CALL FOR PARTNERSHIP MULTIPLI PROGRAM

Transcription

1 CALL FOR PARTNERSHIP MULTIPLI PROGRAM

2 I. Introduction The MULTIPLI program, coordinated by Inserm (the French National Institute of Health and Medical Research) and the Cancer Institute of the French National Alliance for Life Sciences and Health (Aviesan Cancer Institute), is the first French personalized medicine trial implementing full exomeand RNA-sequencing for clinical decision making in the field of Cancer. MULTIPLI takes place within the framework of the French Genomic Medicine 2025 plan. This ambitious plan, coordinated and supported by the French Government, aims at positioning France in the first major countries committed in the genomic medicine. In addition, to respond to public health challenges in terms of diagnosis, prognosis and therapeutics, this plan also foresees the emergence of a national medical and industrial branch in genomic medicine of which the know-how might be exported. The main objective of MULTIPLI is to assess the benefit of genomic-guided therapies versus conventional therapy in two cancers (sarcomas and colon cancers). MULTIPLI encompasses 2 innovative personalized medicine clinical trials in metastatic of soft tissues sarcoma (MULTISARC) and colorectal carcinoma (ACOMPLI) involving targeted molecules according to the tumor profile of each patient. Following the publication of the French Genomic Medicine 2025 plan, some pharmaceutical companies have contacted the MULTIPLI team to demonstrate their interest to participate in this program and with some of them, preliminary discussions are ongoing. Beyond the drugs developed by these companies, Inserm, as sponsor of the MULTIPLI clinical trials, wants to offer to patients an access to an even larger panel of innovative drugs. For this purpose, Inserm has decided to propose to all the scientific industrial community, French and international companies involved in oncology, the opportunity to participate to the MULTIPLI program. To ensure transparency and equal treatment between the industrial actors who might be interested in participating in MULTIPLI program, Inserm launches a call for partnership. This call aims to bring together academic and industrial actors as partners of the cancer genomic medicine program, a strategic and high-priority effort in France. Sharing this common objective, we invite each pharmaceutical company, regardless their size, to join the MULTIPLI Program by applying to this call. By combining the scientific strengths of academic research teams involved in the MULTIPLI program with the innovative drugs developed by pharmaceutical companies, we have the ambition to provide the best up to date management for cancer patients. Yves Levy Chairman and CEO of Inserm 1

3 II. Presentation of the MULTIPLI (MULTIsarc and AcomPLI) clinical trials and partnership proposal A. Rational of the MULTIPLI trials Personalized cancer therapy has been recognized to require two critical steps: first, a comprehensive assessment of the biological characteristics of tumors from each individual, and second, validated biomarkers that identify subgroups of patients most likely to benefit from a given therapy. Fine tuning of the biological characteristics of tumors is now accessible as the price of whole genome sequencing falls to reach less than 1,000 Euros per genome' mark. This technology is now proven effective to be analyzed small clinical tumor tissue specimens. Genome sequencing to determine specific information of interest for all cancer patients will be a precious tool in the development of personalized therapies. To face these challenges, the French government announced that it plans to invest 670 million in a genomics and personalized medicine program meant to improve health outcomes in the country. This plan is named France Genomic Medicine The effort aims to establish 12 sequencing platforms throughout the country, and two national centers for genomic expertise and data analysis that will ensure that the platforms are consistent and regularly updated. This program is disease focused as it plans to begin with rare diseases, cancers, and specific forms of diabetes. In this context, Inserm (the French National Institute of Health and Medical Research) and the Cancer Institute of the French National Alliance for Life Sciences and Health (Aviesan Cancer Institute) have been given a mandate to pilot the first French disease genomic medicine program in the field of Cancer, the MULTIPLI trial. MULTIPLI is also within the objectives of the 3rd French Cancer Plan ( ). Thus, the MULTIPLI trial has as main objective to assess the benefit of genomic-guided therapies versus conventional therapy. The MULTIPLI trial encompasses 2 innovative personalized medicine clinical trials in metastatic of soft tissues sarcoma (MULTISARC) and colorectal carcinoma (ACOMPLI) involving targeted molecules according to the tumor profile of each patient. MULTIPLI represents the first clinical study implementing exome sequencing and RNA sequencing for clinical decision making. MULTIPLI s primary purpose is to demonstrate that implementation of next-generation sequencing improves survival of patients with advanced disease. The secondary aim consists to use the data obtained from high throughput sequencing to analyze the genetic networks involved in sensitivity and resistance to anti-cancer therapies. The purpose of the MULTIPLI trials is to evaluate the benefit of this approach for the decision concerning the treatment. Each clinical trial is thus divided into two steps: the first step called, 0 (MULTISARC-0 and ACOMPLI-0), is designed to identify actionable molecular alterations in Soft Tissues Sarcoma (STS) or metastatic ColoRectal Carcinoma (mcrc) patients with advanced disease through the use of exome sequencing and RNA sequencing for all registered patients. In a second step, patients will be enrolled in one of the clinical trials called MULTISARC-1, 2, 3,, N and ACOMPLI-1, 2, 3,, N according to the sequencing data identifying an actionable genetic alteration. In each clinical trial, patients will be randomized in two groups: one group treated with a MULTIPLI drug and one group treated according to current standard approaches. Patients in the group treated with a MULTIPLI drug will be given a targeted drug supplied by an industrial company partner of this call. 2

4 The MULTIPLI (MULTISARC and ACOMPLI) trials are sponsored by Inserm. Queries related to the design of MULTISARC and/or ACOMPLI clinical trials can be sent to: These targeted-based clinical trials constitute a major step to demonstrate the interest and the feasibility of a national implementation of the tumor exome and transcriptome sequencing and the deployment of diagnostic high-throughput technologies in clinical practice and to face the challenge of personalized genomic medicine. The preliminary MULTIPLI trials timetable is detailed below: - Enrollment start : April Enrollment duration : 36 months - Trial duration : 5 years B. The MULTIPLI industrial partnership Cancer Research has become a strategic and high-priority effort in France to improve prevention, diagnosis and treatment of patients with cancer. For years, academic and industrial scientific communities have shared common objectives and worked together for both improving the quality of life of patients with cancer and their survival. The purpose of this call aims to bring together the academic and industrial actors around the cancer genomic medicine which would allow patients with metastatic soft-tissue sarcoma and colorectal cancer to benefit from personalized diagnostic and therapeutic care by sequencing their genome (whole exome and transcriptome). This call is addressed to pharmaceutical companies with a strong involvement in personalized medicine in the field of oncology willing to be part of the ambitious initiative of the French Government and ready to initiate a novel partnership on the basis of the scientific excellence of the academic teams at the origin of the MULTIPLI program. Industrial scientists are invited to submit proposals of their commitment to supply one or more drugs suitable for the MULTISARC and/or ACOMPLI clinical trials. The partnership principle is based on the supply of the drug by the pharmaceutical company, while all over costs related to the randomized MULTIPLI clinical trials will be funded by Inserm and its academic partners. Being partner to the MULTIPLI program means: - To be involved in the first oncology genomic medicine trials implementing exome sequencing and RNA sequencing in the clinical decision making - To be an important partner of the French Government by participating to the French Genomic Medicine Program from which results could imply changes in the future healthcare circuit of patients suffering from cancer - To be part of an innovative public/private partnership based on oncology personalized medicine - To be involved in the 3 rd French Cancer Plan III. Requirements of the call A. Objectives of the call The call focuses on industrial partners (French or international companies) who can supply drugs with an established recommended phase 2 dose, regardless of the medical indication, that can be matched with one or more genetic alterations in patients with advanced solid tumors. 3

5 B. Who can apply? Pharmaceutical companies, whatever their size, which develop targeted therapies matching with one or more genetic alterations occurring in advanced solid tumors, may apply to this call. C. How do apply? The applicant should fill the application form as proposed in annex and send it to More than one drug can be proposed per application. Only complete application forms along with all required documents will be considered. D. Eligibility criteria Each drug provided by the applicant should: - Present an established recommended phase 2 dose (regardless of the medical indication) as a single agent or in combination if applicable - Inhibit, at least, the activity of one of the following proteins: ALK, AKT, ATM, ATR, BRAF, CDK4/6, CSF1R, EGFR, EZH2, FGFR1,2,3, HER2, HER3, KIT, MDM2, MEK1, MET, mtorc1, mtorc2, NOTCH1,2,3,4, NTRK1/2/3, PARP1, PDGFRA, PI3KCA, RET, ROS1, SMO, VEGFR2, WEE1. Drugs that inhibit other proteins involved in similar pathways will also be considered. - Be supplied for the expected duration of the clinical trial (1st patient accrual: Q2 2017, inclusion period: 36 months). The application form should be addressed before the 31 th of January, 2017 at 6 pm (CET). IV. Selection criteria A. Assessment procedure A notification will be sent by to the applicant to confirm the receipt of its proposal. The proposal will be checked and considered as eligible if all required information and/or documents have been provided. If the application does not contain all required documents, the proposal will be returned to the applicant with a request for adjustments or additional information. In case, these information or documents would not be transmitted within 10 working days following the request, the submitted application will be rejected and not considered. B. Assessment process The evaluation of all applications received during the call will be overseen by the MULTIPLI Executive Committee. MULTIPLI Executive Committee will propose a final selection of drugs in respect to the purpose of MULTIPLI and eligibility criteria. The Executive s Committee selection will be reviewed and validated by the MULTIPLI Scientific Advisory Board (SAB). The SAB includes international independent experts (2 mcrc experts, 2 STS experts, 1 methodology and biostatistics expert, 1 NGS expert) and representative(s) of the MULTIPLI. The selection of drugs will be based on a careful and independent review. Drug(s) will be favored on the basis of the following criteria: - The drug (s) with the most complete and advance information regarding its development, its benefits (anti-tumor activity) and its potential risks (safety profile as occurrence of grade III SAE or toxicity activity) - The drug (s) which has been used to treat the highest number of patients - Drug(s) with a marketing authorization from FDA or EMA 4

6 The Scientific Advisory Board members and independent experts will be submitted to the confidentiality of all information transmitted by the applicant in the application form. Submission of similar proposals In case of submissions proposing identical or very similar drugs, the application that fulfills the most relevant criteria including a higher number of drugs will be favored. Application date may also be take into account. IV. Timeframe A. Deadline for the submission of tenders Application form should be submitted electronically at multipli.isp@inserm.fr. The deadline for submission is the 31 th of January 2017 at 6 pm (CET). 24 hours following the submission, the applicant will receive a receipt by . B. Timeline Call publication: the 22 th of November, 2016 Deadline for submission: the 31th of January, 2017 at 6 pm (CET) Assessment by MULTIPLI Executive Committee: Early February 2017 Assessment by MULTIPLI Scientific Advisory Board: Mid-February 2017 Final decision given by the MULTIPLI SAB: the 28 th of February, 2017 Notification to applicant: Early March

7 V. Process Application proposal Proposal should contain: Detailed information about applicants Drug description (according to the application form available in appendix) Submission proposal The 31th of January 2017, 6 pm One application form submitted per company Template and guideline should be respected Application language is english Proposal submission via multipli.isp@inserm.fr Evaluation proposal MULTIPLI board will consider eligible proposal based on: The most complete and advance information on drug(s) regarding its benefits (antitumor activity) and its potential risks (safety profile as occurrence of grade III SAE or toxicity activity) The highest number of patients who have been already treated by provided drug(s) Drug(s) with a marketing authorization from FDA or EMA A grant award letter will be sent to selected applicants Final decision VI. After award The applicant will receive an award letter. Afterward, a partnership agreement will be signed with the applicant to set out the legal conditions of drug supply. Except all legal terms concerning the drug(s) and the associated safety conditions, all other legal terms of this agreement including both Intellectual property and publication conditions will be shared by all selected industrial applicants. V. Contact information For any further information on the call, the applicant can send an to multipli.isp@inserm.fr 6

8 VI. Annex: Application form 1 Applicant information Name (national name and its translation in EN or FR if applicable) Business name (if different) Short name Legal form Organization type For profit Non for profit Non-Governmental Organization Registration number (registration number in the national register of companies) VAT number Postcode City 1

9 Region (if applicable) Country 2 Legal representative information The Applicant shall identify the legal representative authorized to sign the Partnership Agreement who represents the applicant. Surname First name Position/Function Title Mailing address Phone Mobile Fax address 3 Contact person responsible for the proposal Surname First name Position/Function Title Mailing address 2

10 Phone Mobile Fax address 4 Drug(s) provided by applicant Regimen description Drug Dose Route Schedule of drug administration Duplicate line if necessary Duration MULTIPLI clinical trial For approved drugs, indication(s) covered by the marketing authorization MULTISARC ACOMPLI MULTISARC ACOMPLI MULTISARC ACOMPLI MULTISARC ACOMPLI Available in Q Yes No Yes No Yes No Yes No 3

11 Target Protein activity inhibitor Drug ALK AKT ATM ATR BRAF CDK4/6 CSF1R EGFR EZH2 FGFR1,2,3 HER2 HER3 KIT MDM2 MEK1 MET mtorc1 mtorc2 NOTCH1,2,3,4 NTRK1/2/3 PARP1 PDGFRA PI3KCA RET ROS1 SMO VEGFR2 WEE1 5 References Please provide available scientific data regarding each drug (for example, Summary of Product Characteristics, clinical study reports, clinical trials publications, ) All available publications which demonstrate the scientific benefit (anti-tumor activity) and the safety of each proposed drug can be add in below or specify in an annexed document. 4