New Trials in Non-CRC GI Cancers: Could Your Patient Benefit?

Several new clinical trials in noncolorectal gastrointestinal cancer have started recruiting in recent months. Maybe one of your patients could benefit from taking part.

Locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. People with one of these illnesses who have not received systemic treatment for advanced disease are eligible for a randomized, open-label, phase 3 clinical trial of a combination of domvanalimab, zimberelimab, and standard chemotherapy. Domvanalimab (from Gilead Sciences) is an experimental immune checkpoint inhibitor, and zimberelimab (from Arcus Biosciences) is an investigational angiogenesis inhibitor. For approximately 15 months, participants in the control arm will receive nivolumab plus standard chemotherapy every 2 weeks or every 3 weeks. People in the experimental group will receive domvanalimab plus zimberelimab every 4 weeks and chemotherapy every 2 weeks or the domvanalimab-zimberelimab-chemo combination once every 3 weeks. Sites in 13 states started recruiting in November 2022; the trialists aim to enroll 970 participants. The primary outcome measure is overall survival (OS). Quality of life (QoL) will not be tracked. More details at clinicaltrials.gov

When ask to comment on this study, Richard Goldberg, MD, professor emeritus at West Virginia University Cancer Institute, said, "The domvanalimab and zimberelimab combination with chemotherapy has shown promising results in trials performed with patients who have advanced lung cancer. The toxicity profiles of the two regimens that are being compared seem comparable in cross-study comparisons reported to date. This is an attractive trial for eligible patients."

Pancreatic cancer with cachexia and elevated human growth differentiation factor 15 (GDF15). Adult patients with this disease who are not receiving tube or parenteral nutrition are being recruited for a randomized, double-blind, placebo-controlled, phase 2 study of ponsegromab (from Pfizer), a monoclonal antibody directed against GDF15. The mechanisms of cancer cachexia are not well understood, but cachexia is correlated with elevated circulating GDF15. During the initial 12-week, double-blind study, participants will receive three subcutaneous injections of either ponsegromab or placebo 4 weeks apart. An optional open-label study will follow. In that study, all participants can receive ponsegromab every 4 weeks for a year. The study opened in November 2022 at centers in California, Texas, Washington, Japan, and China. The investigators are planning for 168 participants who have one of a range of cancers. Six other US states and three other countries are gearing up. The primary outcome is change in body weight. QoL is a secondary outcome, and OS will not be tracked. More details at clinicaltrials.gov

Goldberg commented that with the placebo-controlled design, participants will have a 50:50 chance of receiving the experimental drug at the start. This is possible because there is no standard treatment in this setting. "Other options that are approved are alternatives to enrollment in this study, but those alternatives have limited efficacy," Goldberg said.

Unresectable, locally advanced/metastatic pancreatic or biliary tract cancer. Adults with these types of cancer who have received all available conventional therapies or, in the case of biliary tract cancer, are not likely to tolerate or benefit from the standard of care can join an open-label, single-arm, phase 2 study of the investigational agent BI 907828 (from Boehringer Ingelheim). This drug reactivates the P53 tumor-suppressor gene. Mutations in p53, found in most cancers, lead to uncontrollable cell division. Participants will swallow a tablet of BI 907828 once every 3 weeks until disease progression, unacceptable toxicities, or death, whichever arrives first. The trial opened in November 2022 at the Sibley Memorial Hospital, Washington, DC, and at six sites in Asia and Europe. Researchers anticipate enrolling 130 participants with one of several solid tumors. The primary outcome measure is objective response rate. OS and QoL are secondary outcomes. More details at clinicaltrials.gov

Goldberg said, "Preliminary studies have shown responses in sarcoma patients with P53 mutations. Other studies are currently underway that combine this drug with standard chemotherapy agents. The primary side effects appear to be nausea and vomiting and depression of WBC [white blood cell] and platelet counts that can predispose patients to infection or bleeding. This study does provide an additional option for patients with treatment-refractory disease looking for additional therapies."

Unresectable advanced, metastatic, or recurrent biliary tract cancers. Patients in this position whose disease has progressed after treatment with gemcitabine and platinum may be interested in a randomized, controlled, phase 2/3 clinical trial comparing investigational bifunctional antibody CTX-009 (from Compass Therapeutics) plus paclitaxel to paclitaxel alone. CTX-009 targets angiogenesis, which tumors require to grow and spread. All participants will receive intravenous (IV) infusions of paclitaxel weekly for 3 weeks out of every 4 until the disease progresses or the therapy becomes intolerable, whichever happens first, or the person dies. People in the experimental arm will also receive IV infusions of CTX-009 every 2 weeks. Study centers in Colorado, Delaware, New Jersey, New Mexico, New York, South Carolina, Texas, and Washington started recruiting in January 2023, with a site in Missouri to follow. The trialists aim to enroll 150 participants. Best overall response is the primary endpoint; OS over 1 year and QoL are secondary endpoints. More details at clinicaltrials.gov

Goldberg noted that a South Korean study testing CTX-009 plus paclitaxel in a similar patient population showed "high response rates of 37.5 % and a promising median overall survival of more than 12 months," with predictable toxicity. "This study is being repeated in the US with a larger number of patients," Goldberg said. "This is an appealing experimental option for fit patients who meet the trial eligibility criteria."

Child-Pugh A or B cirrhosis with advanced hepatocellular carcinoma. Individuals with this type of liver cancer and, in the case of Child-Pugh A cirrhosis whose condition has failed to improve with or who are intolerant of at least two systemic therapies can enroll in a randomized, controlled, phase 2 National Cancer Institute study. The trial is testing whether an electromagnetic device called TheraBionic improves survival. TheraBionic consists of a spoon-shaped antenna that is held in the patient's mouth and that floods the body with a low-level radiofrequency-electromagnetic field modulated to target liver tumor cells. For up to 2 years, participants will give themselves three 1-hour treatments per day. People in the control group will use a device that emits nontherapeutic frequencies. Research sites in Florida, Illinois, North Carolina, Oregon, Pennsylvania, and Texas will start recruiting in May 2023. The researchers plan to enroll 166 participants. The primary endpoints are OS and QoL. More details at clinicaltrials.gov

Commenting on this trial, Goldberg said, "This is a novel approach with no real track record in this setting but could be an appealing study for individuals who are interested in pursuing further options after their tumor has progressed on two prior lines of therapy and who find a device study more appealing than a drug study." Although experience with the device is limited, he predicted that it is unlikely to result in significant side effects, especially in comparison to new medical therapies.

Gastrointestinal cancers. Adults aged 70 or younger who have these types of cancer are eligible for a phase 2 National Cancer Institute study of autologous T-cell receptor (TCR) gene therapy. Unlike CAR T-cell therapy, which only reaches the 20% of cancer neoantigens that are expressed extracellularly, TCR technology can target the 80% of abnormal proteins that are expressed inside cancer cells. Participants will receive a single infusion of their own engineered T cells. If their condition responds, they will attend follow-up visits every 3–6 months for 3 years, then join a long-term study in which they will be followed for 12 more years. The National Institutes of Health's Clinical Center, in Bethesda, Maryland, started recruiting 210 participants with one of a selection of solid cancers in April 2022. Response rate, measured by objective tumor regression, is the primary endpoint. OS and QoL will not be tracked. More details at clinicaltrials.gov

"Studies like this have potential to help a patient, and the personalized approach is appealing, although the approach is early in its testing," commented Goldberg.

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.

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Cite this: New Trials in Non-CRC GI Cancers: Could Your Patient Benefit? - Medscape - Apr 07, 2023.