Showing posts with label clinical trial. Show all posts
Showing posts with label clinical trial. Show all posts

Tuesday, August 11, 2020

PSMA-targeted radiopharmaceutical clinical trials in the US

(frequently updated)

Now that the VISION trial of Lu-177-PSMA-617 is no longer recruiting, some patients are wondering if they can still get PSMA-targeted radiopharmaceuticals in the US, without traveling to Germany, Australia, India, etc. Here is a list of trials that are active, still open to recruitment, or will soon be recruiting. 

Unless otherwise noted, they are all for men who are: 

  • metastatic
  • castration-resistant 
  • have had at least one taxane chemotherapy
  • at least one of the advanced androgen receptor therapies (e.g., Zytiga, Xtandi, Erleada, or Nubeqa)
  • no Xofigo
  • PSMA-avid on a PSMA PET/CT scan

Radiopharmaceutical

Adjuvant drugs

Extra criteria

Recruitment status/ contact

Locations

Ac-225-PSMA-R2


•After or without prior Lu-177-PSMA

Begins 10/23

TBD

Lu-177-PSMA-617

PSMACare

1. ADT

2.ARSi+ADT (ARSi=Zytiga, Xtandi,Erleada or Nubeqa)

•Metastatic with PSMA PET, but not with conventional imaging

•CRPC

•No prior ARSi or chemo

Begins 12/23

TBD

Lu-177-PNT2002

LUNAR

Before SBRT

Recurrent and oligometastatic

recruiting

UCLA


Lu-177-rhPSMA-10.1


±previous chemo

recruiting 

•Maryland

•St.Louis

•Omaha

•Mt Sinai-NYC

Lu-177-PSMA-I&T


Chemo naïve, failed one hormonal

recruiting

• 58 locations

Ac-225-PSMA-I&T

TATCIST



Recruiting

• Houston

Ac-225-J591

 

 

recruiting

• Weill Cornell

• Brooklyn Methodist

Pluvicto+ONC392 (a CTL4 blocking immunotherapy)



Begins 9/23

• NYU Langone

• Columbia

• Maryland

• Omaha

• Duke

• UTSW (Dallas)

•UWisc. Carbone

Ac-225-J591 + Lu-177-PSMA- I&T

 


Suspended

• Weill Cornell

• Brooklyn Methodist

Ac-225-J591

Keytruda

No chemo since castration resistant

recruiting

• Weill Cornell

• Brooklyn Methodist

• Dana Farber

• Columbia

Cu-67-SAR-bisPSMA

SECuRE

 

Previous chemo OK, not required

recruiting

• Johns Hopkins

•Mayo Rochester

•Mayo, AZ

•Tulane, N.O.

•Barnes Jewish, St. Louis

•Omaha, NE

•Weill Cornell

Lu-177-PSMA-617

PSMAddition


mHSPC

(M1 or N1)

Treatment naive

Recruiting

• 188 sites

Lu-177-PSMA-617

Keytruda

No chemo since castration resistant

active, not recruiting

UCSF

Lu-177-CTT1403

 

No Jevtana

active, not recruiting

UCSF

Lu-177-PSMA-617

 

 

Active, not recruiting

•Weill Cornell

•Tulane

Th-227-Antibody

(see article)

 

 

active, not recruiting

• Royal Marsden (UK)

• Finland

• Tulane

• MSK

• Omaha, NE

Lu-177-J591

Ketoconazole

Prior RP or RT

CRPC

Non-metastatic

active, not recruiting

• Weill Cornell

• USC

• Georgetown

• IU

• U of Iowa

• UPMC

Lu-177-PSMA-R2

 

 

Active, not recruiting

• Stanford

• Yale

• Tulane

• Johns Hopkins

• Mt Sinai

• MD Anderson

• U of Wisconsin

• Phoenix

Lu-177-PSMA-617

PSMAfore

 

Chemo and immunotherapy naïve, failed one hormonal

Active, not recruiting

(Phase 3 RCT)

• 72  sites

Lu-177-PSMA-617

(VISION)

 

 

Active, not recruiting

• 84 locations

Results expected August 2020

I-131-1095-MIPS

(see article)

Xtandi

Chemo naïve

Failed Zytiga

Active, not recruiting

• 17 locations

Results expected December 2021



Tuesday, October 30, 2018

Newest radiopharmaceutical: Th-227-PSMA-antibody

Bayer has announced a new clinical trial of the latest entry in the race for radiopharmaceuticals to treat prostate cancer, joining Lu-177-PSMA-617, Ac-225-PSMA-617, and I-131-MIP-1095. They are trying Thorium-227 attached to a PSMA antibody.

Thorium-227, like Ac-225, is an alpha-particle emitter. Alpha emitters are very powerful, but very short range, only killing cells that are 2 to 10 cells away from the cancer cell it attaches to. This may limit its toxicity, but may require higher doses for larger, more widespread tumors.  Beta emitters, like Lu-177, are less powerful, but the beta particle penetrates to a much greater depth, affecting about 125 cells. Researchers at the University of Heidelberg are experimenting with mixtures of the two.

The other part of the equation is the ligand that the radioactive atom is attached to and that attaches to the PSMA protein on the prostate cancer cell. Ligands include PSMA-617, PSMA-I&T, MIP-1095, and J591. Ligands may be small molecules, antibodies, or "minibodies." Bayer is using a proprietary antibody-type ligand that they developed for the purpose. Ligands that are more specific for PSMA have less toxicity.

On the other side of the ligand molecule, it must bind very tightly to the radioactive element. If it doesn't, the radioactive element might be released into systemic circulation where it can damage healthy cells. Heavy metals, like thorium, are attached relatively weakly by a process called "chelation," but some chelators are stronger than others. Researchers have so far been unsuccessful in developing a stable chelate for Ra-223 (the main ingredient in Xofigo, which is also manufactured by Bayer) to a PSMA ligand. However, Th-227 decays into Ra-223, so it is unknown if the thorium chelate will continue to hold as it decays. However, Bayer has already begun two clinical trials for Th-227 chelated to an antibody for non-Hodgkin's lymphoma since 2015, and for ovarian cancer and mesothelioma since April, which have not been terminated for excess toxicity. There is every reason to hope that the chelation complex they devised for the PSMA-antibody ligand holds up in biological systems. But if it doesn't hold chemically, it becomes the active ingredient in Xofigo, and may be doubly therapeutic in men with bone metastases.

This is a dose-finding (Phase 1) clinical trial among 108 patients with metastatic castration-resistant prostate cancer. They list 4 locations that will be recruiting: Memorial Sloan Kettering in NYC, Tulane (New Orleans), as well as locations in the UK and Finland.

Thursday, October 11, 2018

I-131-MIP-1095 has entered a phase 2 randomized clinical trial

As I reported last year, a new radiopharmaceutical has entered the pack. I-131-MIP-1095, a powerful beta-particle emitter attached to a PSMA-targeted ligand, will enter a multicenter phase 2 randomized clinical trial. Progenics®, the manufacturer, put out a press release, which can be read here. (Update 4/2020) The clinical trial has begun recruiting in 17 locations in the US and Canada.

They will be testing a combination of I-131-MIP-1095 with enzalutamide (Xtandi) in patients who are metastatic, castration resistant, have not yet had chemotherapy, and who have become resistant to Zytiga. It is hoped that Xtandi will radiosensitize the cancer to the radiopharmaceutical with a resultant PSA decrease.

175 evaluable patients will be recruited; half will get the radiopharmaceutical + Xtandi, half will get Xtandi alone. All patients will be screened using DCFPyL PET/CT to assure that their metastases are PSMA-avid. The primary endpoint - the percent who have greater than 50% PSA reduction - will be collected for a year. Secondary endpoints - radiographic response, progression-free survival, and overall survival - will be reported at the end of two years.

Another radiopharmaceutical in clinical trials is Lu-177-PSMA-617 .  There are various phase 1 and 2 clinical trials in the US and internationally (see list at the end of this link).

I recently reported about the very promising outcomes of Ac-225-PSMA-617 in Germany. Patients report that they are combining Ac-225-PSMA-617 and Lu-177-PSMA-617 to get the advantages of each. Weill Cornell in NYC is investigating Ac-225-J591 in a phase 1 trial.

For information on the trial of Th-227-PSMA, see this link.