ADC Therapeutics ADCT shares plunged 53.4% in after-hours trading on Wednesday despite the company reporting positive top-line results from a late-stage confirmatory study of Zynlonta in combination with Roche’s RHHBY Rituxan (rituximab) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). While the study achieved its primary efficacy endpoint and showed improvements across several key measures, investors appeared focused on safety findings indicating higher rates of serious adverse events, treatment discontinuations and fatal adverse events in the experimental arm.
Zynlonta, ADC Therapeutics' CD19-targeted ADC, is already approved in the United States under the FDA's accelerated approval pathway and has received conditional approval in Europe for adult patients with relapsed or refractory DLBCL after two or more lines of systemic therapy. The drug is also being evaluated in combination regimens and in earlier treatment settings as ADCT seeks to expand its clinical and commercial reach.
The phase III LOTIS-5 confirmatory study compared Zynlonta plus Roche’s Rituxan against the standard immunochemotherapy regimen, Rituxan, gemcitabine and oxaliplatin (R-GemOx), in patients whose disease had relapsed or become refractory after at least one prior line of systemic treatment. The study met its primary endpoint of progression-free survival (PFS), with a median PFS of 6.1 months for the Zynlonta-based regimen compared to 4.7 months for R-GemOx.
Secondary efficacy measures also favored the experimental therapy. Overall response rate reached 58.1% compared with 45.2% for the control regimen, while complete response rates were 39.5% and 26.7%, respectively. Median duration of response improved to 9.2 months from 7.7 months, and median duration of complete response extended to 16.8 months versus 12.3 months. Notably, nearly half of patients achieving complete remission with the Zynlonta combination remained in remission at 24 months compared with 16.7% in the control group. Overall survival showed no detrimental effect relative to R-GemOx.
Year to date, ADC Therapeutics shares have lost 12.7% compared with the industry’s 4.7% decline.
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ADCT’s Safety Findings Overshadow Positive Efficacy Results
Despite the favorable efficacy profile, investors appeared concerned by the safety data disclosed by ADC Therapeutics alongside the top-line results. Although overall treatment-emergent adverse event rates were broadly similar between the two treatment arms, several important safety measures were notably worse in patients receiving Zynlonta plus Roche’s Rituxan.
The incidence of serious adverse events was substantially higher in the experimental arm, affecting 49% of patients compared with 34.5% in the control group. Treatment-emergent adverse events leading to withdrawal of study medication were also significantly more frequent, occurring in 25.5% of patients receiving the Zynlonta combination as compared to only 9.1% among those treated with R-GemOx.
Particular attention was drawn to the higher rate of Grade 5 treatment-emergent adverse events, which generally represent fatal events. ADC Therapeutics reported 27 such cases, or 13.2% of patients, in the Zynlonta arm compared with nine cases, or 4.6%, in the control group. The company noted that most Grade 5 events in the experimental arm occurred in patients aged 75 years or older, but the imbalance nevertheless raised concerns among investors.
While hematologic toxicities were more common in the control arm, the Zynlonta regimen was associated with higher rates of infection/infestations, hepatotoxicity and edema/effusion. These findings, combined with elevated rates of serious and fatal adverse events, likely fueled concerns regarding the overall benefit-risk profile that regulators may ultimately consider during the review process.
ADCT Prepares Regulatory Filing and Strategic Review
Following the positive efficacy outcome, ADC Therapeutics plans to engage with the FDA regarding the overall benefit-risk assessment of Zynlonta plus Roche’s Rituxan. The company intends to hold a pre-supplemental biologics license application (sBLA) meeting with the agency in August as it prepares for a regulatory submission.
ADC Therapeutics is targeting an sBLA filing in the fourth quarter of 2026 to support broader use of the regimen in relapsed or refractory DLBCL. At the same time, ADCT said it will continue evaluating a range of value-maximizing initiatives, including potential near-term cost-reduction measures, as it navigates the next stage of development and regulatory review for the therapy.
ADC Therapeutics SA Price and Consensus
ADC Therapeutics SA price-consensus-chart | ADC Therapeutics SA Quote
ADCT’s Zacks Rank & Stocks to Consider
ADC Therapeutics currently carries a Zacks Rank #4 (Sell).
Some better-ranked stocks in the biotech sector are Liquidia Corporation LQDA and Immunocore IMCR, each sporting a Zacks Rank #1 (Strong Buy) at present. You can see the complete list of today’s Zacks #1 Rank stocks here.
Over the past 60 days, estimates for Liquidia Corporation’s 2026 EPS have increased from $1.50 to $2.97. Over the same period, EPS estimates for 2027 have also increased from $2.91 to $4.81. LQDA shares have rallied 61.5% year to date.
Liquidia Corporation’searnings beat estimates in three of the trailing four quarters and missed in the remaining one, with the average surprise being 54.40%.
The estimate for Immunocore’s 2026 EPS is currently pegged at 6 cents. In the past 60 days, the estimates for its 2027 EPS have increased from 24 cents to 87 cents. IMCR shares have lost 4.7% year to date.
Immunocore’s earnings beat estimates in three of the trailing four quarters, while missing the same on the remaining occasion, with the average surprise being 46.66%.
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