FDA Pushes Back Decision on Sotorasib/Panitumumab in Colorectal Cancer

Microscopic image of colorectal cancer cells - Generated with Google Gemini AI

• The FDA has delayed its decision on the supplemental new drug application (sNDA) of sotorasib (Lumakras) plus panitumumab (Vectibix) for the treatment of chemorefractory metastatic colorectal cancer (CRC) with a KRAS G12C mutation.
• The expected decision date was October 17, 2024.
• The new deadline for action is January 17, 2025.

The FDA’s decision on the sNDA of sotorasib and panitumumab in KRAS G12C-mutated chemorefractory metastatic CRC has been delayed.¹

Comments from Amgen, the sponsor of the sNDA, said the delay was to allow the FDA to review supplemental information that was recently submitted. The new target action date is January 17, 2025.

The sNDA is supported by data from the phase 3 CodeBreaK 300 study presented at the 2023 ESMO Congress. 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

Findings presented at the 2024 ASCO Annual Meeting showed that the study was not powered to detect a statistically significant difference in overall survival (OS); however, there was a trend toward OS improvement in patients receiving the 960-mg dose of sotorasib with panitumumab.³ The median OS was not reached in the sotorasib 960 mg arm, 11.9 months (95% CI, 7.5-not evaluable [NE]) in the sotorasib 240 mg arm, and 10.3 months (range, 7.0-NE) in the investigator’s choice arm. The hazard ratio 0.70 (95% CI, 0.41-1.18) with sotorasib 960 mg plus panitumumab compared with investigator’s choice and 0.83 (95% CI, 0.49-1.39) with sotorasib 240 mg plus panitumumab compared with investigator’s choice.

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

The FDA’s Oncologic Drug Advisory Committee voted in 10 to 2 in October 2023, 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. Wu, L. FDA delays colorectal cancer decision for Amgen's Lumakras, a setback in race with Bristol Myers. News release. Endpoints News. October 17, 2024. Accessed October 18, 2024. https://bit.ly/3BQOTVT

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 18, 2024. https://tinyurl.com/47njbyjk

3. Fakih M, Salvatore L, Esaki T, et al. Overall survival (OS) of phase 3 CodeBreaK 300 study of sotorasib plus panitumumab (soto+pani) versus investigator’s choice of therapy for KRAS G12C-mutated metastatic colorectal cancer (mCRC). J Clin Oncol. LBA3510-LBA3510(2024). doi:10.1200/JCO.2024.42.17_suppl.LBA3510

4. FDA grants accelerated approval to sotorasib for KRAS G12C mutated NSCLC. News release. FDA. May 28, 2021. Accessed October 18, 2024. https://tinyurl.com/36dvx72f

5. Oncologic Drugs Advisory Committee (ODAC) Meeting. FDA website. October 5, 2023. Accessed October 18, 2024. https://tinyurl.com/5994v6d3

6. Amgen provides regulatory update on status of Lumakras® (sotorasib). News release. Amgen. December 26, 2023. Accessed October 18, 2024. https://tinyurl.com/4ysvxakk