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Case Study

QSP Modeling Optimizes FIH Dose Selection for Multiple Myeloma Therapy

Multiple myeloma, the second most common blood cancer, affects an estimated 160,000 individuals annually worldwide (Ludwig et al. 2020). Despite advancements in therapies like monoclonal antibodies and T-cell engages (TCEs), patients with relapsed or refractory multiple myeloma frequently face disease progression.

Ichnos Glenmark Innovation (IGI), a clinical-stage biotechnology company based in New York, is at the forefront of innovation in oncology. IGI focuses on developing cutting-edge biologics, powered by its proprietary BEAT® technology, to treat complex diseases holistically. A notable development in their pipeline is ISB 2001, a tri-specific antibody targeting BCMA and CD38, with the ability to redirect CD3+ T lymphocytes to attack tumor cells. This approach promises to overcome drug resistance commonly observed in multiple myeloma patients.

Solutions

Late Clinical

The challenge

When preparing for first-in-human (FIH) clinical trials of ISB 2001 (NCT05862012), IGI faced a significant challenge. Translating preclinical data from animals to humans often leads to an overly conservative Minimum Anticipated Biological Effect Level (MABEL) approach for dose selection. While safe, this can result in suboptimal dosing in the trial’s initial phases, unnecessarily prolonging the timeline and escalating costs. IGI needed a proven framework to determine the most appropriate therapeutic dose for their tri-specific T-cell engager.

Figure 1. Trispecific antibodies bind and bring cancer and T-cells into proximity for immune-mediated cytotoxicity. Source: https://iginnovate.com/

The solution

Certara’s Quantitative Systems Pharmacology (QSP) Center of Excellence collaborated with IGI to address the challenge. The team built a specialized QSP model for ISB 2001, leveraging their extensive biosimulation and oncology dose optimization expertise.

Key highlights of their solution include:

Developing Precision Models: Certara’s model used a Minimal Pharmacologically Active Dose (MPAD) approach. Compared to the traditional MABEL approach, this model allowed for a 50-100 times higher dose.

Regulatory Acceptance: This new approach received approvals from regulatory bodies, such as the US FDA and Australia’s HREC, supporting FIH dose determination for other TCEs as well.

The impact

The implementation of this QSP model ensured the following benefits for IGI’s clinical trial process:

Optimized Dose Selection: A higher starting dose reduced the number of patients exposed to subtherapeutic levels, enhancing efficacy evaluation in early trial phases.

Streamlined Timelines: By accelerating dose optimization, IGI minimized the overall duration and cost of the trial.

These advancements solidified IGI’s position as a trailblazer in tri-specific TCE therapy, getting life-saving treatments to patients faster.

“We were honored to work with IGI to develop a comprehensive biosimulation approach that allowed the team to successfully test ISB 2001 in virtual trials. Our unique expertise and experience using virtual patients plus mechanistic modeling solutions allowed us to accelerate the speed at which ISB 2001 gets to patients. Virtual patient technology is the future of optimizing dosing for human patients.”

Piet van der Graaf, PharmD, Ph.D.Senior Vice President and Head of QSP, Certara

“The collaboration with Certara was important for the success of ISB 2001. With the innovative QSP model adapted for our tri-specific T cell engager, we could predict a first-in-human dose with an acceptable safety margin that will expose fewer patients to sub-therapeutic dosing.”

Mario Perro, Ph.D.Head of Biologics Research, IGI

About Certara's QSP Center of Excellence

With 600+ combined years of QSP experience, 300+ completed QSP projects, and a team of 65+ expert scientists serving over 250 clients worldwide, our expertise is unparalleled. Whether you’re determining safe dosing, assessing efficacy, addressing toxicity concerns, or evaluating competitive benchmarks, our team is here to help you make informed, data-driven decisions.

Leverage the world’s largest QSP team to tackle your most challenging questions and accelerate your drug development with confidence. At Certara, we’re bridging the gap between promising therapeutic innovations and meaningful patient outcomes. Partner with our QSP Center of Excellence to advance your drug development program confidently.

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Press Release

Certara & Ichnos Glenmark Innovation Collaboration Optimizes Dosing Strategy for Potential First-In-Class Cancer Drug

Publication

ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells