APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC
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|ClinicalTrials.gov Identifier: NCT03655613|
Recruitment Status : Terminated (Study terminated due to administrative reasons.)
First Posted : August 31, 2018
Last Update Posted : May 6, 2022
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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.
|Condition or disease||Intervention/treatment||Phase|
|Hepatocellular Carcinoma Renal Cell Carcinoma||Biological: APL-501 Drug: APL-101 Biological: Nivolumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||(Phase 1) 3+3 dose escalation (Phase 2) Simon two-stage Minimax design|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||September 5, 2018|
|Actual Primary Completion Date :||December 15, 2021|
|Actual Study Completion Date :||December 15, 2021|
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)
Oral specific c-Met inhibitor
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
Fully human IgG4 monoclonal antibody against PD-1
Other Name: Opdivo
- Dose Limiting Toxicities (Phase 1) [ Time Frame: Cycle 1 (up to 35 days) ]Dose limiting toxicities (DLTs)
- 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)
- 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)
- 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)
- 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)
- 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
- 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
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03655613
|Australia, New South Wales|
|Border Medical Oncology Research Unit|
|Albury, New South Wales, Australia, 2640|
|Sydney, New South Wales, Australia, 2109|
|Australia, New South Whales|
|Crown Princess Mary Cancer Centre|
|Westmead, New South Whales, Australia, 2145|
|Australia, South Australia|
|Ashford Cancer Center|
|Adelaide, South Australia, Australia, 5037|
|Royal Melbourne Hospital|
|Melbourne, Victoria, Australia, 3050|
|Saint Albans, Victoria, Australia, 3021|
|Australia, Western Australia|
|Fiona Stanley Hospital|
|Murdoch, Western Australia, Australia, 6150|
|Afffinity Clinical Research|
|Perth, Western Australia, Australia, 6018|
|Auckland City Hospital|
|Auckland, New Zealand, 1023|
|Study Director:||Scott Houston||Apollomics (Australia) Pty. Ltd.|
|Responsible Party:||Apollomics (Australia) Pty. Ltd.|
|Other Study ID Numbers:||
|First Posted:||August 31, 2018 Key Record Dates|
|Last Update Posted:||May 6, 2022|
|Last Verified:||May 2022|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action