ADC Therapeutics Reports 89.8% Response Rate for ZYNLONTA Combo in DLBCL—Will This Change Treatment Expectations?
Combination Therapy Delivers Nearly 90% Response Rate in Challenging Patient Population
ADC Therapeutics (NYSE: ADCT) unveiled new data from its LOTIS-7 Phase 1b trial showing that ZYNLONTA® (loncastuximab tesirine-lpyl), when combined with the bispecific antibody glofitamab (COLUMVI®), produced an overall response rate (ORR) of 89.8% among 49 evaluable patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The results, based on at least six months of follow-up, also included a striking 77.6% complete response (CR) rate. In the world of blood cancers where second-line therapies often face resistance, such results stand out and could alter treatment strategies in the near future.
Strong Responses Observed in Both Relapsed and Refractory Cases
What sets these findings apart is the regimen’s performance in distinct subgroups. For relapsed patients, the ORR was a perfect 100%, and the CR rate hit 91.7%. In the primary refractory group—historically more challenging to treat—ORR was 80% with a 64% CR rate. Furthermore, six out of eight patients who previously failed CAR-T cell therapy achieved a complete response.
| Patient Subgroup | ORR (%) | CR Rate (%) |
|---|---|---|
| Overall (n=49) | 89.8 | 77.6 |
| Relapsed (n=24) | 100.0 | 91.7 |
| Primary Refractory (n=25) | 80.0 | 64.0 |
| Post-CAR-T (n=8) | 75.0 | 75.0 |
Durability and Safety Profile Add Weight to the Data
Of the 38 patients achieving a complete response, 33 remained in CR at the time of data cutoff—suggesting durability of remission. Fourteen patients converted from stable or partial response to CR over time. In addition, the combination showed a manageable safety profile. The most common severe (grade 3 or higher) side effects were neutropenia (32.7%), increased GGT (16.3%), anemia (10.2%), decreased white blood cell count (8.2%), generalized edema (8.2%), and elevated liver enzymes. Grade 5 adverse events (AEs) occurred in two patients (4.1%). Cytokine release syndrome (CRS), a known risk in this class, was observed in 36.7% of patients, predominantly low grade at the chosen dose.
| Adverse Event | Incidence (%) |
|---|---|
| Neutropenia (Grade 3+) | 32.7 |
| Increased GGT | 16.3 |
| Anemia | 10.2 |
| CRS (any grade) | 36.7 |
| ICANS (Grade 1/2) | 4.1 |
| Grade 5 AE (Any cause) | 4.1 |
Enrollment to Complete in 1H 2026—What’s Next for ADCT?
The company is targeting full enrollment of approximately 100 patients at the selected 150 µg/kg dose by mid-2026, with plans to present comprehensive data and seek publication by year’s end. Alongside results from the ongoing LOTIS-5 trial expected in the first half of 2026, ADC Therapeutics is positioning ZYNLONTA-based regimens as complementary solutions to improve outcomes for 2L+ DLBCL patients. These robust early-phase results could inform regulatory strategy and broader market adoption if durability and safety hold up in larger cohorts.
Key Takeaway: Results Reinforce Potential for ZYNLONTA Combinations in Difficult-to-Treat Lymphoma
While it’s still early and confirmatory data from larger trials will be essential, the nearly 90% ORR—paired with high CR rates, manageable toxicity, and notable efficacy even after CAR-T failure—marks the ZYNLONTA and glofitamab combination as one of the more compelling emerging therapies in the DLBCL space. Investors and clinicians will want to watch closely for full LOTIS-7 data and the forthcoming results from LOTIS-5, as these may set new standards for second-line lymphoma care. For now, these interim results keep expectations high for ADC Therapeutics and the patients waiting for better treatment options.
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