EGFR-targeting trial or Tagrisso?

Looking at a possible clinical trial for my husband with an ADC (antibody-drug conjugate) called ABBV-321 that targets EGFR.  The trial has identified a maximum dose and is now in the expanded safety phase.  Any one know anything about this?  https://clinicaltrials.gov/ct2/show/NCT03234712

My husband's tumor is showing progression, so if he's deemed eligible for the trial then we'd be choosing between the trial or a combo of CCNU/Avastin/Tagrisso (the latter to target that EGFR amplification).  Choices, choices....

Chloroquine and non-P53, non-EGFR mutant tumors

I know that chloroquine has been discussed to death in this site and the original message board but I couldn't find an answer to my question there and am hoping someone can provide some insight.

My understanding is that chloroquine generally works best for those with EGRF mutations. My wife does not have this.

It's a bit unclear as I came across another post in another site (that I cannot find again) that seemed to say that chloroquine works better for those with a P53 mutation while other posts, particularly Stephen's comment in this post, noted that it works better for those without a P53 mutation. I note that we also have a PTEN loss as well.

Finally, this post noted that Chloroquine provides a "strong antimutagenic effect" but it's unclear if it's universally so or if it's only for those that with the aforementioned mutations.

Question: If someone has both a non-P53 and a non-EGFR mutant tumor, is it worth adding Chloroquine if we're past radiation and chemotherapy? We are currently on Optune and Nivo along with our cocktail.

Followup Questions: For those on chloroquine, has anyone noticed any side-effects beyond the retinopathy issue?

My wife's pill burden is heavy enough so I have to be judicious in what we add. I am most drawn to Chloquine because it's one pill, seems to have few side effects, and is a small pill at that.

CARIS report

Hi,

This is part of the CARIS report of my brothers tumour. We are looking into further drugs for him to take. Can anyone offer any advice from this information? I have 12 pages of results but unfortunately the Dr hasn't offered any advice!Thanks, Lisa



PAGE 2 of 12

Biomarker	Method	Result
EGFR	IHC	Positive
MGMT	Pyro SEQ	Methylated
PD-1 IHC	IHC	Positive
RRM1	IHC	Negative

Biomarker	Method	Result
TLE3	IHC	Positive
TOPO1	IHC	Positive
TS	IHC	Negative

Withholding temozolomide in glioblastoma patients with unmethylated MGMT promoter

http://neuro-oncology.oxfordjournals.org/content/early/2015/09/14/neuonc.nov198.extract

Will add to the brain tumor Library.

Quote from Hegi and Stupp:

"Together, the data allow the conclusion that alkylating agent chemotherapy is of marginal benefit, if any, for patients with MGMT unmethylated GBM. By continuing to treat the majority of MGMT unmethylated patients with TMZ, we are missing an opportunity to do better."

Keep in mind that this was written by the lead investigators of the 2005 trial that led to TMZ becoming standard of care for newly diagnosed GBM.  The writing is on the wall.  Soon there will be two standards of care for ndGBM based on MGMT status.  It make take a few years, but patients with unmethylated MGMT status deserve something better.

However, this editorial did not consider the potential to sensitize these tumors to TMZ using agents that inhibit MGMT, or the potential of metronomic schedule TMZ in cases with EGFR overexpression. I wouldn't suggest abandoning TMZ altogether for these patients, but the current protocol does need to be tweaked for these patients (obviously).

Should we take chloroquine

I just looked at the new pdf posted by Ben Williams and it states there that addition of it to the standard treatment did not produce any benefit except for tumors with egfr3. So  I am quite confused now if we should take it or not since our tumor is tp53 mutated , might have pten loss but no egfr3.