First clinical trial of Lu-177-PSMA-617 in recurrent, hormone-sensitive men

While we expect only a few months of extra survival from the VISION trial of Lu-177-PSMA-617 in heavily pretreated, metastatic, castration-resistant men (see this link), we hope to get more out of the radiopharmaceutical if used earlier. Privé et al. reported the results of a pilot trial in 10 recurrent men treated with Lu-177-PSMA-617 at Radboud University in Nijmegen, The Netherlands. They were all:

• Recurrent after prostatectomy ± salvage radiation (PSA>0.2 ng/ml) 
• Rapid PSA doubling time (< 6 months)
• Between 1-10 metastases detectable on a PSMA PET scan or USPIO MRI
• At least 1 metastasis > 1 cm.
• Unable to receive SBRT to metastases 
• No visceral metastases 
• Have not begun salvage ADT
• Treated with a low dose (3 GBq) on day 1; second treatment (~6 GBq) after 8 weeks (compared to dose in VISION trial of 7.4 GBq in each of 4-6 cycles)

After 24 weeks of follow-up after Cycle 2:

• 5 patients had PSA reduced by >50% (1 undetectable)
• 2 patients had stable PSA
• 3 patients had PSA progression
• 6 patients had a radiographic response
• 4 patients had radiographic progression
• ADT-deferred survival was 9.5 months (median)
• Those with lymph node only metastases had the best response
• Those with any bone metastases had lesser response

After 2nd dose, comparing their 24-week PSA to their 12-week PSA:

• PSA was continuing to decline in 3 patients
• PSA was rising again in 6 patients

Side effects were mild (no grade 3) and transient:

• fatigue in 7; nausea in 3
• dry mouth (xerostomia) in 2

There are lots more questions than answers:

• Would a higher dose and more treatments be more effective?
• Would a higher dose and more treatments be more toxic?
• Is it like Xofigo in that it's more effective with micrometatases? If so, would a combination with SBRT targeted at the larger metastases be more effective?
• Since it was more effective on lymph nodes, would it make a good combination with Xofigo for patients who have both lymph node and bone metastases? (See also Th-227-PSMA)
• Because there seems to be a continued abscopal effect for some patients, would combining it with Provenge be optimal?
• Would pretreatment with ADT or a new anti-androgen (Xtandi, Erleada or Nubeqa) increase expression of PSMA, and increase radiosensitivity?
• Can we predict who will benefit?
• Use in other patient populations remains to be explored: high-risk, newly diagnosed metastatic, castration-resistant but chemo-naive. Optimal sequencing with other therapies remains to be explored.

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
Lu-177-PSMA-617  LuCarbo	Carboplatin		Not yet recruiting	Dana-Farber, Boston
Lu-rhPSMA-10.1		•Recurrent postRP •regionally positive on PSMA PET	recruiting	Emory,  Atlanta
Lu-177-JH20002		•Advanced PCa	recruiting	•California •Florida •Michigan
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	recruiting	TBD
Lu-177-PNT2002 LUNAR	Before SBRT	Recurrent and oligometastatic	recruiting	UCLA
Ac-225-J591 ACTION	SBRT, ADT if polymetastatic	Recurrent # mets	recruiting	Weill Cornell
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	• 56 locations
Ac-225-PSMA-I&T TATCIST			Recruiting	• Houston
Ac-225-J591			recruiting	• Weill Cornell • Brooklyn Methodist
Pluvicto+ONC392 (a CTL4 blocking immunotherapy)			recruiting	• NYU Langone • Columbia
Ac-225-J591 + Lu-177-PSMA- I&T			recruiting	• 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	• 174  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