LBA40_PR - TARGET: A randomized, phase II trial comparing vintafolide versus vintafolide plus docetaxel, versus docetaxel alone in second-line treatment of fo...

Date 27 September 2014
Event ESMO 2014
Session NSCLC, metastatic 1
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Rohit Lal
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors N. Hanna1, E. Juhász2, C. Cainap3, O.A. Gladkov4, R. Ramlau5, O. Juan-Vidal6, R. Lal7, J. Symanowski8, W. Perez9, B. Nguyen10, W. Harb11
  • 1Department Of Medicine, Indiana University, 46202 - Indianapolis/US
  • 2I And Xiv, Koranyi National Institute of TB and Pulmonology, Budapest/HU
  • 3Medical Oncology, Institute of Oncology Cluj, Cluj Napoca/RO
  • 4Chemotherapy, Chelyabinsk Regional Clinical Oncology Dispensary, Chelyabinsk/RU
  • 5Oncology, Poznan University of Medical Science, Poznan/PL
  • 6Medical Oncology, Hospital Universitari La Fe, Valencia/ES
  • 7Medical Oncology, Guy’s & St Thomas’ NHS Foundation Trust, London/GB
  • 8Cancer Biostatistics, Levine Cancer Institute, Charlotte, Charlotte/US
  • 9Clinical Operations, Endocyte, Inc., West Lafayette/US
  • 10Medical Affairs, Endocyte, Inc., West Lafayette/US
  • 11Oncology Center, Horizon, Lafayette/US

 

Abstract

Aim

The folate receptor (FR) is expressed in many epithelial cancers, including NSCLC, and may be a useful biomarker for therapy selection. Vintafolide, a folate-vinca alkaloid drug conjugate, is a FR-targeted drug. Its companion imaging agent, 99mTc-etarfolatide, enables non-invasive imaging of FR expression. The TARGET study (NCT01577654) assessed the benefit of FR-targeted therapy in 199 second-line NSCLC patients with all target lesions expressing FR [FR(100%)].

Methods

Patients were randomized 1:1:1 to vintafolide, vintafolide + docetaxel (DTX), or DTX alone. Vintafolide (2.5 mg) was administered on D1, 4, 8, and 11 and DTX (75 mg/m2) on D1 of a 3-week cycle. The primary endpoint was PFS; secondary endpoints included OS and ORR. The significance level of each PFS and OS analysis was one-sided alpha = 0.10 with no multiple testing adjustments.

Results

Vintafolide Vinta + DTX DTX

All patients

ORR

Median PFS (months, 95% Cl)

PFS HR (vs. DTX; 95% Cl)*

1-sided p-value

Median OS (months, 95% Cl)

OS HR (vs. DTX; 95% Cl)*

1-sided p-value

N=63

6%

1.6 (1.4; 3.2)

1.35 (0.92; 1.96)

0.9421

8.4 (5.6; 12.3)

1.05 (0.68; 1.61)

0.5818

N=68

22%

4.2 (2.8; 5.4)

0.75 (0.52; 1.09)

0.0696

11.5 (7.3; 13.4)

0.88 (0.58; 1.36)

0.2874

N=68

13%

3.3 (1.72; 4.2)

-

-

8.8 (5.4; 12.6)

-

-

Adenocarcinoma patients

ORR

Median PFS (months, 95% Cl)

PFS HR (vs. DTX; 95% Cl)*

1-sided p-value

Median OS (months, 95% Cl)

OR HR (vs. DTX; 95% Cl)*

1-sided p-value

N=41

5%

1.6 (1.4; 3.3)

1.40 (0.88; 2.24)

0.9247

8.4 (5.1; 12.5)

1.00 (0.59; 1.71

0.4957

N=43

21%

4.2 (2.6; 5.4)

0.73 (0.46; 1.16)

0.0899

12.5 (8.1; - )

0.70 (0.40; 1.22)

0.1018

N=49

14%

3.0 (1.6; 4.2)

-

-

6.6 (4.8; 12.9)

-

-

* Unstratified Cox model.

With the pre-specified stratified analysis adjusting for baseline factors (time since last chemotherapy, best response and stage), the OS HR for vintafolide+DTX vs. DTX were 0.75 (1-sided p=0.1066) for all patients, and 0.51 (1-sided p=0.0147) for the predefined adenocarcinoma patient subgroup.

Conclusions

Vintafolide+DTX showed clinically meaningful improvement across all efficacy endpoints (ORR, PFS and OS) over single-agent DTX, with the largest benefit observed in the adenocarcinoma subgroup.

Disclosure

J. Symanowski: Other substantive relationships: Consultant for Endocyte, Inc.; W. Perez: Other substantive relationships: Employee of Endocyte, Inc.; W. Harb: Corporate-sponsored research: Endocyte sponsored participation in EC1456 study. All other authors have declared no conflicts of interest.