Rindopepimut (CDX-110)

Property	Information
Drug Name	Rindopepimut (CDX-110)
FDA Approval	Not FDA-approved; received Breakthrough Therapy designation for glioblastoma in Feb 2015
Used for	EGFRvIII-positive Glioblastoma Multiforme (GBM) in newly diagnosed and recurrent cases
Clinical Trial Phase	Phase III for newly diagnosed GBM was discontinued; Phase II for recurrent GBM showed promising results
Clinical Trial Explanation	Not specified
Common Side Effects	Transient, low-grade local reactions; overall well-tolerated
OS without	Median overall survival with standard treatment ranges around 15-17 months for newly diagnosed GBM
OS with	Phase III ACT IV trial did not show a significant increase in OS; however, a Phase II trial (ReACT) in recurrent GBM showed improved outcomes with bevacizumab
PFS without	Standard treatments offer a median PFS of about 6.9 months
PFS with	ReACT trial showed a 6-month PFS of 28% for the rindopepimut group compared to 16% for the control
Usefulness Rating	3
Usefulness Explanation	While initial phase III trial results in newly diagnosed GBM were disappointing, the ReACT trial for recurrent GBM suggests potential benefits, particularly when combined with bevacizumab
Toxicity Level	2
Toxicity Explanation	Primarily associated with injection site reactions and overall shows a favorable safety profile

Links: https://jeccr.biomedcentral.com/articles/10.1186/s13046-020-01760-2, https://aacrjournals.org/clincancerres/article/26/7/1586/474795, https://en.wikipedia.org/wiki/Rindopepimut

From Ben Williams Book: A very different approach to developing a treatment vaccine, which has the virtue of being usable "off-the-shelf”, without modification for individual patients, targets a mutation of the epidermal growth factor receptor, known as variant III, which occurs in 25-40% of GBMs. One reason that EGFR inhibitors such as Iressa have not been more effective is that they target the normal EGFR receptor, not this mutated receptor. EGFR variant III is also rarely seen in anything other than GBM tumors. To be eligible for the trial, patients must first be tested whether they possess the mutation.

Disappointing news was delivered by Celldex in a press release dated March 7, 2016, when the company announced that the phase III ACT IV clinical trial of rindopepimut for newly diagnosed glioblastoma patients with minimal disease would be discontinued, after an independent review board found that the trial was unlikely to meet its primary endpoint (improved overall survival). Although survival results were consistent with previous phase II trials, the control arm in this trial had survival outcomes that were better than expected (median overall survival was 20.4 months in the rindopepimut arm and 21.1 months in the control arm, hazard ratio = 0.99).

Rindopepimut is also being tested in a randomized phase II trial for recurrent glioblastoma called ReACT, in combination with Avastin. Data presented at the ASCO 2015 meeting showed that the primary endpoint of the trial (six month progression-free survival) was met. PFS-6 was 30% in the rindopepimut + Avastin arm, versus 12% in the control arm (per protocol). Additional data (reference 340, abstract IMCT-08) was presented later in 2015 at the SNO meeting, where it was reported that overall survival was also significantly improved and 2-year survival was 25% for the rindopepimut arm versus 0% in the control arm. Patients receiving rindopepimut had also reduced dependency on steroids, as 33% of patients were able to cease steroid treatment for six months or longer, versus none in the control group.

While the development of Rintega (rindopepimut) as a first-line treatment for GBM is

unlikely to continue given these trial results, the therapy still holds promise combined with Avastin in the recurrent setting, according to the outcomes of the ReACT trial.Property "Has original text" (as page type) with input value "A very different approach to developing a treatment vaccine, which has the virtue of</br>being usable "off-the-shelf”, without modification for individual patients, targets a</br>mutation of the epidermal growth factor receptor, known as variant III, which occurs in</br>25-40% of GBMs. One reason that EGFR inhibitors such as Iressa have not been more</br>effective is that they target the normal EGFR receptor, not this mutated receptor. EGFR</br>variant III is also rarely seen in anything other than GBM tumors. To be eligible for the</br>trial, patients must first be tested whether they possess the mutation.</br></br>Disappointing news was delivered by Celldex in a press release dated March 7, 2016,</br>when the company announced that the phase III ACT IV clinical trial of rindopepimut for</br>newly diagnosed glioblastoma patients with minimal disease would be discontinued, after</br>an independent review board found that the trial was unlikely to meet its primary</br>endpoint (improved overall survival). Although survival results were consistent with</br>previous phase II trials, the control arm in this trial had survival outcomes that were</br>better than expected (median overall survival was 20.4 months in the rindopepimut arm</br>and 21.1 months in the control arm, hazard ratio = 0.99).</br></br>Rindopepimut is also being tested in a randomized phase II trial for recurrent</br>glioblastoma called ReACT, in combination with Avastin. Data presented at the ASCO</br>2015 meeting showed that the primary endpoint of the trial (six month progression-free</br>survival) was met. PFS-6 was 30% in the rindopepimut + Avastin arm, versus 12% in the</br>control arm (per protocol). Additional data (reference 340, abstract IMCT-08) was</br>presented later in 2015 at the SNO meeting, where it was reported that overall survival</br>was also significantly improved and 2-year survival was 25% for the rindopepimut arm</br>versus 0% in the control arm. Patients receiving rindopepimut had also reduced</br>dependency on steroids, as 33% of patients were able to cease steroid treatment for six</br>months or longer, versus none in the control group.</br></br>While the development of Rintega (rindopepimut) as a first-line treatment for GBM is</br></br>unlikely to continue given these trial results, the therapy still holds promise combined</br>with Avastin in the recurrent setting, according to the outcomes of the ReACT trial." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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