FDA Oks Sotorasib/Panitumumab in KRAS G12C-Mutant Colorectal Cancer

• The FDA has approved the combination of sotorasib (Lumakras) and panitumumab (Vectibix) for the treatment of patients with previously treated KRAS G12C-mutated metastatic colorectal cancer (CRC).
• The approval is supported by data from the CodeBreaK 300 (NCT05198934) study.
• The combination led to improvements in progression-free survival (PFS) and overall response rate (ORR) vs investigator’s choice of standard of care.

Sotorasib plus panitumumab has been approved by the FDA for the treatment of patients with previously treated CRC harboring a KRAS G12C mutation.¹

Data from the phase 3 CodeBreaK 300 study presented at the 2023 ESMO Congress support this approval. At a median follow-up of 7.8 months, the median PFS in patients treated with sotorasib 960 mg plus panitumumab was 5.6 months (HR, 0.49; 95% CI; 0.30-0.80), and the median PFS in patients treated with sotorasib 240 mg plus panitumumab was 3.9 months (HR, 0.58; 95% CI, 0.36-0.93). Comparatively, the median PFS in patients treated with investigator’s choice of trifluridine and tipiracil or regorafenib (Stivarga) was 2.2 months (95% CI, 1.9-3.9).²

The most common grade 3 or higher treatment-related adverse effects in the combination arm were dermatitis acneiform (960 mg, 11%; 240 mg, 4%), hypomagnesemia (6%; 8%), rash (6%; 2%), and diarrhea (4%; 6%).

In September 2006, the FDA granted approval to panitumumab for the treatment of patients with EGFR-expressing, metastatic CRC with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.³

In May 2021, the granted accelerated approval to sotorasib for the treatment of locally advanced or metastatic KRAS G12C-mutated non–small cell lung cancer that had received at least 1 prior line of therapy, supported by data from the phase 2 CodeBreaK 100 study (NCT03600883).⁴

In October 2023, the FDA’s Oncologic Drug Advisory Committee voted 10 to 2 that the PFS data from CodeBreaK 200 (NCT04303780) could not be reliably interpreted, as the PFS difference between the sotorasib and docetaxel control arms was small, and there was no difference in overall survival.⁵

In December 2023, the FDA issued a complete response letter to the supplemental new drug application of sotorasib, failing to convert the accelerated approval to traditional approval.⁶

REFERENCES:

1. FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer. FDA. January 16, 2025. Accessed January 16, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer

2. Amgen presents new Lumakras® (sotorasib) plus Vectibix® (panitumumab) data in patients with KRAS G12C-mutated metastatic colorectal cancer. News release. Amgen. October 22, 2023. Accessed October 14, 2024. https://tinyurl.com/47njbyjk 

3. Giusti RM, KaushikkumarSA, Cohen MH, et al. FDA drug approval summary: panitumumab (Vectibix). Oncologist. 2007;12(5):577-583. doi:10.1634/theoncologist.12-5-577

4. FDA grants accelerated approval to sotorasib for KRAS G12C mutated NSCLC. News release. FDA. May 28, 2021. Accessed October 14, 2024. https://tinyurl.com/36dvx72f

5. Oncologic Drugs Advisory Committee (ODAC) Meeting. FDA website. October 5, 2023. Accessed October 14, 2024. https://tinyurl.com/5994v6d3

6. Amgen provides regulatory update on status of Lumakras® (sotorasib). News release. Amgen. December 26, 2023. Accessed October 14, 2024. https://tinyurl.com/4ysvxakk