Several clinical trials in colorectal cancer (CRC) have started recruiting recently. Could one of your patients benefit from participating?
Previously treated metastatic CRC. Adult patients with this type of cancer may be eligible for a National Cancer Institute open-label phase 1/2 study testing a novel vaccine-based regimen that targets a protein on the surface of CRC cells and recruits the immune system to fight the tumor.
For up to 2 years, all study participants will receive intravenous (IV) retifanlimab (Zynyz) and an injection of N-803 (Anktiva) every 4 weeks. They will also receive TriAdeno vaccine injections every 4 weeks for three cycles and then every 12 weeks. A subset of people will also take daily tablets of SX-682, an enhancer of T-cell activation and antitumor immunity, for 3 out of 4 weeks.
The National Institutes of Health Clinical Center in Bethesda, Maryland, started recruiting 60 participants in March 2024. Safety is the primary outcome in the phase 1 study, and overall response rate (ORR) is the primary outcome in the phase 2 study. Overall survival over 2 years is a secondary endpoint, and quality of life (QoL) is not being measured. More details at clinicaltrials.gov
When asked for comment on this trial, Richard Goldberg, MD, professor emeritus at West Virginia University Cancer Institute, Morgantown, West Virginia, said this "first-in-man" study represents "a completely different approach than chemotherapy or other targeted therapies but is in the earliest staging of testing, so the data that support the approach comes from preclinical studies." Goldberg also cautioned that "the treatment program is quite intensive with injections and IV infusions required on a weekly basis and is only available in one site."
Unresectable, locally advanced, or metastatic CRC with an AXIN1 or APC mutation. A phase 2 clinical trial is seeking adults aged 55 years and older who have tried standard therapy without success or are ineligible to test REC-4881. This experimental oral drug targets two common mutations in CRC: AXIN1 and APC. AXIN proteins control pro-oncogenic signaling, and APC proteins are involved in numerous pro-oncogenic processes including cell migration and invasion.
During the trial, participants will take oral capsules of REC-4881 daily for up to 2 years. The trial opened in January 2024 across 28 states looking for 60 participants with a range of solid tumors. Safety, tolerability, and objective response rate are the primary outcomes. Overall survival and QoL are not tracked. More details at clinicaltrials.gov
Goldberg said that REC-4881 has undergone phase 1 studies, so this trial will provide information about its likely activity. "It represents a good possible option for patients who meet the eligibility criteria," Goldberg added.
Unresectable, locally advanced, or metastatic colon cancer with a KRAS G12C mutation. People with this type of colon cancer who have not responded to standard therapies or for whom an experimental drug is considered appropriate may be interested in an open-label phase 1/2 study testing FMC-376, an investigational oral KRAS inhibitor. KRAS proteins control cell growth and normally cycle on and off as needed. KRAS G12C mutations are found in 3% of people with CRC and are associated with a highly aggressive disease because the G12C mutation keeps KRAS in the "on" state, leading to uncontrolled cell proliferation.
People in the study will take oral capsules of FMC-376 for up to approximately 2 years. Study sites in Texas, Utah, and Virginia started recruiting 403 participants with solid tumors in February 2024. The primary outcomes are dose-limiting toxicities and adverse events. Overall and progression-free s urvival over approximately 2 years is a secondary measure, and the trial does not measure QoL. More details at clinicaltrials.gov
Goldberg said that the drug has shown potential activity in animal models so far. "Since this is an early-stage trial, no information on [the drug's] efficacy in humans with tumors is available," said Goldberg.
Untreated metastatic CRC with a KRAS or NRAS mutation. Adult patients may be able to join an open-label, randomized phase 2 trial to determine the best dose of investigational oral PLK1 inhibitor onvansertib when given in combination with standard-of-care therapy. PLK1 controls mitosis and is overexpressed in many cancers.
Participants in the study are assigned to one of six groups and will receive study medication for up to approximately 1 year. Two groups of people will receive standard-of-care alone: Either bevacizumab (Avastin) plus FOLFIRI (irinotecan, fluorouracil, and leucovorin) or bevacizumab plus FOLFOX (leucovorin, fluorouracil, and oxaliplatin) by IV every 2 weeks. Two more groups will receive the FOLFIRI-based regimen plus oral onvansertib 10 days out of every 28 days at a dose of either 20 or 30 mg/d. The remaining individuals will receive the FOLFOX-based standard care plus one of the two onvansertib doses.
Sites in 16 mainland states plus Hawaii opened their doors in February 2024 seeking 90 participants; a center in Texas is also gearing up. Objective response rate is the primary outcome, overall survival is a secondary measure, and QoL is not assessed. More details at clinicaltrials.gov
"Testing a new drug like this one so early on in treatment is unusual and based on highly promising results in patients with refractory disease," said Goldberg. He said the approach "is one of the most promising agents in development for this poor prognosis tumor type."
Unresectable advanced or metastatic CRC with a KRAS G12V mutation and positive for HLA-A*11:01. Individuals with this type of CRC who have tried at least one line of standard systemic therapy may be interested in a randomized open-label phase 1/2 study to see if an investigational product called AFNT-211 can safely shrink their tumors. AFNT-211 is a cellular therapy consisting of the patient's own CD8+ and CD4+ T-cells that have been engineered to hone in on three types of tumor cell receptors, allowing the T-cells to better target and destroy the cancer.
Participants in the study will have their T-cells harvested through an IV catheter. A few weeks later, everyone will receive a one-time infusion of their own engineered cells. In the dose-escalation phase, 20 participants will be given different doses to test which dose gives the best response within tolerable limits. In the dose-expansion phase, different patients will receive the chosen dose.
Centers in California, New York, and Tennessee started recruiting for the trial's 100 participants with a solid tumor in March 2024. The primary outcomes are the optimal biological dose, the recommended dose for the phase 2 study, and various safety measures. Overall survival over 5 years is a secondary measure, and the investigators are not tracking QoL. More details at clinicaltrials.gov
"This is the initial study in humans designed to understand the safety of this intervention while also monitoring it for efficacy," said Goldberg, who cautioned again that the trial involves intensive therapy with the potential for serious side effects.
Unresectable, locally advanced, or metastatic colon cancer with mesothelin expression. Adults facing this clinical scenario who have received prior standard therapy may be eligible for another cellular therapy trial, this time an open-label, single-group phase 1/2 investigation of CAR T-cell product A2B694. As with all T-cell therapies, participants will undergo T-cell harvesting and then receive a single IV infusion of their modified T-cells.
Centers in California, Florida, Minnesota, Missouri, and New York began welcoming the planned 230 trial participants with a range of solid tumors in April 2024. An additional site in Massachusetts is planned. The primary outcomes of the phase 1 study are toxicities and the recommended phase-2 dose. In the phase 2 study, the primary endpoint is ORR; overall survival and QoL are not being measured. More details at clinicaltrials.gov
"This is the initial testing of this specific approach in patients, although patients have responded to similar approaches using this technology," Goldberg said. "The treatment is intensive and has the potential for substantial side effects requiring treatment at centers skilled in this approach."
All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).Goldberg was not involved with any of these trials.