- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03655613
APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC
A Phase 1/2 Dose Escalation and Expansion Study of Combination APL-501 or Nivolumab With APL-101 in Locally Advanced or Metastatic Hepatocellular and Renal Cell Carcinoma
Study Design and Investigational Plan:
This is an open-label Phase 1/2 study to assess the safety and tolerability of combination PD-1 inhibitor (APL-501 or nivolumab) administered concomitantly with c-Met inhibitor (APL-101), to determine the recommended Phase 2 dose of the combination, and to obtain preliminary efficacy in HCC or RCC subjects with advanced or metastatic disease that have not been previously treated with a PD 1 inhibitor or a c-Met inhibitor. HCC subjects will receive the combination APL-501 plus APL-101 while RCC subjects will receive the combination nivolumab plus APL-101. In Phase 1, mandatory archival or fresh tumor biopsies will be collected. In Phase 2, a mandatory fresh tumor biopsy will be required for study entry and another fresh biopsy will be collected between Cycles 2 and 4. The frequency of administration of PD-1 inhibitors will be every 2 weeks starting in Cycle 1 on Day 8 and Day 22 of a 35-day cycle with all subsequent cycles on Day 1 and Day 15 of 28-day cycles. APL-101 will be administered orally every 12 hours continuously on an empty stomach.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
New South Wales
-
Albury, New South Wales, Australia, 2640
- Border Medical Oncology Research Unit
-
Sydney, New South Wales, Australia, 2109
- Macquarie University
-
-
New South Whales
-
Westmead, New South Whales, Australia, 2145
- Crown Princess Mary Cancer Centre
-
-
South Australia
-
Adelaide, South Australia, Australia, 5037
- Ashford Cancer Center
-
-
Victoria
-
Melbourne, Victoria, Australia, 3050
- Royal Melbourne Hospital
-
Saint Albans, Victoria, Australia, 3021
- Sunshine Hospital
-
-
Western Australia
-
Murdoch, Western Australia, Australia, 6150
- Fiona Stanley Hospital
-
Perth, Western Australia, Australia, 6018
- Afffinity Clinical Research
-
-
-
-
-
Auckland, New Zealand, 1023
- Auckland City Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent.
- Men and women 18 years of age or older.
- Histologically confirmed advanced or metastatic hepatocellular carcinoma that progressed while receiving at least one previous line of systemic therapy, including sorafenib, or who are intolerant of or refused sorafenib treatment following progression on standard therapy including surgical and/or local regional therapies, or standard therapy considered ineffective, intolerable, or inappropriate or for which no effective standard therapy is available.
- Histologically confirmed advanced or metastatic renal cell carcinoma with clear cell component who received one or two prior lines of antiangiogenic therapy in addition to no more than three previous regimens of systemic therapy including cytokines and cytotoxic chemotherapy agents.
- Disease according to irRECIST that can be reliably and consistently followed.
- Documented disease progression during or after the last treatment regimen and within 6 months before study enrollment.
- Tumor amenable to tumor biopsy and subject agreeable to tumor biopsy at study entry and during therapy with study treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Acceptable organ function.
Exclusion Criteria:
- History of severe hypersensitivity to mAbs, excipients of the APL-501, nivolumab, or APL-101.
- History of receiving treatment with any c-Met signaling pathway inhibitor (marketed or investigational agents).
- Prior therapy with anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-stimulation pathways).
- Unwilling to swallow orally administered medication whole.
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
- Documented and/or known history of human immunodeficiency virus (HIV) for HCC and RCC subjects, or historical seropositive results consistent with active infection for hepatitis C virus (HCV) or hepatitis B virus (HBV) (RCC only).
- HCC subjects receiving active antiviral therapy for HCV.
- Active co-infection with HBV and HCV.
- Active co-infection with HBV and hepatitis D virus.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Arm A: Hepatocellular Carcinoma
PD-1 inhibitor (APL-501) 3 mg/kg intravenously every 2 weeks + c-Met inhibitor (APL-101) 150 mg or 200 mg administered twice daily continuously until documented disease progression, discontinuation due to toxicity withdrawal of consent or the study ends
|
Humanized IgG4 monoclonal antibody against programmed death receptor-1 (PD-1)
Other Names:
Oral specific c-Met inhibitor
Other Names:
|
EXPERIMENTAL: Arm B: Renal Cell Carcinoma
PD-1 inhibitor (nivolumab) 3 mg/kg or 240 mg intravenously every 2 weeks + c-Met inhibitor (APL-101) 300 mg or 400 mg administered twice daily continuously until documented disease progression, discontinuation due to toxicity withdrawal of consent or the study ends
|
Oral specific c-Met inhibitor
Other Names:
Fully human IgG4 monoclonal antibody against PD-1
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose Limiting Toxicities (Phase 1)
Time Frame: Cycle 1 (up to 35 days)
|
Dose limiting toxicities (DLTs)
|
Cycle 1 (up to 35 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse events
Time Frame: First dose up to 90 days post last dose (up to approximately 2 years)
|
Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0.
including immune related adverse events (irAEs)
|
First dose up to 90 days post last dose (up to approximately 2 years)
|
Drug discontinuation due to adverse events
Time Frame: First dose up to 90 days post last dose (up to approximately 2 years)
|
Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0.
including immune related adverse events (irAEs)
|
First dose up to 90 days post last dose (up to approximately 2 years)
|
Overall Response Rate
Time Frame: Duration of study, performed at baseline, then every 8 weeks until objective disease progression (up to approximately 2 years)
|
Tumor response will be assessed by immune related Response Evaluation Criteria in Solid Tumors (irRECIST)
|
Duration of study, performed at baseline, then every 8 weeks until objective disease progression (up to approximately 2 years)
|
Time to Response
Time Frame: Duration of study, first dose to first response (up to approximately 2 years)
|
Time to response is the time from first dose to date of first response (Partial response or Complete response)
|
Duration of study, first dose to first response (up to approximately 2 years)
|
Progression Free Survival
Time Frame: Duration of study, performed at baseline, then every 8 weeks until objective disease progression at 6, 12, 18 and 24 months (up to approximately 2 years)
|
Progression free survival will be collected on all enrolled subjects, defined as the time from first dose to death from any cause or first observed disease progression
|
Duration of study, performed at baseline, then every 8 weeks until objective disease progression at 6, 12, 18 and 24 months (up to approximately 2 years)
|
Overall Survival
Time Frame: Duration of study, performed every 8 weeks from enrollment to death from any cause at 6, 12, 18, 24 months (up to approximately 2 years)
|
Overall survival will be estimated using the Kaplan-Meier method with the follow-up starting at the initiation of therapy until date of death
|
Duration of study, performed every 8 weeks from enrollment to death from any cause at 6, 12, 18, 24 months (up to approximately 2 years)
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Scott Houston, Apollomics (Australia) Pty. Ltd.
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Kidney Neoplasms
- Carcinoma, Renal Cell
- Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
Other Study ID Numbers
- APOLLO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Renal Cell Carcinoma
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Renal Cell Carcinoma | Metastatic Clear Cell Renal Cell Carcinoma | Advanced Clear Cell Renal Cell Carcinoma | Stage III Renal Cell Cancer AJCC v8 | Stage IV Renal Cell Cancer AJCC v8 | Metastatic Sarcomatoid Renal Cell Carcinoma | Advanced Renal Cell Carcinoma | Unresectable Renal Cell... and other conditionsUnited States
-
Australian and New Zealand Urogenital and Prostate...RecruitingRenal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Papillary Renal Cell Carcinoma Type 1 | Papillary Renal Cell Carcinoma Type 2 | Chromophobe Renal Cell Carcinoma | Xp11.2 Translocation-Related Renal Cell CarcinomaAustralia
-
National Cancer Institute (NCI)CompletedClear Cell Renal Cell Carcinoma | Recurrent Renal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Stage IV Renal Cell Cancer | Chromophobe Renal Cell Carcinoma | Papillary Renal Cell CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedClear Cell Renal Cell Carcinoma | Recurrent Renal Cell Carcinoma | Stage IV Renal Cell Cancer | Type 1 Papillary Renal Cell Carcinoma | Type 2 Papillary Renal Cell CarcinomaUnited States, Taiwan, Australia
-
Bradley A. McGregor, MDBristol-Myers Squibb; ExelixisRecruitingRenal Cell Carcinoma | Chromophobe Renal Cell Carcinoma | Papillary Renal Cell Carcinoma | Unclassified Renal Cell Carcinoma | Collecting Duct Renal Cell Carcinoma | Translocation Renal Cell Carcinoma | Unresectable Advanced Renal Cell Carcinoma | Metastatic Ncc Renal Cell CarcinomaUnited States
-
Jonsson Comprehensive Cancer CenterBeiGene; Driven To CureWithdrawnMetastatic Renal Cell Carcinoma | Stage IV Renal Cell Cancer AJCC v8 | Papillary Renal Cell Carcinoma | Collecting Duct Carcinoma | Unresectable Renal Cell Carcinoma | Hereditary Leiomyomatosis and Renal Cell Carcinoma | Clear Cell Papillary Renal Neoplasm | Hereditary Papillary Renal Cell Carcinoma and other conditionsUnited States
-
Memorial Sloan Kettering Cancer CenterActive, not recruitingChromophobe Renal Cell Carcinoma | Papillary Renal Cell Carcinoma | Unclassified Renal Cell Carcinoma | Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma | Fumarate Hydratase Deficient Renal Cell Carcinoma | Succinate Dehydrogenase Deficient Renal Cell Carcinoma | Collecting Duct Renal...United States
-
Australian and New Zealand Urogenital and Prostate...Bristol-Myers SquibbActive, not recruitingRenal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Papillary Renal Cell Carcinoma Type 1 | Papillary Renal Cell Carcinoma Type 2 | Chromophobe Renal Cell Carcinoma | Xp11 Translocation CarcinomaAustralia
-
Peloton Therapeutics, Inc.Active, not recruitingKidney Cancer | Renal Cell Carcinoma | Renal Cancer | Renal Cell Carcinoma (RCC) | Renal Cell Cancer Metastatic | Kidney | Clear Cell Renal Cell Carcinoma (ccRCC) | Renal Cell Carcinoma Recurrent | Renal Cell Cancer, RecurrentUnited States
-
AmgenCompletedRenal Cell Carcinoma | Clear Cell Renal Cell Carcinoma | Clear Cell Renal Carcinoma | Renal Cell AdenocarcinomaFrance, United States, Germany
Clinical Trials on APL-501
-
Apollomics (Australia) Pty. Ltd.Novotech (Australia) Pty Limited; Apollomics Inc. (formerly CBT Pharmaceuticals...CompletedSolid Tumor | Microsatellite Instability | Mismatch Repair Deficiency | Cancer of Unknown Primary SiteAustralia
-
Jiangsu Yahong Meditech Co., Ltd aka AsierisNot yet recruiting
-
Asieris Pharmaceuticals (AUS) Pty Ltd.Completed
-
Apellis Pharmaceuticals, Inc.CompletedNeovascular Age-Related Macular DegenerationUnited States, Australia
-
Jiangsu Yahong Meditech Co., Ltd aka AsierisRecruitingUlcerative ColitisUnited States
-
Apellis Pharmaceuticals, Inc.CompletedGeographic AtrophyUnited States, Australia, New Zealand
-
Apellis Pharmaceuticals, Inc.Terminated
-
Chong Kun Dang PharmaceuticalCompletedType 2 Diabetes MellitusKorea, Republic of
-
Apellis Pharmaceuticals, Inc.Active, not recruitingLupus Nephritis | IgA Nephropathy | Membranous Nephropathy | C3 Glomerulonephritis | Dense Deposit DiseaseUnited States
-
Asieris Pharmaceutical Technologies Co., Ltd.CompletedNon-Muscle Invasive Bladder Cancer (NMIBC)United States