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

• Status: Active, not recruiting
• Trial end date: 2021-12-15
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Apollomics (Australia) Pty. Ltd.; CBT Pharmaceuticals (Australia) Pty Ltd
• Collaborators: Apollomics Inc. (formerly CBT Pharmaceuticals, Inc.); CBT Pharmaceuticals, Inc.; Novotech (Australia) Pty Limited
• Treatments: Antibodies, Monoclonal; Nivolumab

Criteria

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.