A Phase I, Multicenter, Open-Label, Dose-Escalation, Multidose Study of MDX-1203 in Subjects With Advanced/Recurrent Clear Cell Renal Cell Carcinoma or Relapsed/Refractory B-Cell Non Hodgkin's Lymphoma

The purpose of this study is to determine if MDX-1203 is safe for the treatment of renal cell carcinoma or non-hodgkin's lymphoma.

Start Date01 Jul 2009

Sponsor / Collaborator

Bristol Myers Squibb Co.

100 Clinical Results associated with MDX-1203

100 Translational Medicine associated with MDX-1203

100 Patents (Medical) associated with MDX-1203

Literatures (Medical) associated with MDX-1203

01 Aug 2021·Drug Discovery TodayQ2 · MEDICINE

Duocarmycin-based antibody–drug conjugates as an emerging biotherapeutic entity for targeted cancer therapy: Pharmaceutical strategy and clinical progress

Q2 · MEDICINE

Review

Author: Zhao, Hui ; Wang, Ming-Hai ; Yao, Hang-Ping ; Tong, Xiang-Min ; Hudson, Rachel

Duocarmycins are a class of DNA minor-groove-binding alkylating molecules. For the past decade, various duocarmycin analogues have been used as payloads in the development of antibody-drug conjugates (ADCs). Currently, more than 15 duocarmycin-based ADCs have been studied preclinically, and some of them such as SYD985 have been granted Fast-Track Designation status. Nevertheless, progress in duocarmycin-based ADCs also faces challenges, with setbacks including the termination of BMS-936561/MDX-1203. In this review, we discuss issues associated with the efficacy, pharmacokinetic profile, and toxicological activity of these biotherapeutics. Furthermore, we summarize the latest advances in duocarmycin-based ADCs that have different target specificities and linker chemistries. Evidence from preclinical and clinical studies has indicated that duocarmycin-based ADCs are promising biotherapeutics for oncological application in the future.

01 Jan 2016·Cancer Chemotherapy and PharmacologyQ4 · MEDICINE

First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70

Q4 · MEDICINE

Article

Author: Owonikoko, Taofeek Kunle ; Stadler, Walter Michael ; Ahlers, Christoph Matthias ; Gulati, Parul ; Cardarelli, Pina M ; Smith, David C ; Cohen, Lewis J ; Kluger, Harriet ; Hussain, Arif ; Molina, Ana M ; Shah, Aadhar

PURPOSEThe study evaluated the safety, tolerability, and pharmacokinetics of BMS-936561, a fully human monoclonal antibody-drug conjugate targeting CD70 cell-surface protein.METHODSEligible patients had ECOG performance status 0-2 and received ≤3 prior chemotherapy regimens. An initial accelerated titration design enrolling one patient per dose level was followed by 3 + 3 dose escalation with the first observation of a grade ≥2 adverse event (AE). We tested escalating doses of BMS-936561 (0.5, 1, 2, 4, 8, 15 mg/kg) administered every 21 days in a 42 day cycle for a maximum of 17 cycles. Pharmacokinetic samples were collected in cycle 1.RESULTSA total of 26 patients enrolled; 16 and 10 for the escalation and expansion cohorts, respectively. Median age was 63 years (48-74); 18 males and 25 Caucasians. There was no defined MTD per protocol, but a DLT of grade 3 hypersensitivity was recorded in 2 of 16 (13%) subjects at the highest dose of 15 mg/kg. The most frequent AEs were: fatigue (85%), nausea (54%), and decreased appetite (39%). Delayed toxicities (facial edema and pleural/pericardial effusions) occurred in 6 of 16 (38%) subjects at the 15 mg/kg dose. PK analysis showed a dose-proportional increase in active drug levels with increasing doses. There was disease stabilization in 18 of 26 patients (69%) without correlation with received dose.CONCLUSIONSBMS-936561 is well tolerated over a wide range of doses in patients with advanced ccRCC and B-NHL. The 8 mg/kg dose was the highest best tolerated dose and the recommended dose for future studies.

01 May 2013·BioanalysisQ4 · MEDICINE

Novel Detection of DNA-Alkylated Adducts of Antibody–Drug Conjugates with Potentially Unique Preclinical and Biomarker Applications

Q4 · MEDICINE

Article

Author: Deshpande, Shrikant ; Chong, Coling ; Rangan, Vangipuram ; Wang, Zemin ; Cardarelli, Pina ; Thevanayagam, Lourdes ; Srinivasan, Mohan ; Pan, Chin ; Rao, Chetana ; Bell, Alasdair ; Gangwar, Sanjeev ; Zang, Allen ; Chakraborty, Indrani ; Sufi, Bilal

Background: MDX-1203 is an antibody–drug conjugate (ADC) currently in clinical trials for the treatment of renal carcinoma. The active ingredient of MDX-1203 is a DNA minor groove-binding cytotoxic drug that forms a covalently linked adduct with an adenine base. Formation of this adenine adduct prevents DNA replication, thus triggering cell death. Results: A method has been developed to successfully isolate, identify and quantitate the adenine adduct using LC–MS/MS. The method is highly useful to validate the mode of action of this class of ADCs. Additionally, we have demonstrated that this method could potentially be utilized to assess the efficacy of the ADC in in vitro studies by measuring the amount of adenine adduct in various cells expressing the antigen. Conclusion: Upon validation, this method could serve as an invaluable tool to evaluate compounds in preclinical in vivo models and in utilizing the DNA adduct as a potential biomarker.

100 Deals associated with MDX-1203

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Renal Cell Carcinoma	Phase 2	US	Bristol Myers Squibb Co.	01 Jul 2009
B-cell lymphoma recurrent	Phase 1	US	Bristol Myers Squibb Co.	01 Jul 2009
B-cell lymphoma refractory	Preclinical	US	Bristol Myers Squibb Co.	01 Jul 2009

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00944905 (CA211-001, ASCO2014) Manual	Phase 1	B-Cell Lymphoma \| Renal Cell Carcinoma	26	BMS-936561	(jjtgqmtvzt) = fzulaaexbu attoecwsmj (hpbklsmiti ) View more	Positive	20 May 2014

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