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Hepatocellular CarcinomaPhase 1/2NCT03655613

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

A Phase 1/2 study testing APL-501, APL-101 and Nivolumab in people with Hepatocellular Carcinoma and Renal Cell Carcinoma, run by Apollomics (Australia) Pty. Ltd. at 9 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
APL-501, APL-101 and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
9 sitesin 2 countries
Study dates
5 Sep 2018to 15 Dec 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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).
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  • HCC subjects receiving active antiviral therapy for HCV.
  • Active co-infection with HBV and HCV.
  • Active co-infection with HBV and hepatitis D virus.

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

Australia8 sites

  • Ashford Cancer Center

    Adelaide, South Australia, 5037

  • Border Medical Oncology Research Unit

    Albury, New South Wales, 2640

  • Royal Melbourne Hospital

    Melbourne, Victoria, 3050

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6150

  • Afffinity Clinical Research

    Perth, Western Australia, 6018

  • Sunshine Hospital

    Saint Albans, Victoria, 3021

  • Macquarie University

    Sydney, New South Wales, 2109

  • Crown Princess Mary Cancer Centre

    Westmead, New South Whales, 2145

Other trials in Australia

New Zealand1 site

  • Auckland City Hospital

    Auckland, 1023

Other trials in New Zealand

About this study

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 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.

Read the 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

Being tested
APL-501, APL-101, Nivolumab
Keywords
Immunotherapy, PD-1 inhibitor, c-Met inhibitor
Medical subject headings
Carcinoma, Hepatocellular, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APL-501Biological

    Also called genolimzumab, GB226, CBT-501

    Humanized IgG4 monoclonal antibody against programmed death receptor-1 (PD-1)

  • APL-101Drug

    Also called bozitinib, vebreltinib, CBT-501

    Oral specific c-Met inhibitor

  • NivolumabBiological

    Also called Opdivo

    Fully human IgG4 monoclonal antibody against PD-1

Study groups in NCT03655613
Study groupRoleWhat they receive
Arm A: Hepatocellular CarcinomaExperimentalPD-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
Receives: Biological: APL-501; Drug: APL-101
Arm B: Renal Cell CarcinomaExperimentalPD-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
Receives: Drug: APL-101; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicities (Phase 1)

    Dose limiting toxicities (DLTs)

    Measured: Cycle 1 (up to 35 days)

Secondary outcomes (6)

  1. Adverse events

    Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0. including immune related adverse events (irAEs)

    Measured: First dose up to 90 days post last dose (up to approximately 2 years)

  2. 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)

    Measured: First dose up to 90 days post last dose (up to approximately 2 years)

  3. Overall Response Rate

    Tumor response will be assessed by immune related Response Evaluation Criteria in Solid Tumors (irRECIST)

    Measured: Duration of study, performed at baseline, then every 8 weeks until objective disease progression (up to approximately 2 years)

  4. Time to Response

    Time to response is the time from first dose to date of first response (Partial response or Complete response)

    Measured: Duration of study, first dose to first response (up to approximately 2 years)

  5. 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

    Measured: 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)

  6. 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

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2018
  2. Study start5 Sep 2018
  3. Primary completion15 Dec 2021
  4. Study completion15 Dec 2021

Why it stopped: Study terminated due to administrative reasons.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
(Phase 1) 3+3 dose escalation (Phase 2) Simon two-stage Minimax design
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03655613
Sponsor's protocol ID
APOLLO
Status last verified
May 2022
First submitted
17 Jul 2018
Last updated
6 May 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing APL-501, APL-101 and Nivolumab in people with Hepatocellular Carcinoma and Renal Cell Carcinoma, run by Apollomics (Australia) Pty. Ltd. at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study terminated due to administrative reasons.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicities (Phase 1) (time frame: Cycle 1 (up to 35 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03655613.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2022.

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