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Eyes On Pharma Blog 

EyesOn Oncology Clinical Data

  • Writer: Jana Chisholm
    Jana Chisholm
  • 8 hours ago
  • 3 min read


Three recent clinical updates illustrate the opportunities and challenges facing next-generation oncology therapies.

  • ADC Therapeutics reported positive efficacy data for Zynlonta in second-line diffuse large B-cell lymphoma (DLBCL), but unexpectedly high mortality rates raised concerns that overshadowed the progression-free survival benefit.

  • Innovent and Takeda strengthened their position in the rapidly expanding CLDN18.2 field with a Phase 3 success for IBI343 in gastric cancer.

  • Meanwhile, Caribou Biosciences reported encouraging long-term data for its off-the-shelf CAR-T therapy, potentially validating a new approach to cell therapy delivery.



ADC Therapeutics


Zynlonta

ADC Therapeutics entered 2026 hoping that LOTIS-5 would expand the use of Zynlonta (loncastuximab tesirine) from third-line to second-line DLBCL.


The study enrolled 440 patients with relapsed or refractory diffuse large B-cell lymphoma. Patients received:

Experimental Arm

  • Zynlonta + Rituxan

Control Arm

  • Rituxan + gemcitabine + oxaliplatin

 

Key Efficacy Results

  • Progression-free survival:

    • 6.1 months vs 4.7 months

  • Complete response rate:

    • 39.5% vs 26.7%

  • Duration of complete response:

    • 16.8 months vs 12.3 months

The Safety Concern

  • Deaths occurred in:

    • 27 patients (13.2%) in the treatment arm

    • 9 patients (4.6%) in the control arm

  • The treatment arm also experienced:

    • More serious adverse events (49% vs 34.5%)

    • More treatment discontinuations (25.5% vs 9.1%)


The company stated that infections among patients aged 75 and older accounted for many of the deaths and argued that longer follow-up may have contributed to the imbalance.


What to Watch

The August FDA meeting will be critical. The key question is whether regulators view the efficacy gains as sufficient to offset the observed safety imbalance.


For ADC Therapeutics, the stakes are substantial. Zynlonta generated only $74 million in revenue during 2025 and remains the company's sole commercial product. A successful expansion into earlier lines of therapy could materially change the company's trajectory.


Takeda / Innovent


IBI343 and the Race for CLDN18.2 Leadership


Why CLDN18.2 Matters

Claudin 18.2 (CLDN18.2) has become one of the most actively pursued targets in gastrointestinal oncology.

The protein is highly expressed in:

  • Gastric cancer

  • Gastroesophageal junction cancer

  • Certain pancreatic cancers


Astellas validated the target through FDA approval of an anti-CLDN18.2 therapy, but many companies believe there is room for improved approaches.


The broader competitive landscape includes:

  • Takeda / Innovent

  • AstraZeneca

  • Astellas

  • Moderna

  • Multiple Chinese biotechs


All pursuing CLDN18.2-based therapies through antibodies, bispecifics, and ADCs.

 

Phase 3 Success

Innovent enrolled 464 patients with:

  • Locally advanced

  • Unresectable

  • Metastatic

CLDN18.2-positive gastric or gastroesophageal junction cancers.


Patients had already received at least two prior systemic therapies.

The trial met one of its primary endpoints:

  • Statistically significant improvement in progression-free survival versus investigator-choice chemotherapy

Although full data have not yet been released, clinicians described:

  • Strong efficacy

  • Favorable tolerability

  • Low rates of gastrointestinal toxicity


Caribou Biosciences


Current CAR-T Therapy

Approved autologous [patient-derived] CAR-T therapies such as:

  • Yescarta

  • Breyanzi

have transformed lymphoma treatment.


However, they remain difficult to manufacture and deliver. Patients must:

  1. Undergo cell collection

  2. Wait for manufacturing

  3. Receive treatment weeks later


Some patients never receive therapy because disease progression occurs before manufacturing is completed.


Caribou's Off-the-Shelf CAR-T

Caribou Biosciences may have delivered one of the more interesting datasets of the year.

Vispa-cel uses donor-derived cells rather than patient-derived cells. This creates an "off-the-shelf" therapy that can be administered immediately.


Updated Clinical Results

Among 27 second-line large B-cell lymphoma patients:

  • Median progression-free survival:

    • 17.1 months

  • Comparison:

    • Yescarta: 14.9 months

    • Breyanzi: 14.8 months

  • The therapy also demonstrated:

    • No graft-versus-host disease

    • No Grade 3+ neurotoxicity

    • One Grade 3+ cytokine release syndrome event

Safety concerns remain.

  • Investigators reported:

    • One treatment-related death

    • Persistent cytopenias

    • Multiple infections

Nevertheless, the overall profile remains encouraging.


The Bigger Opportunity

Caribou's commercial thesis is not necessarily to outperform existing CAR-T products.

Instead, the company hopes to expand access. Only approximately 25% of eligible second-line lymphoma patients currently receive autologous CAR-T therapy. If an off-the-shelf product can deliver comparable outcomes with faster access and broader availability, it may create a meaningful new market opportunity.

 

 

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