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509TiP LUX-LUNG 8: A RANDOMIZED, OPEN-LABEL, PHASE III
TRIAL OF AFATINIB VS. ERLOTINIB IN PATIENTS WITH
ADVANCED SQUAMOUS CELL CARCINOMA OF THE LUNG
AS SECOND-LINE THERAPY FOLLOWING FIRST-LINE
PLATINUM-BASED CHEMOTHERAPY
G. Goss 1 ,S.Lu 2 , E. Felip 3 , A. Ardizzoni 4 , V. Georgoulias 5 , S. Gadgeel 6 ,
V. Chand 7 ,Y.Gu 7 , Y.S. Olivo 8 , J. Soria 9
1 Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON, CANADA,
2 Shanghai Lung Tumor Clinical Center, Shanghai Chest Hospital, Shanghai,
CHINA, 3 Oncology, Vall d’Hebron University Hospital, Barcelona, SPAIN,
4 Onco-hematology Department of Internal Medicine, A.O. Universitaria di Parma,
Parma, ITALY, 5 Medical Oncology, University Hospital of Heraklion, Heraklion,
GREECE, 6 Medical Oncology, Karmanos Cancer Center, Detroit, MI, UNITED
STATES OF AMERICA, 7 Clinical Development - Oncology, Boehringer Ingelheim
Pharmaceuticals, Inc., Ridgefield, CT, UNITED STATES OF AMERICA, 8 Clinical
Trial Management, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT,
UNITED STATES OF AMERICA, 9 Dept. of Medicine, Institut de Cancérologie
Gustave Roussy, Villejuif Cedex, FRANCE
Background: Patients with advanced squamous cell carcinoma (SCC) of the lung
have limited treatment options. Although treatment with the EGFR tyrosine kinase
inhibitor erlotinib is indicated in the second- or third-line or maintenance setting,
the benefit is limited. Afatinib is a novel, selective, orally bioavailable, ErbB family
blocker, irreversibly blocking EGFR (ErbB1), HER2 (ErbB2) and HER4 (ErbB4).
Based on its promising preclinical profile and clinical activity in trials of SCC of the
head and neck and lung, we seek to determine if the irreversible inhibition of the
ErbB family translates into clinical benefit for patients with SCC of the lung.
Methods: This trial will compare the efficacy of afatinib versus erlotinib as
second-line treatment for patients with SCC of the lung, as measured by
progression-free survival. Key patient eligibility criteria include: advanced NSCLC
squamous or mixed histology, completion of at least 4 cycles of platinum-based
doublet chemotherapy, eligible to receive EGFR-directed therapy as second-line
therapy, ECOG PS 0–1, adequate organ function, availability of archived tumour
tissue for correlative studies and no prior EGFR-directed therapy. Secondary
endpoints are comparison of overall survival, objective response rate, disease control
rate, tumour shrinkage, assessment of health-related quality of life and safety in both
treatment groups. Eligible patients will be randomized (1:1) to receive either afatinib
or erlotinib and stratified based on race (East Asian vs. other). Eight hundred
patients are planned to be enrolled globally. Independent radiological assessment of
the primary endpoint will be completed in a treatment-blinded manner. An
independent data monitoring committee will monitor safety and efficacy of the trial.
Disclosure: G. Goss: Consultant or advisory relationship to Boehringer Ingelheim,
compensated prior to conduct of the study. S. Lu: Consultant or advisory
relationship, compensated, AstraZeneca China for Iressa. A. Ardizzoni: Other
remuneration: GSK DSMC PRAME Study. V. Georgoulias: Consultant or advisory
relationship, uncompensated for GSK, Novartis, Sanofi, Janssen-Cilag, Amgen.
Honoraria and research funding from GSK, Novartis, Sanofi, Janssen-Cilag, Amgen.
S. Gadgeel: Consultant or advisory relationship for Boehringer Ingelheim. V. Chand:
Employee of Boehringer Ingelheim Pharmaceuticals, Inc. Y. Gu: Employee of
Boehringer Ingelheim Pharmaceuticals, Inc. Y.S. Olivo: Employee of Boehringer
Ingelheim Pharmaceuticals, Inc. J. Soria: Honoraria from Boehringer Ingelheim and
Roche. All other authors have declared no conflicts of interest.
510TiP DENDRITIC CELL THERAPY FOR PATIENTS WITH
REFRACTORY SOLID TUMOURS
P.P. Bapsy 1 , B. Sharan 2 , C. Kumar 2 , A. Mahmood 2 , B. Rangarajan 3 , S. Atilli 4 ,
M. Jain 5 , S. Subramanian 6 , S. Rajappa 7 , M. Srivastava 8
1 Oncology, Apollo Hospitals, Bangalore, INDIA, 2 Research and Development,
APAC Biotech Pvt. Ltd, Gurgaon, INDIA, 3 Medical Oncology, Mazumdar Shaw
Cancer Centre, Bangalore, INDIA, 4 Oncology, Bibi General Hospital, Hyderabad,
INDIA, 5 Medical Oncology, Ruby Hall Clinic, Pune, INDIA, 6 Oncology, V S
Hospital, Chennai, INDIA, 7 Medical Oncology, Basavatarakam Indo-American
Cancer Centre, Hyderabad, INDIA, 8 Clinical Research, Nextvel Consulting LLP,
Bangalore, INDIA
Background: Dendritic Cell (DC) therapy initiates immune response against tumor.
Study ongoing in 7 sites in India has objective to assess toxicity and efficacy in
refractory solid tumours.
Materials: DC therapy is prepared using Peripheral Blood Mononuclear Cells
(PBMCs), cultured with cytokines (IL4 and GMCSF) and exposed to patient’s
antigen retrieved from their own tumor tissue. Mature DCs are harvested on Day 8
and checked for surface markers (CD 80 + (PE)CD 86+ (APC) and CD 83 + ( FITC)
positive) and adequate counts (>1 million DCs) per dose. Patients with recurrent
disease on symptomatic care were enrolled and 6 doses of DC were administered
over 14 week’s period. Response criteria used are RECIST-version 1.1 (Response
Evaluation Criteria for Solid Tumours) and irRC (Immune Related Response
Criteria). Per protocol, Objective Response (OR) covers Stable Disease (SD), Partial
Response (PR) and Complete Response (CR).
Results and observations: 51 patients (ovary-9, colon and rectum- 7, head & neck -6,
lung-5, Prostate- 5, sarcoma-4, breast-4, stomach-3, cervix-3, squamous cell carcinoma
of heel-1, pancreas-1, melanoma-1, renal cell-1 and Cholangiocarcinoma-1) were
enrolled and evaluated for safety. 220 infusions have been completed. All patients
tolerated therapy well except one who had single episode of rigors during one infusion.
Annals of Oncology
Other adverse events reported were due to disease progression. Response assessment
was done at Week 8 (before dose 4), Week 14 (before dose 6) and Week 26 from start
of therapy. 33 patients’ Week 8 assessment is 22/33 (67%) OR by irRC and 9/33 (27%)
by RECIST. Among OR, 1 shows PR for 2 consecutive visits. 20 patients’ Week 14
assessment is 9/20 (45%) continuing with OR by irRC and 6/20 (30%) are OR by
RECIST. Trends suggest patients with chronic disease (average period of disease of 45
months), less metastatic sites, fewer prior chemotherapy failure and cancers like ovary,
prostate and breast, have responded well. 19 patients are on trial, 6 are alive after
withdrawal and are being followed up for survival and 26 died due to disease
progression. Survival data is yet to mature.
Conclusions: DC therapy is safe and extremely well tolerated. The response data is
encouraging. More survival data is needed to conclude survival benefit.
Disclosure: P.P. Bapsy: I am medical monitor for the study (consultant), involved
with the study design, scientific inputs and safety monitoring aspects of the study. I
am being paid a monthly professional fee for this activity. B. Sharan: I work for
APAC Biotech (sponsor) as Research Director in the R & D Department and am
being paid my monthly salary. C. Kumar: I work as Asst Director R & D for the
sponsor APAC Biotech Pvt. Ltd. I get mothly salary for my job. A. Mahmood: I
work as Senior Research Scientist in the R&D Department of APAC Biotech Pvt. Ltd
and get my monthly salary. B. Rangarajan: I am Investigator for the trial and being
compensated for my role as Clinical Research Investigator. S. Atilli: I am Investigator
for the trial and being compensated for my role as Clinical Research Investigator.
M. Jain: I am Investigator for the trial and being compensated for my role as Clinical
Research Investigator. S. Subramanian: I am Investigator for the trial and being
compensated for my role as Clinical Research Investigator. S. Rajappa: I am
Investigator for the trial and being compensated for my role as Clinical Research
Investigator. M. Srivastava: I am providing advisory consultancy to APAC Biotech
Pvt. Ltd for study operations and being paid professional fees.
1708PD MOLECULAR PROFILE AND ANTI-TUMOR ACTIVITY IN
NON-SMALL CELL LUNG CANCER (NSCLC) PATIENTS (PTS)
IN A PHASE 1 STUDY OF CABOZANTINIB (XL184) IN JAPAN
H. Nokihara 1 , N. Yamamoto 1 , S. Nakamichi 1 , H. Wakui 1 , Y. Yamada 2 , J. Frye 3 ,
A. Decillis 4 , T. Tamura 5
1 Division of Thoracic Oncology, National Cancer Center Hospital, Tokyo, JAPAN,
2 Medical Oncology, National Cancer Center Hospital, Tokyo, JAPAN, 3 Medical
Affairs, Exelixis, Inc., South San Francisco, CA, UNITED STATES OF AMERICA,
4 Clinical Development And Medical Affairs, Exelixis, Inc., South San Francisco,
CA, UNITED STATES OF AMERICA, 5 Division of Internal Medicine and Thoracic
Oncology, National Cancer Center Hospital, Tokyo, JAPAN
Background: Cabozantinib is a potent targeted therapy that inhibits MET, VEGFR2,
and RET. Anti-tumor activity in patients (pts) has been observed in a broad range of
tumors including NSCLC. The primary objective of this phase 1 study is to determine
the maximum tolerated dose (MTD) / recommended phase 2 dose in Japanese pts.
Methods: Pts with advanced solid malignancies are enrolled in successive cohorts to
receive escalating doses of cabozantinib orally once daily in a 3 + 3 trial design. Dose
limiting toxicities (DLTs) are determined using Cycle 1 data. Response is assessed
using modified RECIST v1.0. Results: As of 1 June 2012, 14 pts were enrolled
including 5 pts with non-small cell lung adenocarcinoma. Pts have been treated at 3
dose levels: 40, 60 and 80 mg. The NSCLC pts had a median of 4 prior regimens
(range, 2 – 6). Four of the 5 NSCLC pts had a confirmed partial response (cPR)
including a 51 yo female whose pre-treatment tumor sample lacked an EGFR
activating mutation Analysis of tumor obtained pre-treatment and at progression
demonstrated a KIF5B-RET fusion.
Smoking Molecular
Treatment Best
Age Gender History Profile
Duration (mos) Response
64 Female Never EGFR mutation 15+ cPR
51 Female Former EGFR wt, RET
fusion positive
9 cPR
58 Female Never EGFR wt 10 cPR
43 Male Former ALK fusion positive 4 cPR
64 Female Never EGFR wt, ALK
fusion negative
6.5 SD
DLT of Grade 3 hypertension was reported in 2 pts. The MTD using a capsule
formulation is 60 mg. Adverse events were generally mild to moderate and include
hypertension, palmar-plantar erythrodysesthesia, diarrhea, mucositis, rash, edema
and headache. Laboratory abnormalities include elevated AST/ALT, lipase and TSH;
and neutropenia and thrombocytopenia. Preliminary PK analysis showed that dosenormalized
exposure in Japanese pts is approximately 2-fold higher than in non-
Japanese pts. Despite relatively higher exposures, cabozantinib 60 mg daily appears to
be a well tolerated dose. Conclusions: Cabozantinib appears well tolerated. Signs of
antitumor activity include response and prolonged stable disease in NSCLC pts.
Accrual and additional molecular characterization is ongoing.
Disclosure: H. Nokihara: Taiho Pharmaceutical Co., Ltd, Merck Serono, Pfizer. N.
Yamamoto: Chugai pharmaceutical co., ltd., Pfizer, Kyowa-Hakko Kirin co., ltd. Y.
Yamada: Bayer, Yakult, AstraZeneca. J. Frye: Paid employee of Exelixis Exelixis stock
ownership. A. Decillis: Paid Employee of Exelixis Exelixis Stock Ownership. T.
Tamura: Chugai Pharmaceutical co., ltd., Daichi-Sankyo co., ltd., Boehringer
Ingelheim, Abbott Japan Co., Ltd, Eisai co., ltd., Bristol-Myers Squibb, Kyowa-Hakko
Kirin co., ltd. All other authors have declared no conflicts of interest.
ix174 | Abstracts Volume 23 | Supplement 9 | September 2012