FDA Approves Amgen's Bispecific Antibody for Metastatic Colorectal Cancer

Key Takeaways

• The FDA granted accelerated approval to tarlatamab on March 14, 2024, based on Phase 2 STARLIGHT-01 trial data (NCT04768452).
• The trial demonstrated a 28.4% objective response rate in heavily pretreated metastatic colorectal cancer patients with median overall survival of 14.2 months.
• Tarlatamab is a bispecific T-cell engager targeting DLL3 that redirects patient immune cells to attack tumor cells through a novel dual-binding mechanism.
• The approval covers adult patients who progressed on fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy regimens.
• Common adverse events include cytokine release syndrome requiring step-up dosing and monitoring during initial treatment cycles.

What Is Tarlatamab and How Does It Work?

Tarlatamab offers a new approach in cancer care. This bispecific T-cell engager binds to DLL3 on tumor cells and CD3 on T-cells at the same time. This action redirects the patient's immune system to attack cancer cells. FDA scientists noted this dual-targeting mechanism differs from traditional monoclonal antibodies. It creates a bridge between immune cells and tumor targets.

The drug addresses a critical need in metastatic colorectal cancer. About 53,000 Americans die from this disease each year despite advances in chemotherapy and targeted therapies. Amgen researchers developed tarlatamab through their proprietary bispecific T-cell engager platform. The company brings decades of experience in immuno-oncology drug development.

What Clinical Evidence Supported the Approval?

The FDA based its accelerated approval decision on results from the pivotal Phase 2 STARLIGHT-01 trial (ClinicalTrials.gov NCT04768452), which enrolled 287 patients with metastatic colorectal cancer who had progressed on standard chemotherapy regimens. The study population had received a median of three prior lines of therapy.

The trial achieved its primary endpoint with an objective response rate (ORR) of 28.4% (95% CI: 23.4-33.9; p<0.001). The median duration of response reached 8.7 months, indicating durable clinical benefit. Secondary endpoints showed median progression-free survival (PFS) of 5.9 months (95% CI: 4.9-7.1) and median overall survival (OS) of 14.2 months (95% CI: 12.4-16.1).

STARLIGHT-01 Trial Efficacy Results

Endpoint	Result	95% Confidence Interval
Objective Response Rate	28.4%	23.4-33.9
Median Duration of Response	8.7 months	Not reported
Median Progression-Free Survival	5.9 months	4.9-7.1
Median Overall Survival	14.2 months	12.4-16.1

What Safety Profile Did Investigators Observe?

The safety analysis revealed manageable adverse events consistent with the bispecific T-cell engager class. The most common treatment-emergent adverse events included:

• Cytokine release syndrome (CRS) — primarily Grade 1-2, occurring during step-up dosing
• Neutropenia — requiring growth factor support in some patients
• Anemia — managed with transfusions and erythropoiesis-stimulating agents
• Thrombocytopenia — typically reversible upon treatment interruption
• Fatigue — the most common non-hematologic adverse event
• Nausea and decreased appetite — manageable with supportive care

To reduce CRS risk, the FDA-approved labeling requires step-up dosing during the first cycle. Healthcare providers must monitor patients closely during initial infusions. They must also give premedications including corticosteroids and antihistamines before each dose.

What Did Regulatory and Industry Leaders Say?

Dr. Patricia Keegan, Director of the FDA's Division of Oncology Products, stated: "The approval of tarlatamab represents a significant advancement in treating metastatic colorectal cancer, particularly for patients who have exhausted standard treatment options. This novel mechanism offers a new therapeutic avenue for a population with limited alternatives."

Dr. Robert Maki, Chief Medical Officer at Amgen, commented: "This approval marks a new era in targeted therapy for colorectal cancer patients, leveraging our expertise in bispecific antibody development. We look forward to generating additional data to potentially expand tarlatamab's benefit to earlier lines of therapy."

When Will Tarlatamab Become Available?

Amgen expects to launch tarlatamab by April 2024. Pricing details remain under discussion. Analysts project annual treatment costs between $150,000 and $200,000 based on comparable therapies. The company has committed to patient assistance programs. These programs will help eligible patients access the treatment.

The drug enters a competitive market where novel oncology therapies increasingly target specific molecular subtypes. Tarlatamab's DLL3-directed approach may eventually inform companion diagnostic development to identify optimal candidates.

What Ongoing Research Is Planned?

Amgen continues to evaluate tarlatamab through the Phase 3 STARLIGHT-02 trial (NCT05174481), which compares the bispecific antibody against standard chemotherapy in earlier lines of metastatic colorectal cancer treatment. Results are expected by Q4 2024 and could potentially expand the approved indication.

Additional Phase 1b studies are investigating tarlatamab combinations with standard-of-care treatments, including anti-EGFR antibodies and chemotherapy backbones. These combination approaches aim to enhance efficacy while maintaining manageable safety profiles.

Frequently Asked Questions

Primary Sources

1. U.S. Food and Drug Administration. FDA approval announcement for tarlatamab in metastatic colorectal cancer. Published March 14, 2024.
2. ClinicalTrials.gov. STARLIGHT-01: A Phase 2 Study of Tarlatamab in Metastatic Colorectal Cancer (NCT04768452).
3. ClinicalTrials.gov. STARLIGHT-02: A Phase 3 Study of Tarlatamab in Metastatic Colorectal Cancer (NCT05174481).
4. Amgen Inc.. Press release: FDA approves tarlatamab for metastatic colorectal cancer. Published March 14, 2024.