IMDELLTRA
tarlatamab
IMDELLTRA™ is a first-in-class immunotherapy for extensive-stage small cell lung cancer (ES-SCLC), which is difficult to treat and has a poor prognosis. Using Amgen’s bispecific T cell engager (BiTE®) molecules, which are a type of fusion protein, IMDELLTRA engages two targets: CD3 on T cells and DLL3 on the tumor cell. This enables the T cell to recognize and attack the tumor cell leading to its lysis. DLL3 is expressed on the surface of SCLC cells in more than 85% of patients, regardless of chemotherapy treatment, but is minimally expressed on healthy cells, making it an attractive target. Its MOA explains the optimism surrounding IMDELLTRA, and it is expected to be established as the standard of care for previously treated ES-SCLC.
About IMDELLTRA
- Amgen
- DLL3 × CD3-targeting BiTE® molecule
- Biweekly IV infusion to treat adults with extensive-stage SCLC (ES-SCLC) with disease progression on or after platinum-based chemotherapy
- Also being evaluated for other cancer indications, including neuroendocrine prostate cancer
- ~81K new cases of relapsed or refractory (second- and later-line) ES-SCLC in the G7 markets in 2024
Why is it a drug to watch?
SCLC is an aggressive malignancy characterized by rapid, uncontrolled cell growth and early onset of metastases. The treatment landscape for relapsed or refractory SCLC is currently dominated by chemotherapy, which has a median OS of only about 5 months, indicating a significant unmet need.
The exceptional efficacy outcomes of the phase 2 DeLLphi-301 trial of IMDELLTRA led to the U.S. FDA granting it accelerated approval
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ORR: 40%
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Median DOR: 9.7 months
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Median PFS: 4.9 months (median follow-up of 10.6 months)
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Median OS: 14.3 months (median follow-up of 10.6 months)
The updated data from the DeLLphi-301 study after a follow-up of 16.6 months presented during World Conference on Lung Cancer (WCLC) 2024 provided further evidence to support the approval of IMDELLTRA for patients with relapsed or refractory SCLC with disease progression on or after platinum-based chemotherapy:
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Median OS: 15.2 months (median follow-up of 20.7 months)
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6-month OS rate: 73.4%
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Median PFS: 4.3 months
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ORR: 40%
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CR: 3%
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PR: 37%
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Median DOR: 9.7 months
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Median DCR: 70%
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AEs leading to dose-reduction: 16%
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AEs leading to treatment discontinuation: 4%
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At least grade 3 CRS: 4%
Additional phase 3 trials are ongoing for confirmatory purposes and label expansion:
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DeLLphi-304: adults with second-line SCLC who have relapsed after platinum-based first-line chemotherapy (confirmatory trial for regular approval of IMDELLTRA for relapsed or refractory SCLC)
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IMDELLTRA vs standard of care (lurbinectedin, topotecan, amrubicin)
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Primary endpoint: OS
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Estimated primary and study completion: July 2027
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DeLLphi-305: adults with first-line ES-SCLC who were treated with first-line induction therapy with IMFINZI® (durvalumab; AstraZeneca) plus chemotherapy
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First-line extensive-stage SCLC after first-line induction therapy with IMFINZI and chemotherapy
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IMDELLTRA in combination with IMFINZI vs IMFINZI monotherapy
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Primary endpoint: OS 7
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Estimated primary completion: September 2027
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Estimated study completion: September 2028
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DeLLphi-306: adults with limited-stage SCLC (LS-SCLC) who have not progressed following concurrent chemoradiotherapy
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IMDELLTRA vs standard of care (lurbinectedin, topotecan, amrubicin)IMDELLTRA vs placebo
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Primary endpoint: PFS
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Estimated primary and study completion: October 2029
Review and approval status
October 2023
Breakthrough therapy designation: U.S. FDA
December 2023
Priority review: U.S. FDA
May 2024
Accelerated approval: U.S. FDA
Actual and expected launch:
- 2024: United States
- 2025: European Union, Japan
- 2027: Mainland China
Patents estimated to expire beginning in 2036
Drug Timeline & Success Rates
Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of October 31, 2024
How will IMDELLTRA impact the market for SCLC?
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The SCLC drug therapy market is expected to grow from $1.7bn in sales in the major markets in 2022 to $5.8bn in 2032 (13% CAGR).
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Growth will partially be driven by a rise in diagnosed incidence cases leading to a larger drug-treatable population from 2022 to 2032 and increased drug treatment rates for previously treated SCLC, with disease relapse and recurrence remaining common features of SCLC. Therefore, second- and third-line drug treatment rates will gradually rise, from approximately 70% to 76% and from 48% to 56%, respectively.
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In addition, the relapsed or refractory patient population is and will remain the most commercially lucrative patient setting in SCLC. It accounts for more than half of all drug-treatable opportunities and will remain the same through 2032. IMDELLTRA is expected to garner huge sales given its approval for the second- or later-line setting.
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For the third-line patient segment, sales are anticipated to grow from $53.0m in 2022 to $817m in 2032, with IMDELLTRA and ifinatamab deruxtecan (Merck and Daiichi Sankyo) significantly contributing to sales in the later lines.
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IMDELLTRA and ifinatamab deruxtecan will help address the substantial unmet need for more efficacious therapies in the later-line setting and provide some diversification to later-line treatment options but will struggle to compete with chemotherapy given their higher cost and hard-to-manage toxicity profile.
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SCLC is highly sensitive to platinum-based chemotherapy, and a systemic chemotherapy regimen is almost always recommended for limited-stage small cell lung cancer (LS-SCLC) and ES-SCLC. However, novel, effective therapies such as IMDELLTRA are expected to experience rapid uptake, especially when positioned as an add-on to current standards of care.
What gaps in treatment does IMDELLTRA fill?
SCLC is an aggressive cancer, with few therapeutic options. Second-line options typically offer a duration of response of just 3.6 to 5.3 months and OS of less than 8 months. LS-SCLC is generally treated with curative intent, while the aims of ES-SCLC treatment are prolonged survival, delayed disease progression and palliation of symptoms. Although ES-SCLC is highly sensitive to chemotherapy, development of resistance is inevitable, and few patients derive benefit from later-line therapy, with many experiencing significant side effects and poor quality of life. The increasing use of immunotherapies in the first-line ES-SCLC has limited their use in second and later lines. Therefore, treatments that extend OS for LS-SCLC and ES-SCLC and effectively fill gaps in the second- and third-line settings are critical needs, which IMDELLTRA has the potential to address.
What hurdles might it need to overcome to reach blockbuster status?
The high number of comorbidities and the disabling effects of the disease itself make many treatments with toxic or severe side effects unsuitable for some patients. The novel agent IMDELLTRA, due to its premium pricing and average per patient cost of $150,500, will find it difficult to compete with chemotherapy, which will remain the standard of care, as well as generic cytotoxic agents. Additionally, the challenging safety profile of IMDELLTRA, particularly the boxed warning for CRS and ICANS, may discourage physicians from prescribing it due to the added complexity of managing these toxicities. Potential future competitors for IMDELLTRA include the emerging DLL3 × CD3 bispecific BI-764532 (Boehringer Ingelheim) and trispecific antibodies MK-6070 (Merck) and RG6524 (Roche), both targeting DLL3, CD3 and CD137. Its use in later-line therapy will also limit IMDELLTRA’s sales, especially due to the short treatment durations that result from rapid disease progression and short survival rates.
