Details of data from Prostate cancer clinical trials

Investigated (inv)

Comparator (comp)

Lu-PSMA-617

SoC

551

280

Phase:

3

Randomisation:

Open label

Primary tumour:

Prostate

Subtype (biomarker):

mCRPC

Stage:

Line of therapy:

L3

Primary

Lu-PSMA-617

SoC

HR

p

rPFS

8.7 mo

3.4 mo

0.40 (0.29-0.57)

<0.001

OS ITT

15.3 mo

11.3 mo

0.62 (0.52-0.74)

<0.001

Secondaries

Lu-PSMA-617

SoC

HR

p

TFSE

11.5 mo

6.8 mo

0.50 (0.40-0.62)

<0.001

ORR

29.8%

1.7%

24.99 (6.05-103.24)

<0.001

≥ 50% PSA decreases

46.0%

7.1%

11.19 (6.25-20.04)

na

≥ 80% PSA decreases

33.0%

2.0%

23.62 (8.57-65.11)

na

(all grades, %)

Lu-PSMA-617

SoC

p

Fatigue

43.1

22.9 NA

Dry mouth

38.8

0.5 NA

Nausea

35.3

16.6 NA

Anemia (grade ≥3)

12.9

4.9 NA

Thrombocytopenia

17.2

4.4 NA

Lymphopenia

14.2

3.9 NA

AE that led to reduction in Lu-PSMA

5.7 —

—

AE that led to interruption of Lu-PSMA

16.1 —

—

AE that led to discontinuation of Lu-PSMA

11.9 —

—

AE that led to death

3.6

2.9 NA

—

Inclusion
Exclusion

- Patients must have the ability to understand and sign an approved informed consent form (ICF).dc-return- Patients must have the ability to understand and comply with all protocol requirements.dc-return- Patients must be ≥18 years of age.dc-return- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.dc-return- Patients must have a life expectancy >6 months.dc-return- Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.dc-return- Patients must be 68Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive, and eligible as determined by the sponsor's central reader.dc-return- Patients must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L).dc-return- Patients must have received at least one NAAD (such as enzalutamide and/or abiraterone).dc-return- Patients must have been previously treated with at least 1, but no more

- Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed.dc-return- Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to day of randomization.dc-return- Any investigational agents within 28 days prior to day of randomization.dc-return- Known hypersensitivity to the components of the study therapy or its analogs.dc-return- Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.dc-return- Transfusion for the sole purpose of making a subject eligible for study inclusion.dc-return- Patients with a history of Central Nervous System (CNS) metastases must have received therapy (surgery, radiotherapy, gamma

Characteristics

Lu-PSMA-617

SoC

Age

Median age (range)dc-comma yr

71.0 (52–94)

72.0 (51–89)

—

ECOG

0 or 1

91.4%

91.3%

—

Site of disease

Lung

9.1%

10.2%

Liver

12.2%

13.3%

Lymph node

50.1%

50.5%

Bone

91.2%

91.3%

PSA level

Median PSA level (range) — ng/ml

93.2 (0–6988)

90.7 (0–6600)

—

Alkaline phosphatase level

Median alkaline phosphatase level (range) — IU/liter

108.0 (26–2524)

96.0 (34–1355)

—

LDH level

Median LDH (range) — IU/liter

230.5 (119–5387)

232.0 (105–2693)

—

Gleason score at diagnosis

8 - 10

58.7%

60.2%

Unknown

7.3%

9.7%

—

Prostatectomy

Previous prostatectomy

41.3%

41.8%

—

Previous androgen-receptor–pathw

One regimen

55.3%

50.0%

Two regimens

39.0%

43.9%

More than two regimens

5.7%

6.1%

—

Previous taxane therapy

One regimen

53.8%

52.0%

Two regimens

44.9%

46.9%

Docetaxel

97.9%

97.4%

Cabazitaxel

41.8%

42.9%

—

Ad-hoc:

no.pts inv.

no.pts comp.

Lu-PSMA-617

SoC

HR

p

rPFS ITT

551

280 8.8 mo

3.6 mo

0.43 (0.32-0.58)

na

OS

240

129 14.6 mo

10.4 mo

0.63 (0.51-0.79)

na

—

rPFS
OS ITT

analisys of rPFS

Lu-PSMA-617

SoC

HR (95% CI)

Use of androgen receptor pathway inhibitors

Yes

—

0.53 (0.37-0.76)

No

—

0.27 (0.19-0.39)

LDH

≤260 IU/L

—

0.44 (0.32-0.61)

>260 IU/L

—

0.37 (0.25-0.53)

Liver metastases

Yes

—

0.28 (0.15-0.53)

No

—

0.43 (0.33-0.57)

ECOG score

0 or 1

—

0.43 (0.33-0.56)

2 —

—

0.18 (0.08-0.38)

Age

<65 yr

—

0.42 (0.23-0.76)

≥65 yr

—

0.40 (0.30-0.53)

Race

White

—

0.38 (0.29-0.50)

African Maerican or Black

—

0.72 (0.23-2.20)

—

analisys of OS ITT

Lu-PSMA-617

SoC

HR (95% CI)

Use of androgen receptor pathway inhibitors

Yes

—

0.54 (0.41-0.70)

No

—

0.68 (0.53-0.87)

LDH

≤260 IU/L

—

0.63 (0.50-0.80)

>260 IU/L

—

0.63 (0.48-0.84)

Liver metastases

Yes

—

0.87 (0.53-1.43)

No

—

0.62 (0.51-0.76)

ECOG score

0 or 1

—

0.61 (0.50-0.74)

2 —

—

0.63 (0.35-1.13)

Age

<65 yr

—

0.73 (0.49-1.10)

≥65 yr

—

0.59 (0.48-0.73)

Race

White

—

0.63 (0.52-0.77)

African America or Black

—

0.60 (0.29-1.24)

—

Prostate cancer: VISION trial

EMA SPC links

2021-09-16

O. Sartor

Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer

Investigated (inv)

Comparator (comp)

Randomisation:

Primary tumour:

Subtype (biomarker):

Stage:

Line of therapy:

Primary

Lu-PSMA-617

SoC

HR

p

rPFS

8.7 mo

3.4 mo

0.40 (0.29-0.57)

<0.001

OS ITT

15.3 mo

11.3 mo

0.62 (0.52-0.74)

<0.001

Secondaries

Lu-PSMA-617

SoC

HR

p

TFSE

11.5 mo

6.8 mo

0.50 (0.40-0.62)

<0.001

ORR

29.8%

1.7%

24.99 (6.05-103.24)

<0.001

≥ 50% PSA decreases

46.0%

7.1%

11.19 (6.25-20.04)

na

≥ 80% PSA decreases

33.0%

2.0%

23.62 (8.57-65.11)

na

(all grades, %)

Lu-PSMA-617

SoC

p

Fatigue

43.1

22.9

NA

Dry mouth

38.8

0.5

NA

Nausea

35.3

16.6

NA

Anemia (grade ≥3)

12.9

4.9

NA

Thrombocytopenia

17.2

4.4

NA

Lymphopenia

14.2

3.9

NA