AMG 509 clinical trial

[Coop68]

Does anyone here have any info about or perhaps have participated in the Phase I clinical trial of AMG 509? Thank you.

[pjoshea13]

clinicaltrials.gov/ct2/show...

ascopubs.org/doi/abs/10.120...

Phase I study of AMG 509, a STEAP1 x CD3 T cell-recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC).

W. Kevin Kelly, Daniel Costin Danila, William Jeffery Edenfield, Rahul Raj Aggarwal, Daniel Peter Petrylak, A. Oliver Sartor, Christopher Joseph Sumey, Tanya B. Dorff, Evan Y. Yu, Nabil Adra, David Michael Waterhouse, Andrew J. Armstrong, Lisa Horvath, David William Pook, Leonard Joseph Appleman, Aubrey Lau, Mark Salvati, Hosein Kouros-Mehr

Thomas Jefferson University, Philadelphia, PA; Memorial Sloan Kettering Cancer Center, New York, NY; Prisma Health Greenville Memorial Hospital, Greenville, SC; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Yale Cancer Center, New Haven, CT; Tulane Cancer Center, New Orleans, LA; Sanford Cancer Center, Sioux Falls, SD; City of Hope, Duarte, CA; University of Washington, Seattle, WA; Indiana University School of Medicine, Indianapolis, IN; OHC (Oncology Hematology Care), Inc., Cincinnati, OH; Duke University School of Medicine, Durham, NC; Chris O'Brien Lifehouse, Camperdown, NSW, Australia; Monash University, Melbourne, VIC, Australia; UPMC Hillman Cancer Center, Pittsburgh, PA; Amgen Inc., Thousand Oaks, CA

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Abstract Disclosures

Abstract

TPS5589

Background: Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a cell surface antigen that is highly expressed in prostate cancer. AMG 509 is a potent bispecific XmAb 2+1 immune therapy designed to direct T-effector cells to STEAP1-expressing cells. AMG 509 contains two identical humanized anti-STEAP1 Fab domains that bind STEAP1-expressing cells, an anti-CD3 scFv domain that binds T cells, and an Fc domain, engineered to lack effector function, that extends serum half-life. In preclinical studies, AMG 509 induced potent and specific T-cell-mediated lysis of STEAP1-expressing cancer models. Methods: This open-label, phase I, first-in-human study will evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 509 in patients with relapsed/refractory mCRPC. The dose exploration phase (n=40) will estimate the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) using a Bayesian logistic regression model. The dose expansion phase (n=30) will confirm safety, PK, and pharmacodynamics at the MTD or RP2D and collect further safety, efficacy, and biomarker data. Efficacy will be assessed by prostate-specific antigen response, circulating tumor cell response, and objective tumor response per RECIST 1.1 with Prostate Cancer Working Group 3 modifications. Key inclusion criteria: men ≥18 years with histologically/cytologically confirmed mCRPC who are refractory to novel hormonal therapy (e.g., abiraterone and/or enzalutamide) and have failed 1–2 taxane regimens or are medically unsuitable for or have refused taxanes; ongoing castration with total serum testosterone ≤50 ng/dL; evidence of progressive disease; ECOG performance status 0–1; life expectancy ≥3 months; and adequate hematologic, renal, hepatic, and cardiac function. In the dose exploration phase, novel antiandrogen therapy must have been given in the metastatic setting. Key exclusion criteria: pure small-cell or neuroendocrine carcinoma of the prostate; untreated CNS metastases or leptomeningeal disease; any anticancer therapy or immunotherapy, radiation therapy, or major surgery <4 weeks from first dose; history of or current autoimmune disease or any disease requiring immunosuppressive therapy (≤10 mg/d prednisone permitted); prior STEAP1-targeted therapy; infection requiring IV antimicrobials <7 days from first dose. The study opened in January 2020 and is recruiting patients. Clinical trial information: NCT04221542.

© 2020 American Society of Clinical Oncology

-Patrick

[Coop68 in reply to pjoshea13]

Thank you for your reply. I was also wondering if any of the members here had participated in the clinical trial. My husband has been offered a spot, but the possible side effects are terrifying.

[tango65]

Some info:

cancerres.aacrjournals.org/...

targetedonc.com/view/novel-...

[Coop68 in reply to tango65]

Thank you!

[tango65 in reply to Coop68]

Best of luck.

[Tall_Allen]

I would be very surprised if you found anyone on it on this forum - there are only 110 men who will be recruited for it nationwide, and it's only started recruiting last year. If you want to get a sense of side effects, ask the investigator, but remember it's a dose escalation study, so the side effects someone else experiences probably will NOT be from the dose that he will be receiving.

AMG 509 is a kind of medicine from the class of experimental medications that Amgen is developing called BiTEs (bispecific T-cell engagers). In this case, one part of the molecule seeks out a protein on the prostate cancer cell surface called STEAP1. The other part of the molecule attracts T-cells to it. The T cells kill the cancer cell. Amgen is trying several BiTEs - some attach to other prostate cancer cell surface proteins like PSMA. It's too early to tell if it is effective but we are all very hopeful.

[Coop68 in reply to Tall_Allen]

Thank you, TA.

[Magnus1964]

the AMG 509 is in a phase I trial. It may take a long time to reach phase III. that would be the trial to look for.

[Coop68]

How long have you been on it?

[Coop68]

What was your PSA when you started?

[Coop68]

Fantastic. My husband is in the process of being screened at MSK to begin AMG-509. He was told he would have to be admitted for two nights each for the first four weeks, after which it would be administered on an outpatient basis. Was that your experience?

[Coop68]

Thank you for the info!

[pier21]

Hi Coop,My father is starting AMG509 study next week at Hillman cancer center. He is 80 years old and has refused chemotherapy. I will post updates on his progress in the near future.

[Coop68 in reply to pier21]

Hope your dad does well! My husband begins the trial next Tuesday at MSK. I will post updates as well. Thank you.

[pier21]

Hi Coop, my dad has had 2 infusions so far. Some stomach burning and low grade fever, but oncologist is not concerned as his symptoms are mild. No scan information until January. Ill let you know what his PSA is once they take it. Orherwise he is in great spirits, and we are hoping for the best.

[Coop68 in reply to pier21]

Hi, there -Glad your dad is doing well. Unfortunately, at the last minute, my husband was not accepted into the Amgen 509 clinical trial; however, he has been accepted into another clinical trial (P-PSMA-101) at MSK. He goes on Monday to have his "T" cells extracted, then they are sent out to be "powered up," a process that takes approx. 6 weeks. Then the "T" cells are put back into the body. Please keep me posted on how your dad is doing.

[lewicki in reply to pier21]

How is dad doing and is he still on the trial. Thanks

[pier21 in reply to lewicki]

Hi Lewicki,

Unfortunately it did not work for him. We are moving in a different direction. He is having a PSMA PET on April 5th. We have 3 other options available. LU 177, cabazitaxel, and AMG160. We will make a decision after PSMA Pet.

[pier21]

Thats another extremely promising trial! I wish him the best.

[FightforDad09]

Hello! So great to hear about your journey so far in this trial. Can I ask where you have your treatments?