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A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer.

Kim SB, Ahn JH, Kim J, Jung KH - Mol Ther Methods Clin Dev (2015)

Bottom Line: One subject showed a partial response, and seven subjects had stable diseases.However, there were no differences in clinical tumor response and HER2-specific immune responses among the cohorts.These results showed that intramuscular injections of pHM-GM-CSF and Ad-HM were well tolerated and safe.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine , Songpa-Gu, Seoul, Korea.

ABSTRACT
A phase 1 clinical trial was conducted to assess the safety, tolerability, and preliminary efficacy of a heterologous prime-boost strategy involving plasmid DNA (pHM-GM-CSF, expressing truncated human epidermal growth factor receptor 2 (HER2) and granulocyte macrophage colony-stimulation factor (GM-CSF) as a bicistronic message) and an adenoviral vector (Ad-HM, containing the same modified HER2 sequence only), in patients with stage III-IV metastatic breast cancer expressing HER2. Nine eligible subjects were divided into three cohorts based on the dosages (2, 4, and 8 mg/patient/visit) of pHM-GM-CSF used as the primer, which was intramuscularly injected three times at weeks 0, 2, and 4. It was followed by a single injection of Ad-HM (3 × 10(9) virus particles), used as a booster, at week 6. During the 6-month follow-up period, adverse events (AEs), pharmacokinetics and pharmacodynamics, and HER2-specific cellular and humoral immune responses were evaluated. Seven cases of minor grade 1 toxicities in four of nine subjects and no serious drug-related AEs were reported. HER2-specific cell-mediated or humoral immunity was produced in all (100%) or three subjects (33%), respectively. One subject showed a partial response, and seven subjects had stable diseases. However, there were no differences in clinical tumor response and HER2-specific immune responses among the cohorts. These results showed that intramuscular injections of pHM-GM-CSF and Ad-HM were well tolerated and safe.

No MeSH data available.


Related in: MedlinePlus

A dose-escalation study of pHM-GM-CSF. Subjects were immunized with 2, 4, or 8 mg of pHM-GM-CSF at weeks 0, 2, and 4 and then boosted with 3 × 109 VP of Ad-HM at week 6. All adverse events were monitored at every visit and evaluated during the study period. The samples for measuring pharmacokinetics (the presence of HER2 and GM-CSF proteins and Ad-HM vector), GM-CSF autoantibody, and immunological response to HER2 (humoral and cell-mediated immunities) were collected periodically during the study.
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fig1: A dose-escalation study of pHM-GM-CSF. Subjects were immunized with 2, 4, or 8 mg of pHM-GM-CSF at weeks 0, 2, and 4 and then boosted with 3 × 109 VP of Ad-HM at week 6. All adverse events were monitored at every visit and evaluated during the study period. The samples for measuring pharmacokinetics (the presence of HER2 and GM-CSF proteins and Ad-HM vector), GM-CSF autoantibody, and immunological response to HER2 (humoral and cell-mediated immunities) were collected periodically during the study.

Mentions: Sixteen subjects with breast cancer who provided informed consent form were screened for eligibility. Nine eligible subjects were subsequently assigned to cohorts 1, 2, or 3 (three subjects per cohort). As shown in Figure 1, nine subjects were treated with three different doses of pHM-GM-CSF (6, 12, and 24 mg for cohorts 1, 2, and 3, respectively) and a single dose of Ad-HM (3 × 109 virus particles (VP)). Each subject received pHM-GM-CSF intramuscularly on weeks 0, 2, and 4, followed by one Ad-HM injection 2 weeks later (on week 6). The dose-escalation decision and permission to administer at a higher dose were made by the data safety monitoring board, which independently evaluated the occurrence of adverse drug reactions and dose-limiting toxicity of the last subject of each cohort at 8 weeks post-injection.


A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer.

Kim SB, Ahn JH, Kim J, Jung KH - Mol Ther Methods Clin Dev (2015)

A dose-escalation study of pHM-GM-CSF. Subjects were immunized with 2, 4, or 8 mg of pHM-GM-CSF at weeks 0, 2, and 4 and then boosted with 3 × 109 VP of Ad-HM at week 6. All adverse events were monitored at every visit and evaluated during the study period. The samples for measuring pharmacokinetics (the presence of HER2 and GM-CSF proteins and Ad-HM vector), GM-CSF autoantibody, and immunological response to HER2 (humoral and cell-mediated immunities) were collected periodically during the study.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588449&req=5

fig1: A dose-escalation study of pHM-GM-CSF. Subjects were immunized with 2, 4, or 8 mg of pHM-GM-CSF at weeks 0, 2, and 4 and then boosted with 3 × 109 VP of Ad-HM at week 6. All adverse events were monitored at every visit and evaluated during the study period. The samples for measuring pharmacokinetics (the presence of HER2 and GM-CSF proteins and Ad-HM vector), GM-CSF autoantibody, and immunological response to HER2 (humoral and cell-mediated immunities) were collected periodically during the study.
Mentions: Sixteen subjects with breast cancer who provided informed consent form were screened for eligibility. Nine eligible subjects were subsequently assigned to cohorts 1, 2, or 3 (three subjects per cohort). As shown in Figure 1, nine subjects were treated with three different doses of pHM-GM-CSF (6, 12, and 24 mg for cohorts 1, 2, and 3, respectively) and a single dose of Ad-HM (3 × 109 virus particles (VP)). Each subject received pHM-GM-CSF intramuscularly on weeks 0, 2, and 4, followed by one Ad-HM injection 2 weeks later (on week 6). The dose-escalation decision and permission to administer at a higher dose were made by the data safety monitoring board, which independently evaluated the occurrence of adverse drug reactions and dose-limiting toxicity of the last subject of each cohort at 8 weeks post-injection.

Bottom Line: One subject showed a partial response, and seven subjects had stable diseases.However, there were no differences in clinical tumor response and HER2-specific immune responses among the cohorts.These results showed that intramuscular injections of pHM-GM-CSF and Ad-HM were well tolerated and safe.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine , Songpa-Gu, Seoul, Korea.

ABSTRACT
A phase 1 clinical trial was conducted to assess the safety, tolerability, and preliminary efficacy of a heterologous prime-boost strategy involving plasmid DNA (pHM-GM-CSF, expressing truncated human epidermal growth factor receptor 2 (HER2) and granulocyte macrophage colony-stimulation factor (GM-CSF) as a bicistronic message) and an adenoviral vector (Ad-HM, containing the same modified HER2 sequence only), in patients with stage III-IV metastatic breast cancer expressing HER2. Nine eligible subjects were divided into three cohorts based on the dosages (2, 4, and 8 mg/patient/visit) of pHM-GM-CSF used as the primer, which was intramuscularly injected three times at weeks 0, 2, and 4. It was followed by a single injection of Ad-HM (3 × 10(9) virus particles), used as a booster, at week 6. During the 6-month follow-up period, adverse events (AEs), pharmacokinetics and pharmacodynamics, and HER2-specific cellular and humoral immune responses were evaluated. Seven cases of minor grade 1 toxicities in four of nine subjects and no serious drug-related AEs were reported. HER2-specific cell-mediated or humoral immunity was produced in all (100%) or three subjects (33%), respectively. One subject showed a partial response, and seven subjects had stable diseases. However, there were no differences in clinical tumor response and HER2-specific immune responses among the cohorts. These results showed that intramuscular injections of pHM-GM-CSF and Ad-HM were well tolerated and safe.

No MeSH data available.


Related in: MedlinePlus