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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03655613




Registration number
NCT03655613
Ethics application status
Date submitted
17/07/2018
Date registered
31/08/2018
Date last updated
6/06/2019

Titles & IDs
Public title
APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC
Scientific 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
Secondary ID [1] 0 0
APOLLO
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma 0 0
Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - APL-501
Treatment: Drugs - APL-101
Other interventions - Nivolumab

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

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


Other interventions: APL-501
Humanized IgG4 monoclonal antibody against programmed death receptor-1 (PD-1)

Treatment: Drugs: APL-101
Oral specific c-Met inhibitor

Other interventions: Nivolumab
Fully human IgG4 monoclonal antibody against PD-1

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Limiting Toxicities (Phase 1) - Dose limiting toxicities (DLTs)
Timepoint [1] 0 0
Cycle 1 (up to 35 days)
Secondary outcome [1] 0 0
Adverse events - Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0. including immune related adverse events (irAEs)
Timepoint [1] 0 0
First dose up to 90 days post last dose (up to approximately 2 years)
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
First dose up to 90 days post last dose (up to approximately 2 years)
Secondary outcome [3] 0 0
Overall Response Rate - Tumor response will be assessed by immune related Response Evaluation Criteria in Solid Tumors (irRECIST)
Timepoint [3] 0 0
Duration of study, performed at baseline, then every 8 weeks until objective disease progression (up to approximately 2 years)
Secondary outcome [4] 0 0
Time to Response - Time to response is the time from first dose to date of first response (Partial response or Complete response)
Timepoint [4] 0 0
Duration of study, first dose to first response (up to approximately 2 years)
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
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)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,New South WhalesSA,VIC,WA
Recruitment hospital [1] 0 0
Macquarie University - Sydney
Recruitment hospital [2] 0 0
Crown Princess Mary Cancer Centre - Westmead
Recruitment hospital [3] 0 0
Ashford Cancer Center - Adelaide
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [5] 0 0
Sunshine Hospital - Saint Albans
Recruitment hospital [6] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [7] 0 0
Afffinity Clinical Research - Perth
Recruitment postcode(s) [1] 0 0
2109 - Sydney
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
5037 - Adelaide
Recruitment postcode(s) [4] 0 0
3050 - Melbourne
Recruitment postcode(s) [5] 0 0
3021 - Saint Albans
Recruitment postcode(s) [6] 0 0
6150 - Murdoch
Recruitment postcode(s) [7] 0 0
6018 - Perth
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Apollomics (Australia) Pty. Ltd.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Apollomics Inc. (formerly CBT Pharmaceuticals, Inc.)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Novotech (Australia) Pty Limited
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03655613
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Fabio Benedetti, MD
Address 0 0
Apollomics (Australia) Pty. Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Shelly Nigam, MS
Address 0 0
Country 0 0
Phone 0 0
925.272.4090
Fax 0 0
Email 0 0
shelly.nigam@apollomicsinc.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03655613