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APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC

Primary Purpose

Hepatocellular Carcinoma, Renal Cell Carcinoma

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
APL-501
APL-101
Nivolumab
Sponsored by
Apollomics (Australia) Pty. Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Immunotherapy, PD-1 inhibitor, c-Met inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent.
  2. Men and women 18 years of age or older.
  3. 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.
  4. 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.
  5. Disease according to irRECIST that can be reliably and consistently followed.
  6. Documented disease progression during or after the last treatment regimen and within 6 months before study enrollment.
  7. Tumor amenable to tumor biopsy and subject agreeable to tumor biopsy at study entry and during therapy with study treatment.
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  9. Acceptable organ function.

Exclusion Criteria:

  1. History of severe hypersensitivity to mAbs, excipients of the APL-501, nivolumab, or APL-101.
  2. History of receiving treatment with any c-Met signaling pathway inhibitor (marketed or investigational agents).
  3. 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).
  4. Unwilling to swallow orally administered medication whole.
  5. 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).
  6. 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).
  7. HCC subjects receiving active antiviral therapy for HCV.
  8. Active co-infection with HBV and HCV.
  9. Active co-infection with HBV and hepatitis D virus.

Sites / Locations

  • Border Medical Oncology Research Unit
  • Macquarie University
  • Crown Princess Mary Cancer Centre
  • Ashford Cancer Center
  • Royal Melbourne Hospital
  • Sunshine Hospital
  • Fiona Stanley Hospital
  • Afffinity Clinical Research
  • Auckland City Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A: Hepatocellular Carcinoma

Arm B: Renal Cell Carcinoma

Arm Description

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

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

Outcomes

Primary Outcome Measures

Dose Limiting Toxicities (Phase 1)
Dose limiting toxicities (DLTs)

Secondary Outcome Measures

Adverse events
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
Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0. including immune related adverse events (irAEs)
Overall Response Rate
Tumor response will be assessed by immune related Response Evaluation Criteria in Solid Tumors (irRECIST)
Time to Response
Time to response is the time from first dose to date of first response (Partial response or Complete response)
Progression Free Survival
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
Overall survival will be estimated using the Kaplan-Meier method with the follow-up starting at the initiation of therapy until date of death

Full Information

First Posted
July 17, 2018
Last Updated
May 3, 2022
Sponsor
Apollomics (Australia) Pty. Ltd.
Collaborators
Apollomics Inc. (formerly CBT Pharmaceuticals, Inc.), Novotech (Australia) Pty Limited
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1. Study Identification

Unique Protocol Identification Number
NCT03655613
Brief Title
APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
Study terminated due to administrative reasons.
Study Start Date
September 5, 2018 (Actual)
Primary Completion Date
December 15, 2021 (Actual)
Study Completion Date
December 15, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Apollomics (Australia) Pty. Ltd.
Collaborators
Apollomics Inc. (formerly CBT Pharmaceuticals, Inc.), Novotech (Australia) Pty Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
For each potential subject, there is a 28-day screening and eligibility assessment period before enrollment; the first dose of study treatment will be administered on Day 1 of Cycle 1 (C1D1) (Safety population). Subjects will continue to receive their assigned treatment throughout the study until the occurrence of confirmed disease progression [progressive disease (PD)] by irRECIST, death, unacceptable treatment-related toxicity, or until the study is closed by the Sponsor. During the treatment period, study visits will occur on Day 1, Day 2, Day 8, Day 15, Day 22 of Cycle 1 and Day 1 and Day 15 of every subsequent cycle. Subjects who experience a response [Complete Response (CR), Partial Response (PR)] ≥ 2 cycles, PD 1 plus APL-101 combination will be continued until disease progression based on irRECIST. Subjects should receive a minimal of 2 cycles of PD-1 and APL-101 for adequate evaluation of response (Evaluable population). Discontinuation of PD-1 and APL-101 should occur upon determination of disease progression as determined by irRECIST, intolerable toxicity or when the risk/benefit ratio is no longer beneficial for the subjects as determined by the Principal Investigator, or upon subject withdrawal of consent. Upon permanent discontinuation of study treatment, there is a Treatment Termination visit and three monthly follow-up visits for a 90-day safety follow-up visit period. Subjects who drop out before they complete the first cycle of combination treatment for reasons other than toxicity will be replaced

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Renal Cell Carcinoma
Keywords
Immunotherapy, PD-1 inhibitor, c-Met inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
(Phase 1) 3+3 dose escalation (Phase 2) Simon two-stage Minimax design
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Hepatocellular Carcinoma
Arm Type
Experimental
Arm Description
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
Arm Title
Arm B: Renal Cell Carcinoma
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
APL-501
Other Intervention Name(s)
genolimzumab, GB226, CBT-501
Intervention Description
Humanized IgG4 monoclonal antibody against programmed death receptor-1 (PD-1)
Intervention Type
Drug
Intervention Name(s)
APL-101
Other Intervention Name(s)
bozitinib, vebreltinib, CBT-501
Intervention Description
Oral specific c-Met inhibitor
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo
Intervention Description
Fully human IgG4 monoclonal antibody against PD-1
Primary Outcome Measure Information:
Title
Dose Limiting Toxicities (Phase 1)
Description
Dose limiting toxicities (DLTs)
Time Frame
Cycle 1 (up to 35 days)
Secondary Outcome Measure Information:
Title
Adverse events
Description
Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0. including immune related adverse events (irAEs)
Time Frame
First dose up to 90 days post last dose (up to approximately 2 years)
Title
Drug discontinuation due to adverse events
Description
Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0. including immune related adverse events (irAEs)
Time Frame
First dose up to 90 days post last dose (up to approximately 2 years)
Title
Overall Response Rate
Description
Tumor response will be assessed by immune related Response Evaluation Criteria in Solid Tumors (irRECIST)
Time Frame
Duration of study, performed at baseline, then every 8 weeks until objective disease progression (up to approximately 2 years)
Title
Time to Response
Description
Time to response is the time from first dose to date of first response (Partial response or Complete response)
Time Frame
Duration of study, first dose to first response (up to approximately 2 years)
Title
Progression Free Survival
Description
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
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)
Title
Overall Survival
Description
Overall survival will be estimated using the Kaplan-Meier method with the follow-up starting at the initiation of therapy until date of death
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Houston
Organizational Affiliation
Apollomics (Australia) Pty. Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Border Medical Oncology Research Unit
City
Albury
State/Province
New South Wales
ZIP/Postal Code
2640
Country
Australia
Facility Name
Macquarie University
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2109
Country
Australia
Facility Name
Crown Princess Mary Cancer Centre
City
Westmead
State/Province
New South Whales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Ashford Cancer Center
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5037
Country
Australia
Facility Name
Royal Melbourne Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Sunshine Hospital
City
Saint Albans
State/Province
Victoria
ZIP/Postal Code
3021
Country
Australia
Facility Name
Fiona Stanley Hospital
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6150
Country
Australia
Facility Name
Afffinity Clinical Research
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6018
Country
Australia
Facility Name
Auckland City Hospital
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand

12. IPD Sharing Statement

Links:
URL
http://www.apollomicsinc.com/
Description
Company website for Apollomics Inc.

Learn more about this trial

APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC

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