At 12 months, CARTITUDE-4 demonstrated a 75.9% progression-free survival, estimated 84.1% survival compared to 83.6% of standard group.¹⁰ The 3-year median follow-up of the pivotal phase 1B/2 CARTITUDE-1 trial that led to cita-cel’s initial approval, demonstrated a median progression-free survival (mPFS) of 34.9 months (47.5% progression free and alive at 36 months); median overall survival (OS) was not reached; however, an estimated 62.9% survival at 36 months was calculated.⁹

On April 4, 2024, based on the results of the phase 3 KarMMa-3 trial, the FDA approved the use of ida-cel as third line following 2 or more prior lines of therapy that contain an IMiD, PI, and an anti-CD38 monoclonal antibody.⁶ KarMMa-3 trial, with a median follow-up of 18.6 months, demonstrated a mPFS of 13.3 months, response rate of 71%, and CR of 39% in the ida-cel arm compared to the standard regimen arm with 4.4 months, 42%, and 5% respectively. ¹¹

At a 2-year median follow-up, KarMMa, the pivotal phase 2 trial that led to the initial FDA approval, demonstrated a total population overall response rate of 73%, CR of 33%, and a median duration of response (mDOR) of 10.9 months.¹² For patients who achieved a CR or better, the mDOR and mPFS were longer at 21.5 and 22.4 months respectively. The dose response relationship seen with ida-cel led to improved outcomes in patients who received higher doses.

On April 5, 2024, the FDA granted an accelerated approval to Enhertu® (fam-trastuzumab deruxtecan, T-Dxd) as second line for adult patients with unresectable or metastatic HER2-positive (IHC3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options.⁴ Unlike other FDA approved tumor agnostic indications in small niche groups, HER2 expression is found in common cancer which represents a significantly larger population.

Efficacy was evaluated in 192 adult patients enrolled in one of three multicenter trials: DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02.⁴ The accelerated approval was based on outcome measures, objective response rate (ORR) and duration of response, in all three trials.

DESTINY-PanTumor02 is an open-label, study of select solid tumors expressing HER2 immunohistochemistry [IHC] 3+ or IHC 2+.¹³ With the exception of pancreatic cancer, all tumor types achieved an overall response with the greatest response seen in patients with higher HER2 expression, IHC 3+ (ORR was 51.4% and median DOR was 19.4 months).

In DESTINY-Lung01 which assessed patients with non-small cell lung cancer, ORR was 52.9% and median DOR was 6.9 months. For DESTINY-CRC02 in colorectal cancer, ORR was 46.9% and DOR was 5.5 months.⁴

This review for the tumor-agnostic indication was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Singapore’s Health Sciences Authority (HSA). The goal is to increase access to cancer therapy and optimize trial design through the establishment of global treatment standards.^4,14

On February 16, 2024, FDA granted accelerated approval to Amtagvi™ (lifileucel), the first and only cellular therapy to receive FDA approval for a solid tumor cancer. It is indicated for the treatment of patients with unresectable advanced melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor. ⁷ CAR-T therapy is cellular therapy and has successfully treated many types of blood cancers, but this drug class has not received an FDA approval for solid tumor treatment, which make up close to 90% of cancers.¹ Lifieucel’s approval is significant because it will bolster the tumor infiltrating lymphocyte (TIL) pipeline that could eventually impact a range of other solid tumor cancers,

Lifileucel is a tumor-derived autologous T cell immunotherapy composed of a patient’s own T cells, a type of cell that helps the immune system fight cancer. To manufacture Amtagvi, a portion of the patient’s tumor tissue is removed during a surgical procedure. The patients’ T cells are separated from the tumor tissue, further replicated, manufactured, then infused back into the same patient.

This accelerated approval was granted based on the ORR of 31.5% and mDOR was not yet reached. The median time to initial response to lifileucel was 1.5 months. Following Amtagvi administration, Aldesleukin (interleukin-2) is administered to promote lymphocyte expansion into cancer fighting cells.⁷ Like CAR T, lifileucel must be administered at authorized treatment centers. The National Comprehensive Cancer Network (NCCN) currently recommends lifileucel as second line or subsequent therapy for metastatic or unresectable disease.

Annual Wholesaler Acquisition Cost (WAC)

Precision medicine allows for the personal delivery of cancer therapy with a strong potential for positive outcomes. Notably, 73% of pipeline oncology drugs utilize precision medicine. As a result, personalized medicine is driving the present and future of cancer therapy pipeline, cost, and outcomes.