510TiP - Dendritic cell therapy for patients with refractory solid tumours

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Clinical Research
Basic Scientific Principles
Presenter Poonamalle Padmanabhan Bapsy
Authors P.P. Bapsy1, B. Sharan2, C. Kumar2, A. Mahmood2, B. Rangarajan3, S. Atilli4, M. Jain5, S. Subramanian6, S. Rajappa7, M. Srivastava8
  • 1Medical Oncology, Apollo Hospitals, BANGALORE/IN
  • 2Research And Development, APAC Biotech Pvt. Ltd, Gurgaon/IN
  • 3Medical Oncology, Mazumdar Shaw Cancer Centre, Bangalore/IN
  • 4Oncology, Bibi General Hospital, Hyderabad/IN
  • 5Medical Oncology, Ruby Hall Clinic, Pune/IN
  • 6Oncology, V S Hospital, Chennai/IN
  • 7Medical Oncology, Basavatarakam Indo-American Cancer Centre, Hyderabad/IN
  • 8Clinical Research, Nextvel Consulting LLP, Bangalore/IN

Abstract

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. 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.