Oncology Investigational Drug Developments Remain Promising, Despite Impact of COVID-19 Pandemic on Clinical Trials

With a myriad of investigational oncology drugs in development, the COVID-19 pandemic has led investigators to reconsider how clinical trials are currently conducted, according to a presentation at the Hematology/Oncology Pharmacy Association (HOPA) virtual 2021 conference.

Presenter Heidi D. Finnes, PharmD, BCOP, FHOPA, president-elect of HOPA, explored some promising investigational oral taxanes, small molecule drugs, and immunotherapies. Although many of these drugs are new, Finnes said older drugs can also have new delivery routes to investigate.

Oral paclitaxel is one such drug, which is able to be absorbed into the bloodstream when given with a P-glucoprotein inhibitor that is minimally absorbed, Finnes said. Clinical trials of oral paclitaxel plus encequidar have found higher rates of overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) with associated toxicities of gastrointestinal adverse events (AEs) and increased risk of neutropenia. Pharmacists can play an important role preparing patients for gastrointestinal AEs, advising them to stay well hydrated.

“One of the great things about giving paclitaxel orally is there is decreased neuropathy with oral paclitaxel and encequidar,” Finnes said in the presentation.

Despite these encouraging findings, a recent update by the FDA cited concerns about high rates of neutropenia with the oral combination compared to intravenous paclitaxel. The officials recommended a new “adequate and well-conducted” trial, although the FDA has granted priority review for the combination based on the KX-ORAX-001 trial results.

Finnes said oral options are convenient for many patients, although the high pill burden may negatively impact quality of life. For example, she said oral paclitaxel requires 10 to 11 pills per day with various fasting times, so this burden is important to consider.

Small molecule drugs are also under investigation, including wee1 and AKT inhibitors. Wee1 is a protein kinase, which can allow for continued cell cycle progression when inhibited, while still harboring unrepaired damage to DNA. Finnes said this inability to repair DNA results in cancer cell death. Adavosertib is a wee1 inhibitor that has been investigated in uterine serous carcinoma.

In the clinical trial, adavosertib was administered 300 mg once daily on days 1 through 5 and 8 through 12 of a 21-day cycle. Investigators found an ORR of 29.4% and a PFS of 47% at 6 months, which Finnes said are “significant findings.” Common toxicities included neutropenia, anemia, and fatigue.

AKT inhibitors can halt signaling to the tumor nucleus and prevent tumor genesis, Finnes said. Most ongoing clinical trials are investigating these drugs in breast cancers, although a few are looking at ovarian and lung cancers.

In the IPATunity130 trial of ipatasertib plus paclitaxel, Finnes said researchers found no significant difference in PFS compared to paclitaxel plus a placebo, although there may be more potential in subgroups for which PIK3CA, AKT, and PTEN alterations derive some benefit from ipatasertib.

Next, Finnes turned to investigational immunotherapies, including T cell immunoglobulin and ITIM domain (TIGIT) inhibitors, and B-cell maturation agent (BCMA)-targeted therapies. TIGIT has emerged as a key target for anti-tumor response, Finnes said, with multiple mechanisms of action in which it may work and several ongoing clinical trials.

A clinical trial of the TIGIT inhibitor tiragolumab plus atezolizumab found a 31.3% ORR in the tiragolumab treatment group, compared to a 16.2% rate in the atezolumab plus placebo group. Similarly, researchers found a median PFS of 5.4 months in the tiragolumab treatment group compared to 3.6 months. Notably, all toxicities did not appear any different when looking at the combination compared to atezolizumab alone, and the treatment was fairly well tolerated.

BCMA-targeted chimeric antigen receptor T-cell therapies are also showing promise, with clinical trials of idecabtagene and orvacabtagene showing encouraging response rates. The clinical trial of idecabtagene showed a 76% ORR and a 39% complete response rate (CRR), while the orvacabtagene trial found a 91% ORR and a 39% CRR. Both of these are extremely encouraging, Finnes said, noting that clinicians must closely monitor for cytokine release syndrome and neurotoxicity.

Finally, Finnes discussed some ways in which clinical trials have changed during the COVID-19 pandemic, and whether these changes will continue into the future. Before the pandemic, many patients would travel long distances to visit a treatment facility, see many health care providers, and conduct scans and treatments, all to even establish whether they were a candidate. Surveys since the pandemic began, however, have found that patients and providers alike are satisfied with virtual visits and procedures.

According to a survey by the American Society of Clinical Oncology, challenges in clinical trial conducted during the COVID-19 pandemic included patients’ decreased ability or willingness to visit the facility (56%), limited ancillary services (52%), and time with sponsors spent modifying the procedures (52%).

Many respondents also said that more telehealth options should continue in the future, including telehealth visits, which more than 90% of respondents said they support. Similarly, survey respondents said remote review of symptoms, remote site initiation visits, remote monitoring, and remote lab collection should all be more permitted in future oncology clinical trials.

REFERENCE

Finnes, H. Oncology Investigational Drug Development: What’s New in Our Armamentarium and How Has Clinical Trial Conduct Changed Post-COVID-19? Presented at: Hematology/Oncology Pharmacy Association virtual 2021 conference; April 14, 2021. Accessed April 14, 2021.