Lumakras/Vectibix Combo Offers New Treatment Option for CRC

The FDA recently approved a new combination treatment for a very small population of cancer patients that has dismal survival rates. In response to a Zitter Insights survey, most oncologists said they believe the new treatment will have at least some impact on their prescribing.

On Jan. 16, the FDA gave another approval to Amgen Inc.’s Lumakras (sotorasib) in combination with the company’s Vectibix (panitumumab) for the treatment of adults with KRAS G12C-mutated metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy.

When omitting skin cancers, CRC is the third most common cancer in both men and women in the U.S. About 22% of people have metastatic CRC when they are first diagnosed, and most CRC deaths are due to metastatic disease. The five-year survival rate for metastatic CRC is 14%, compared with 71% for regional disease and 90% for localized disease.

The FDA granted the new application orphan drug designation; its review used the Real-Time Oncology Review pilot program and the Assessment Aid. Recommended dosing of this indication for Lumakras, a tablet, is 960 mg once daily, and for Vectibix, dosing is 6 mg/kg every 14 days via intravenous infusion. Drugs.com lists the price of 90 320 mg Lumakras tablets as more than $22,244 and a 100 mg/5 mL single-dose vial of Vectibix as more than $1,826.

The approval came after the FDA pushed back the original decision date from Oct. 17, 2024, so it could review supplemental information that Amgen submitted.

The agency first granted accelerated approval to Lumakras, an inhibitor of the RAS GTPase family, on May 28, 2021, and Vectibix, an epidermal growth factor receptor (EGFR) antagonist, on Sept. 27, 2006.

With Lumakras’ first approval — which was for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer, as determined by an FDA-approved test, who have received at least one prior systemic therapy — the agent became the first FDA-approved drug to target KRAS mutations, which for a long time were considered to be undruggable.

KRAS mutations are found in more than half of CRC cases, with the KRAS G12C mutation occurring in about 4% of patients, who have worse overall survival than non-G12C mutations. Other KRAS G12C inhibitors have shown initial efficacy but eventual progression of the disease. EGFR inhibitors have long been used in the treatment of metastatic CRC, and several clinical trials are being conducted to understand their use in combination with a KRAS inhibitor.

In the CodeBreaK 300 clinical trial, Lumakras 960 mg daily plus Vectibix showed an improved median progression-free survival (PFS) of 5.6 months compared with 2 months for investigator’s choice of standard of care: either Taiho Oncology, Inc.’s Lonsurf (trifluridine and tipiracil) or Bayer’s Stivarga (regorafenib). In addition, the overall response rate for the Lumakras/Vectibix arm was 26%, while the ORR was 0% for the comparator arm. The final analysis of overall survival was not statistically significant.

“In metastatic colorectal cancer, KRAS mutations are historically associated with worse mortality rates and inferior outcomes compared to non-mutated tumors, and standard treatment options have shown minimal benefit,” said Marwan G. Fakih, M.D., primary study investigator and co-director of the gastrointestinal cancer program at City of Hope. “Designed for dual blockade of KRAS G12C and EGFR pathways, the combination of sotorasib plus panitumumab provides a needed new treatment option to better overcome cancer's escape mechanisms.”

For the Managed Care Oncology Index: Q4 2024, from Nov. 18, 2024, to Dec. 18, 2024, Zitter Insights polled 35 commercial payers covering 117.3 million lives, 28 Medicare payers covering 47.3 million lives, 50 oncologists and 50 practice managers about their management and prescribing of available and pipeline CRC treatments.

AIS Health and Zitter Insights are both divisions of MMIT.

Payers covering 44% of commercial lives said they expected Lumakras to have some impact on currently available CRC treatments, meaning that they didn’t anticipate changing any coverage or tiering but might change utilization management criteria. But payers with 46% of Medicare lives said they expected the drug to have a moderate impact, with no change in coverage but possible changes to tiering and/or utilization management.

Thirty-five percent of all payers said they anticipated Lumakras would have no impact, 26% said some impact, and 32% said a moderate impact. Only 6% said they expected it to have a high impact, and none said they anticipated a very high impact from the drug’s approval.

Oncologists were also divided on Lumakras’ expected impact on their treatment approach for people with CRC, but 22% pointed to a high or very high impact, meaning their approach to treatment for at least a majority of patients likely would change (see infographic).