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A small molecule can provide a “clinically meaningful reduction” in severe oral mucositis without affecting tumor control in head and neck cancer, according to an investigator from a phase 2 trial.
The molecule, GC4419 (avasopasem manganese), is designed to convert superoxide to hydrogen peroxide and oxygen, thereby protecting normal tissue from damage associated with radiotherapy.
Investigators tested GC4419 in a phase 2 trial of patients with locally advanced oral cavity or oropharynx cancer who received intensity-modulated radiotherapy plus cisplatin. Initial results from this trial were published in December (J Clin Oncol. 2019 Dec 1;37[34]:3256-65).
Carryn M. Anderson, MD, of University of Iowa Hospitals & Clinics in Iowa City, presented updated results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.
The trial (NCT02508389) enrolled 223 patients scheduled to be treated with intensity-modulated radiotherapy (60-72 Gy or greater than 50 Gy to more than two oral sites) plus cisplatin (weekly or every 3 weeks).
The patients were randomized to receive 30 mg of GC4419 (n = 73), 90 mg of GC4419 (n = 76), or placebo (n = 74) intravenously over 60 minutes prior to each radiotherapy fraction. Baseline patient and tumor characteristics were well balanced among the treatment arms.
Efficacy and safety
The study’s primary endpoint was the duration of severe oral mucositis. When compared with placebo, the 90-mg dose of GC4419 conferred a 92% reduction in median days of severe oral mucositis (P = .024).
The 90-mg dose of GC4419 also reduced the incidence of severe oral mucositis by 34% (P = .009) and the rate of grade 4 oral mucositis by 47% (P = .045) when compared with placebo.
“GC4419, particularly the 90-mg dosage, provides a clinically meaningful reduction in severe oral mucositis duration, incidence, and severity,” Dr. Anderson noted.
“Safety was comparable across study arms,” she added. “The most frequent adverse events were those already expected with cisplatin and radiation, and those were not worsened in any way by the addition of this drug.”
Adverse events expected with GC4419 were “mild and transient,” according to Dr. Anderson. These events included syncope, hypotension/orthostasis, and oral/facial paresthesia.
Grade 3 syncope occurred in 4% of patients in the placebo arm, 4% in the 30-mg arm, and 6% in the 90-mg arm. Grade 3 hypotension/orthostasis occurred in 6%, 4%, and 4%, respectively. Grade 1 oral/facial paresthesia occurred in 15%, 10%, and 19%, respectively.
Long-term outcomes
“The 1- and 2-year tumor control is similar with utilization of [GC4419], and this is consistent with the drug’s known mechanism and previous animal models,” Dr. Anderson said.
At 1 and 2 years, there were no significant differences between the treatment arms with regard to locoregional control, distant metastasis, progression-free survival, or overall survival.
The 1-year progression-free survival was 82% in the placebo arm, 86% in the 30-mg arm, and 80% in the 90-mg arm. The 1-year overall survival was 93%, 91%, and 88%, respectively.
The 2-year progression-free survival was 77% in the placebo arm, 76% in the 30-mg arm, and 77% in the 90-mg arm. The 1-year overall survival was 87%, 85%, and 86%, respectively.
From trials to practice
Despite the favorable results of this trial, meeting attendees expressed concerns that the administration of GC4419 may not be feasible in real-life because it is labor- and resource-intensive.
“Methodologically, the study was excellent,” said attendee Shahid Iqbal, MBBS, a consultant clinical oncologist at Newcastle upon Tyne Hospitals NHS Foundation Trust in the United Kingdom, who was not involved in this trial.
Dr. Iqbal noted that this placebo-controlled trial had a “very reasonable number of patients in each arm,” the 90-mg dose of GC4419 was “effective,” and the drug had “no adverse impact on survival.”
“However, in my personal opinion, this intravenous infusion on a daily basis is not feasible in real life,” Dr. Iqbal said. “I cannot see this becoming a standard of care in National Health Service UK. This is simply not cost-effective at all.”
Although she didn’t address costs, Dr. Anderson did acknowledge that administering GC4419 is labor intensive.
“But we are hopeful that, if this drug ultimately makes it to [Food and Drug Administration] approval, the efficacy benefits we are showing will make the work flow changes worthwhile,” she said. “We certainly have shown that, in this study, 44 institutions could make that happen. At the University of Iowa, we found it easiest to institute an infusion space within the department of radiation oncology rather than relying on our medical oncology colleagues to let us borrow a chair.”
GC4419 is now under investigation in a phase 3 trial (NCT03689712) and has received fast track and breakthrough therapy designations from the FDA.
The phase 2 trial was sponsored by Galera Therapeutics. Dr. Anderson is an uncompensated research adviser to the company. Dr. Iqbal has no relevant conflicts of interest.
SOURCE: Anderson CM et al. Head and Neck Cancer Symposium. Abstract LBA 2.
A small molecule can provide a “clinically meaningful reduction” in severe oral mucositis without affecting tumor control in head and neck cancer, according to an investigator from a phase 2 trial.
The molecule, GC4419 (avasopasem manganese), is designed to convert superoxide to hydrogen peroxide and oxygen, thereby protecting normal tissue from damage associated with radiotherapy.
Investigators tested GC4419 in a phase 2 trial of patients with locally advanced oral cavity or oropharynx cancer who received intensity-modulated radiotherapy plus cisplatin. Initial results from this trial were published in December (J Clin Oncol. 2019 Dec 1;37[34]:3256-65).
Carryn M. Anderson, MD, of University of Iowa Hospitals & Clinics in Iowa City, presented updated results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.
The trial (NCT02508389) enrolled 223 patients scheduled to be treated with intensity-modulated radiotherapy (60-72 Gy or greater than 50 Gy to more than two oral sites) plus cisplatin (weekly or every 3 weeks).
The patients were randomized to receive 30 mg of GC4419 (n = 73), 90 mg of GC4419 (n = 76), or placebo (n = 74) intravenously over 60 minutes prior to each radiotherapy fraction. Baseline patient and tumor characteristics were well balanced among the treatment arms.
Efficacy and safety
The study’s primary endpoint was the duration of severe oral mucositis. When compared with placebo, the 90-mg dose of GC4419 conferred a 92% reduction in median days of severe oral mucositis (P = .024).
The 90-mg dose of GC4419 also reduced the incidence of severe oral mucositis by 34% (P = .009) and the rate of grade 4 oral mucositis by 47% (P = .045) when compared with placebo.
“GC4419, particularly the 90-mg dosage, provides a clinically meaningful reduction in severe oral mucositis duration, incidence, and severity,” Dr. Anderson noted.
“Safety was comparable across study arms,” she added. “The most frequent adverse events were those already expected with cisplatin and radiation, and those were not worsened in any way by the addition of this drug.”
Adverse events expected with GC4419 were “mild and transient,” according to Dr. Anderson. These events included syncope, hypotension/orthostasis, and oral/facial paresthesia.
Grade 3 syncope occurred in 4% of patients in the placebo arm, 4% in the 30-mg arm, and 6% in the 90-mg arm. Grade 3 hypotension/orthostasis occurred in 6%, 4%, and 4%, respectively. Grade 1 oral/facial paresthesia occurred in 15%, 10%, and 19%, respectively.
Long-term outcomes
“The 1- and 2-year tumor control is similar with utilization of [GC4419], and this is consistent with the drug’s known mechanism and previous animal models,” Dr. Anderson said.
At 1 and 2 years, there were no significant differences between the treatment arms with regard to locoregional control, distant metastasis, progression-free survival, or overall survival.
The 1-year progression-free survival was 82% in the placebo arm, 86% in the 30-mg arm, and 80% in the 90-mg arm. The 1-year overall survival was 93%, 91%, and 88%, respectively.
The 2-year progression-free survival was 77% in the placebo arm, 76% in the 30-mg arm, and 77% in the 90-mg arm. The 1-year overall survival was 87%, 85%, and 86%, respectively.
From trials to practice
Despite the favorable results of this trial, meeting attendees expressed concerns that the administration of GC4419 may not be feasible in real-life because it is labor- and resource-intensive.
“Methodologically, the study was excellent,” said attendee Shahid Iqbal, MBBS, a consultant clinical oncologist at Newcastle upon Tyne Hospitals NHS Foundation Trust in the United Kingdom, who was not involved in this trial.
Dr. Iqbal noted that this placebo-controlled trial had a “very reasonable number of patients in each arm,” the 90-mg dose of GC4419 was “effective,” and the drug had “no adverse impact on survival.”
“However, in my personal opinion, this intravenous infusion on a daily basis is not feasible in real life,” Dr. Iqbal said. “I cannot see this becoming a standard of care in National Health Service UK. This is simply not cost-effective at all.”
Although she didn’t address costs, Dr. Anderson did acknowledge that administering GC4419 is labor intensive.
“But we are hopeful that, if this drug ultimately makes it to [Food and Drug Administration] approval, the efficacy benefits we are showing will make the work flow changes worthwhile,” she said. “We certainly have shown that, in this study, 44 institutions could make that happen. At the University of Iowa, we found it easiest to institute an infusion space within the department of radiation oncology rather than relying on our medical oncology colleagues to let us borrow a chair.”
GC4419 is now under investigation in a phase 3 trial (NCT03689712) and has received fast track and breakthrough therapy designations from the FDA.
The phase 2 trial was sponsored by Galera Therapeutics. Dr. Anderson is an uncompensated research adviser to the company. Dr. Iqbal has no relevant conflicts of interest.
SOURCE: Anderson CM et al. Head and Neck Cancer Symposium. Abstract LBA 2.
A small molecule can provide a “clinically meaningful reduction” in severe oral mucositis without affecting tumor control in head and neck cancer, according to an investigator from a phase 2 trial.
The molecule, GC4419 (avasopasem manganese), is designed to convert superoxide to hydrogen peroxide and oxygen, thereby protecting normal tissue from damage associated with radiotherapy.
Investigators tested GC4419 in a phase 2 trial of patients with locally advanced oral cavity or oropharynx cancer who received intensity-modulated radiotherapy plus cisplatin. Initial results from this trial were published in December (J Clin Oncol. 2019 Dec 1;37[34]:3256-65).
Carryn M. Anderson, MD, of University of Iowa Hospitals & Clinics in Iowa City, presented updated results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.
The trial (NCT02508389) enrolled 223 patients scheduled to be treated with intensity-modulated radiotherapy (60-72 Gy or greater than 50 Gy to more than two oral sites) plus cisplatin (weekly or every 3 weeks).
The patients were randomized to receive 30 mg of GC4419 (n = 73), 90 mg of GC4419 (n = 76), or placebo (n = 74) intravenously over 60 minutes prior to each radiotherapy fraction. Baseline patient and tumor characteristics were well balanced among the treatment arms.
Efficacy and safety
The study’s primary endpoint was the duration of severe oral mucositis. When compared with placebo, the 90-mg dose of GC4419 conferred a 92% reduction in median days of severe oral mucositis (P = .024).
The 90-mg dose of GC4419 also reduced the incidence of severe oral mucositis by 34% (P = .009) and the rate of grade 4 oral mucositis by 47% (P = .045) when compared with placebo.
“GC4419, particularly the 90-mg dosage, provides a clinically meaningful reduction in severe oral mucositis duration, incidence, and severity,” Dr. Anderson noted.
“Safety was comparable across study arms,” she added. “The most frequent adverse events were those already expected with cisplatin and radiation, and those were not worsened in any way by the addition of this drug.”
Adverse events expected with GC4419 were “mild and transient,” according to Dr. Anderson. These events included syncope, hypotension/orthostasis, and oral/facial paresthesia.
Grade 3 syncope occurred in 4% of patients in the placebo arm, 4% in the 30-mg arm, and 6% in the 90-mg arm. Grade 3 hypotension/orthostasis occurred in 6%, 4%, and 4%, respectively. Grade 1 oral/facial paresthesia occurred in 15%, 10%, and 19%, respectively.
Long-term outcomes
“The 1- and 2-year tumor control is similar with utilization of [GC4419], and this is consistent with the drug’s known mechanism and previous animal models,” Dr. Anderson said.
At 1 and 2 years, there were no significant differences between the treatment arms with regard to locoregional control, distant metastasis, progression-free survival, or overall survival.
The 1-year progression-free survival was 82% in the placebo arm, 86% in the 30-mg arm, and 80% in the 90-mg arm. The 1-year overall survival was 93%, 91%, and 88%, respectively.
The 2-year progression-free survival was 77% in the placebo arm, 76% in the 30-mg arm, and 77% in the 90-mg arm. The 1-year overall survival was 87%, 85%, and 86%, respectively.
From trials to practice
Despite the favorable results of this trial, meeting attendees expressed concerns that the administration of GC4419 may not be feasible in real-life because it is labor- and resource-intensive.
“Methodologically, the study was excellent,” said attendee Shahid Iqbal, MBBS, a consultant clinical oncologist at Newcastle upon Tyne Hospitals NHS Foundation Trust in the United Kingdom, who was not involved in this trial.
Dr. Iqbal noted that this placebo-controlled trial had a “very reasonable number of patients in each arm,” the 90-mg dose of GC4419 was “effective,” and the drug had “no adverse impact on survival.”
“However, in my personal opinion, this intravenous infusion on a daily basis is not feasible in real life,” Dr. Iqbal said. “I cannot see this becoming a standard of care in National Health Service UK. This is simply not cost-effective at all.”
Although she didn’t address costs, Dr. Anderson did acknowledge that administering GC4419 is labor intensive.
“But we are hopeful that, if this drug ultimately makes it to [Food and Drug Administration] approval, the efficacy benefits we are showing will make the work flow changes worthwhile,” she said. “We certainly have shown that, in this study, 44 institutions could make that happen. At the University of Iowa, we found it easiest to institute an infusion space within the department of radiation oncology rather than relying on our medical oncology colleagues to let us borrow a chair.”
GC4419 is now under investigation in a phase 3 trial (NCT03689712) and has received fast track and breakthrough therapy designations from the FDA.
The phase 2 trial was sponsored by Galera Therapeutics. Dr. Anderson is an uncompensated research adviser to the company. Dr. Iqbal has no relevant conflicts of interest.
SOURCE: Anderson CM et al. Head and Neck Cancer Symposium. Abstract LBA 2.
REPORTING FROM HEAD AND NECK CANCERS SYMPOSIUM 2020