase Ib and Phase II: Best Overall Response (BOR) Per irRC |
0; 0; 0; 0; 0; 2 | — |
| SECONDARY Phase Ib: Overall Response Rate (ORR) Per RECIST v1.1 |
33.3; 0; 18.2 | — |
| SECONDARY Phase Ib and Phase II: Overall Response Rate (ORR) Per irRC |
33.3; 0; 27.3; 12.5; 10.0 | — |
| SECONDARY Phase Ib and Phase II: Duration of Response (DOR) Per RECIST v1.1 |
NA; NA; NA; NA | — |
| SECONDARY Phase Ib and Phase II: Duration of Response (DOR) Per irRC |
NA; NA; NA; NA | — |
| SECONDARY Phase Ib and Phase II: Time to Response (TTR) Per RECIST v1.1 |
NA; NA; NA; NA; NA | — |
| SECONDARY Phase Ib and Phase II: Time to Response (TTR) Per irRC |
NA; NA; NA; NA; NA | — |
| SECONDARY Phase Ib and Phase II: Progression-Free Survival (PFS) Per RECIST v1.1 |
3.42; 4.44; 1.35; 2.79; 2.79 | — |
| SECONDARY Phase Ib and Phase II: Progression-Free Survival (PFS) Per irRC |
3.42; 4.44; 5.55; 3.06; 2.79 | — |
| SECONDARY Phase Ib and Phase II: Time to Progression (TTP) Per RECIST v1.1 |
3.42; 4.44; 1.35; 2.79; 2.79 | — |
| SECONDARY Phase Ib and Phase II: Time to Progression (TTP) Per irRC |
3.42; 4.44; 5.55; 3.06; 2.79 | — |
| SECONDARY Phase Ib and Phase II: Overall Survival (OS) |
14.98; 12.11; 16.53; 14.88; 9.78 | — |
| SECONDARY Phase II: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period |
32; 30; 30; 18; 25; 15 | — |
| SECONDARY Phase II: Number of Participants With Dose Reductions and Dose Interruptions of Capmatinib and Spartalizumab |
18; 22; 0; 0; 12; 13 | — |
| SECONDARY Phase II: Dose Intensity of Capmatinib |
696.4 | — |
| SECONDARY Phase II: Dose Intensity of Spartalizumab |
300.00; 300.00 | — |
| SECONDARY Phase Ib: Maximum Observed Plasma Concentration (Cmax) of Capmatinib |
1680; 3110; 4980 | — |
| SECONDARY Phase Ib: Time to Reach Maximum Plasma Concentration (Tmax) of Capmatinib |
0.959; 1.00; 1.00 | — |
| SECONDARY Phase Ib: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Capmatinib |
5740; 8570; 16000 | — |
| SECONDARY Phase II: Pre-dose Plasma Concentration of Capmatinib |
607; 345; 410; 363; 275 | — |
| SECONDARY Phase Ib and Phase II: Maximum Observed Serum Concentration (Cmax) of Spartalizumab |
75.7; 77.2; 84.7; 81.7; 72.8; 105 | — |
| SECONDARY Phase Ib and Phase II: Time to Reach Maximum Serum Concentration (Tmax) of Spartalizumab |
1.51; 1.50; 1.50; 1.64; 1.59; 1.53 | — |
| SECONDARY Phase Ib and Phase II: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Spartalizumab |
739; 726; 813; 805; 693; 1280 | — |
| SECONDARY Phase Ib and Phase II: Percent Marker Area for CD8 Expression in Tumor Samples |
0.6; 0.9; 0.4; 0.5; 0.3; 3.0 | — |
| SECONDARY Phase Ib and Phase II: PD-L1 Percent Positive Tumor |
0.0; 0.0; 0.0; 0.0; 0.0; 12.5 | — |
Eligibility Criteria
Inclusion Criteria
- 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.
Exclusion Criteria
- 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) 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)
Data sourced from ClinicalTrials.gov (NCT02795429). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.