AMG 340 BiTE trial

[Anon2014]

I may get accepted into the AMG 340 trial and info on it is lacking. It’s been in phase 1 for about 2 years now. Can anyone here provide any information I might find useful in deciding whether to participate or not? Specifically wondering about it’s efficacy and safety?

[Tall_Allen]

That's exactly what the Phase I trial is for. Difficult decision.

[Anon2014 in reply to Tall_Allen]

I understand that’s the purpose of phase 1 trials but since the trial started over 2 years ago I was hoping someone here had some information maybe even interim results that are not readily available online.

[swwags]

I'm not a doctor - so info I provide should not be used to make medical decisions. The decision is yours.

Essentially, AMG 340 is a clinical trial that is evaluating the safety, pharmacology, and clinical activity of a new drug called AMG 340 in patients with metastatic castrate-resistant prostate cancer (mCRPC) who have undergone at least two prior treatments. AMG 340 is a bispecific antibody that binds to two different molecules, prostate-specific membrane antigen (PSMA) and CD3, on the surface of cancer cells and immune cells, respectively.

By doing so, it aims to activate T-cells to recognize and destroy cancer cells that express PSMA.The clinical trial has two parts: Arm A, which involves increasing the dosage of AMG 340 to determine the maximum tolerable dose (MTD) or recommended phase 2 dose (RP2D) in patients; and Arm B, which involves further evaluating the safety, tolerability, and pharmacokinetics (PK) of the identified MTD/RP2D in a larger group of patients.

This is an open-label study, which means that both the patients and the researchers are aware of the treatment being given. The trial is designed to test the efficacy and safety of AMG 340 as a monotherapy, without the use of any other cancer treatments.

Call them - Contact: Amgen Call Center866-572-6436 [e-mail]

Here's a link to further describe primary and secondary success measures as well as acceptance criteria and whose recruiting.

clinicaltrials.gov/ct2/show...

Phase 1 trials are as TA puts it, difficult decisions

[Anon2014 in reply to swwags]

Thanks

[mypk]

I recently asked a similar question regarding AMG-509 because I was surprised that 3 years after the start of the phase 1 study, all 25 study sites listed at the time were still marked with the status 'Recruiting' at clinicaltrials.gov. The reason probably is that the pharmaceutical company in phase 1 first has to learn what effects and side effects occur during dose finding and which are the best ways to deal with them. And so that they don't suddenly have to move 10 participants to an intensive care unit at the same time if something goes wrong, recruitment is only done in small steps, so rather one or two within a certain time slot.

Surely Amgen or the study clinic will provide you with a comprehensive patient information handout before you eventually sign a consent form to participate in the study.

[Anon2014 in reply to mypk]

I received some information but nothing even hinting at efficacy results.

[mypk in reply to Anon2014]

The final data collection date for primary outcome measure is scheduled for September 2024. Because the study is still recruiting (100 participants) and the company hasn't announced a date for an intermediate data readout yet, my guess would be that we won't see statistical results any time soon.

[Anon2014 in reply to mypk]

I suspected as much but wanted to check HU just in case someone did have something they could point me to.

[ellie2211 in reply to mypk]

My dad was on this trial. He is off it now due to side effects. He had some positive results but had severe pain/infections from the drug. It doesn't happen in all patients as far as I know.

[Anon2014 in reply to ellie2211]

thanks so much for your help. Sorry it didn’t work out for your father. Did they give him any clue as to the percentage of participants who left the trial or percentage who had positive results?

[ellie2211 in reply to Anon2014]

I think AMG 509 did work out for him despite the side effects he saw a big drop in his PSA. They didn't give him an idea. But his doctor said he was one of the most responsive.

[Seasid]

I myself would not even consider any phase I clinical trials until I ran out of standard of care options.

We can of course learn and follow what is happening but that is it.

I am just curious what made you to consider phase I trials, in particular this one?

[Anon2014 in reply to Seasid]

I understand your sentiment about phase 1 trials and even turned down one a year ago. I’m getting close to exhausting SOC and asked my oncologist to pull together a treatment plan that would run me through to end stage. He suggested I meet with a Dr/researcher in Nashville about trials first. The researcher reviewed my records and recommended the AMG 340 trial. The problem with exhausting all SOC options first is that may exclude one from some trials. I’ve seen where being treated with more than one chemotherapy drug is sometimes in the exclusion criteria.

[Seasid in reply to Anon2014]

I agree. It is not simple to make a decision. Still standard of care is still better than the unknown phase I experiment. Sadly.

[Seasid]

I will wait for preliminary data before embarking in these studies. They have risks as indicated in the preliminary results of AMG 160

investors.amgen.com/static-...

There is no data about effectivity. Does it control the cancer? For how long? etc. etc.

They should have some preliminary data, if they have not presented in one of the recent meetings, make you think what is going on with this treatment.

This is only my way of thinking about AMG 509. I was interested but that's it.

[Anon2014 in reply to Seasid]

I asked the researcher about the effectiveness thus far, he said they’ve had some success but didn’t have any results/statistics. He did say there was a risk of CRS (cytokine release syndrome) but that he’s not lost any patients.

[mypk in reply to Anon2014]

The AMG 340 trial uses a different BiTE module than the AMG 160 trial. AMG 160 used Acapatamab, a HLE BiTE molecule targeting PSMA for the treatment of patients with mCRPC, which was dropped in favor of AMG 340. See:

fiercebiotech.com/biotech/a...

So adverse effects should be less than those listed in this report on AMG 160:

urotoday.com/conference-hig...

Concerning my own case, I've nearly reached the end of SOC therapies too after Cabazitaxel failed and therefore applied for the AMG 509 trial last week. I see it as one additional chance. 😀

[Spyder54 in reply to mypk]

you say you have run out of SOC. Have you had Provenge? My Onco says he has many mHRPCa patients now past 5 yrs and doing well. He stressed early is better when PSA below 10 but rising. Stressed to me to get right on it.

Mike

[mypk in reply to Spyder54]

Provenge is not available in Europe.

On May 6, 2015, at the request of the marketing authorization holder, the European Commission withdrew the marketing authorization with effect from June 30, 2015. The withdrawal from the market is seen in connection with the benefit assessment by the Institute for Quality and Efficiency in Health Care (IQWiG), which had initially certified no additional benefit for the preparation, but after correction only a "non-quantifiable additional benefit." The assessments of IQWiG and the Federal Joint Committee (G-BA) are decisive for the pricing of a drug.

...................

A short extract (machine translated) from the resolution of the Federal Joint Committee on an amendment to the German Medicines Directive, 19 March 2015 (The complete document is 16 pages long):

PFS

For all 3 studies, the study documents indicate that no statistically significant difference in disease progression was seen in either study arm. Median time to progression (in months, intervention vs. control): 3.4 vs. 3.3 (IMPACT), 2.7 vs. 2.3 (D9901), 2.5 vs. 2.3 (D9902A). Hazard ratios (with 95%- Confidence intervals): 0.94 (0.77; 1.15) (IMPACT); 1.45 (0.99; 2.11) (D9901); 1.09 (0.69; 1.70) (D9902A). An additional benefit of sipuleucel-T compared to the appropriate comparator therapy (wait-and-see approach) is therefore not proven for this endpoint.

CONCLUSIONS:

For patients with asymptomatic or minimally symptomatic, metastatic (non-visceral), castration-resistant prostate cancer, in whom chemotherapy is not yet clinically indicated, there is a non-quantifiable additional benefit for sipuleucel-T compared to the wait-and-see approach in the overall analysis of the available results on mortality, morbidity, and adverse events. Due to the uncertainties in the study design, the extent of the additional benefit with regard to the results in the endpoint mortality cannot be quantified.

.......................

According to the above, maybe there is a benefit for mHRPCa patients, but most benefit seems to go to those selling it in form of dollars. 😆

[Seasid in reply to Spyder54]

My MO was not overly enthusiastic about Provenge saying that it doesn't lower PSA.

He would not have anything against Provenge, but he said that I would need to come up with 120k $ in order to organise it in LA. At this moment I don't have that money to spend on Provenge.

I am polymetastatic and already 5 years since diagnosed on Degarelix alone with early chemotherapy, early 4 X Ga68 PSMA Pet scan and recently I SBRT my prostate with CRPC in it.

I would be happy to get Provenge as I believe (my delusional thinking maybe) that provenge is effective against prostate CSCs and that could be a reason that it doesn't lower the PSA but extends life.

[ellie2211 in reply to mypk]

I hope you get good results!

[mypk in reply to Seasid]

Initial data readout is anticipated in H2 2023 for AMG-509

[Anon2014 in reply to mypk]

Is AMG 509 in phase 1 or 2? How is it different than AMG 340? Let me know when you get the initial data readout on it?

[mypk in reply to Anon2014]

AMG 340 binds to the PSMA (Prostata Specific Membran Antigen)

AMG 509 binds to the STEAP1 (Six Transmembrane Epithelial Antigen of the Prostate 1)

For more details check: amgenoncology.com/all-resou...

Concerning the initial data readout of AMG-509 (now renamed to Xaluritamig) I assume an abstract will be published at amgen.com/newsroom, or maybe presented at the ESMO congress 2023. Like AMG-340 (for which there is no study location in my country) it is also a phase one trial. You may follow any changes in a selected trial on clinicaltrials.gov if you click the 'Historical Changes' link.

[Anon2014 in reply to mypk]

ok, thanks

[mypk]

It just came into my mind that (if I understand it correctly) there is a clinical trial going on in Germany, which appears to be very similar to the AMG-340 study:

clinicaltrials.gov/ct2/show...

Contrary to the status currently shown on clinicaltrials.gov this study is not recruiting anymore, because they already enrolled the wanted 86 participants. However, they published their findings from the dose escalation phase already:

.....................

Results of the first study phase (dose escalation study).

CC-1 is used in patients with castration-resistant, metastatic prostate cancer. In the first study phase, first signs of therapeutic activity were observed with good tolerability.

A total of 14 patients were included in the dose escalation phase. These received at least one treatment with CC-1. As expected, a non-specific activation of the immune system, the so-called cytokine release syndrome (CRS), was observed in almost all study participants. However, this activation was mild and temporary. The target dose of CC-1 aimed for in the study design could already be defined after the treatment of only eight patients. "With very good tolerability of CC-1, some patients were treated more than once, as a decrease in the tumor marker PSA was already observed after the first cycle," said Prof. Helmut Salih, head of the clinical trial. "These results are very encouraging for us and we hope that we will be able to prove the efficacy of our antibody in the dose expansion part that is starting now."

.......................

I might be wrong, but I would expect something similar with AMG-340.

[Anon2014 in reply to mypk]

thanks, they do appear similar.