CBT Pharmaceuticals has dosed the first participant in its Phase 1/2 clinical trial assessing the safety and tolerability of CBT-101, in combination with PD-1 inhibitors, in advanced or metastatic hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC).
In adults, HCC is the most common type of primary liver cancer, and RCC is the most common type of primary kidney cancer.
This marks the beginning of the APOLLO series of oncology clinical trials program. The plan will be carried out by CBT to evaluate if CBT-101 works in combination with other molecular agents to improve single agent immunotherapy response rates, and subsequently contributes to cancer treatment.
“Initiating our APOLLO Oncology Clinical Trials Program and dosing the first patient is a major milestone for CBT as we advance our mission to improve the lives of cancer patients through combination treatment regimens,” Sanjeev Redkar, PhD, co-founder, president and CEO of CBT Pharmaceuticals, said in a press release.
“The APOLLO program is designed to investigate our proprietary assets alongside each other and is focused on understanding the science and genetics to identify the appropriate patients likely to benefit from the regimen. We are grateful for the support of our investigators in running our series of trials,” Redkar said.
The open-label, non-randomized, multicenter, dose-escalation study (NCT03655613) is recruiting participants, and researchers estimate they will enroll 119 subjects. Trial locations include Afffinity Clinical Research in Perth, Australia, and Auckland City Hospital in New Zealand.
CBT-101 (bozitinib) is an oral c-Met inhibitor that, as its name implies, suppresses the activity of the c-Met signaling pathway, which is overly activated in many types of cancer, including kidney and lung cancers. In addition, this molecular pathway plays a key role in the disease mechanism of cancer, like tumor growth, survival, and metastasis.
In this Phase 1/2 trial, researchers will assess the safety and tolerability of their c-Met inhibitor CBT-101 in combination with a PD-1 inhibitor — CBT-501, also known as genolimzumab, for HCC patients, or Opdivo (nivolumab) for those with RCC.
The trial will help determine the recommended Phase 2 dose of the combination. It also will provide preliminary efficacy data in HCC or RCC subjects with advanced or metastatic disease who have not been previously treated with a PD-1 inhibitor or a c-Met inhibitor.
PD-1, found on T-cells, helps control the body’s immune responses. When PD-1 is bound to another protein, called PD-L1, at the surface of cancer cells, T-cells no longer are able to recognize and eliminate the abnormal cells.
By blocking PD-1 (i.e., not giving the chance for PD-L1 to bind to PD-1) the body’s natural immune response is not blocked, and T-cells can destroy cancer cells.
Almost three years ago, Opdivo, one of the PD-1 inhibitors used in this trial, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic renal cell carcinoma.
Patients will receive a minimum of two cycles of PD-1 and CBT-101 for adequate evaluation of response. PD-1 inhibitors will be given intravenously every two weeks and CBT-101 will be taken orally, every 12 hours.
Patients will be evaluated on days 1, 2, 8, 15, and 22 of cycle 1, and once every two weeks thereafter.
Apart from trial termination, treatment protocol will stop in case of documented disease progression or patient’s discontinuation due to too much toxicity. Upon permanent discontinuation of study treatment, there will be a three-month follow-up period in which patients will be assessed every 30 days.
For the Phase 1 part of this trial, primary outcomes include identification of any dose-limiting toxicities, evaluation of overall safety, and assessment of CBT-101 plus CBT-501 for HCC, and CBT-101 plus Opdivo for RCC.
Phase 2’s primary goal is to assess preliminary effectiveness by measuring objective response rate and duration of response. Secondary objectives include determining the recommended Phase 2 dose, ascertaining the biological fate of CBT-101 and CBT-501 when administered together, plus assessing clinical benefit rate, time to disease progression or death, and overall survival.
“One of the newer paradigms for treating cancer patients is combining immunotherapy agents as this synergistic approach may provide improved outcomes. In this first trial in the series, we believe that giving a c-Met inhibitor concomitantly with an anti PD-1 therapy may produce a positive added response in patients with HCC and RCC where monotherapy treatment has proven effective,” said Alex Powell, Affinity Oncology, Hollywood Private Hospital in Perth, Western Australia.