As Dr. Yael Cohen presented her team's clinical trial results at ASCO 2023, the hope in the air was palpable. Veteran myeloma specialists hosting the session listened with wide eyes and enormous smiles as what would seem like a simple Phase 1 Trial resulted in ground-breaking myeloma advances. 

This was the first time two bi-specifics had been combined in treatment against a hematological malignancy. 

Interesting things to note about this specific trial: 

• Talquetamab, one of the bi-specifics used in this clinical trial, is not currently FDA-approved for use in the United States. However, the drug is before the FDA, and we hope to see its approval soon. 
• The primary objective of this trial was to evaluate the safety of the regimen, but its secondary objectives resulted in some of the most positive response rates that myeloma treatments in clinical trials have ever had. 
• This trial included a subset population of patients with extramedullary disease, which can result in plasmacytomas throughout the body and can be very difficult to treat. 

You can listen to Dr. Cohen's summary of the trial and its powerful results or read the written synopsis below: 

What question was the clinical trial trying to answer? What phase was this trial in? 

Is the combination of teclistimab and talquetamab safe for patients? 

This was a Phase I (1) clinical trial, meaning that its primary purpose was to evaluate the safety profile of the combination. However, the secondary objectives of the trial included preliminary anticancer activity of each arm of the study. 

How many people participated, and what were the qualifications? 

Ninety-three (93) patients were enrolled. 

The requirements included measurable myeloma, relapsed/refractory myeloma or intolerant to the last line of therapy, and they had to have been exposed to a proteasome inhibitor (such as bortezomib/VELCADE), immunomodulatory drug (such as lenalidomide/REVLIMID), and anti-CD38 therapy (such as daratumumab/DARZALEX).

How long did the study last, and when was it completed? 

It began on December 15, 2020, and the median (range) duration of follow-up was 14.4 months. Phase 1 should conclude on November 16, 2023. 

The study has entered phase 2, and the estimated completion date is March 24, 2024.

What are the preliminary results? 

The regimen proved to be a safe option for myeloma patients. No unexpected side effects were reported as a result of combining the new drugs. As expected, there were incidences of cytokine release syndrome consistent with other immunotherapies, but they were treatable, and all CRS events were resolved at data cutoff. 

Infections were common and mostly low grade. 

Across all dosing levels, the overall response rate (ORR) was 86.6%, but in the dosing arm of teclistimab 3.0 mg/kg + Tal 0.8 mg/kg, the overall response rate was 96.3%. 

At the data cutoff, 61% of patients remained on the treatment. 

An overall response rate (ORR) of 83% was achieved in patients with extramedullary disease (as seen below). There will be an extramedullary disease cohort opening based on these promising results, with overall safety and efficacy supportive of future explanation in larger studies. 

Why is this important to patients in today's myeloma?

Bispecific therapy creates promising opportunities for myeloma patients. But there are many of them! Combining them for a more effective purpose is a worthwhile opportunity when trying to achieve deep and lasting responses, especially in tough-to-treat myeloma, like extramedullary disease. It will be important to keep our eye on Phase II (2) and Phase III (3) of this trial moving forward. There is a lot of hope on the myeloma horizon! 

We want to thank the following researchers and specialists who made this trial possible, along with the clinical trial participants and their supportive caregivers. 

Yael C Cohen, Daniel Morillo, Moshe E Gatt, Michael Sebag, Kihyun Kim, Chang-Ki Min, Albert Oriol, Enrique M Ocio, Sung-Soo Yoon, Maria-Victoria Mateos, Michael Chu, Paula Rodríguez-Otero, Irit Avivi, Yue Guo, Maria Krevvata, Michelle R. Peterson, Melissa Jo Beelen, Jill Vanak, Arnob Banerjee, Hila Magen