Sotorasib + Panitumumab for Cancer

Recruiting at 203 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Serious infection, Interstitial lung disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 31

Duration: Up to 3 years

105 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of sotorasib, with or without panitumumab, in treating advanced solid tumors with the KRAS G12C mutation. Sotorasib blocks a protein that aids cancer cell growth, while panitumumab (Vectibix) aims to slow or stop tumor growth. The trial includes two groups: one receiving both drugs and another receiving only sotorasib, with the option to switch to the combination if the cancer progresses. Individuals with advanced solid tumors, who have tried standard treatments and possess the KRAS G12C mutation, might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have completed any prior cancer treatment at least 21 days before registration and recovered from any adverse effects. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of sotorasib and panitumumab is generally safe and well-tolerated. In earlier studies with patients who have a specific cancer mutation called KRAS G12C, this treatment was found to be safe, with most patients experiencing only mild side effects.

Serious side effects were rare; for instance, only about 3.2% of patients experienced kidney problems, and very few cases were severe.

Additionally, the FDA has already approved sotorasib for other uses, indicating that its safety is well understood. Doctors have a good understanding of how it works in the body.

Overall, previous studies consider the treatment safe. Participants in trials should still discuss any concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of sotorasib and panitumumab for cancer because it offers a novel approach to treatment. Unlike traditional cancer therapies that often target cancer cells broadly, sotorasib specifically targets the KRAS G12C mutation, a common driver in several cancers that's been notoriously hard to target. Panitumumab, on the other hand, is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), which plays a key role in the growth and spread of cancer cells. By combining these therapies, there’s potential to more effectively halt cancer progression and possibly overcome resistance seen with other treatments. This dual-target strategy is particularly promising for patients with limited options.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors with KRAS G12C mutation?

This trial will evaluate the effectiveness of sotorasib both alone and with panitumumab for treating certain cancers with the KRAS G12C mutation. Research has shown that combining sotorasib with panitumumab yields promising results, helping patients live longer without cancer progression. Specifically, 26.4% of patients with hard-to-treat colorectal cancer experienced tumor shrinkage or disappearance. This indicates that the treatment can halt cancer growth in some individuals. The combination blocks signals that promote cancer cell growth and division, making it a potentially strong option for those with advanced solid tumors. ^{1 3 6 7 8}

Who Is on the Research Team?

Kristen Spencer, MD

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have spread and contain a specific mutation (KRAS G12C). Participants must have tried at least one standard treatment without success, be able to undergo a biopsy, and have good enough health to perform daily activities. They should not have any gastrointestinal issues that could affect medication absorption.

Inclusion Criteria

I am HIV positive, on effective treatment, and my viral load has been undetectable for 6 months.

I finished my last cancer treatment 21 days ago and have mostly recovered from side effects.

I have not been treated with KRAS G12C and EGFR inhibitors together.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sotorasib orally once daily and panitumumab intravenously on days 1 and 15 of each 28-day cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Visits every 28 days for treatment, with additional visits for blood samples, biopsy, and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 3-6 months for up to 36 months.

Up to 36 months

Follow-up visits every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Panitumumab
• Sotorasib

Trial Overview The study is testing the effectiveness of AMG 510 (sotorasib) alone or combined with panitumumab in treating KRAS G12C mutant solid tumors. Sotorasib aims to stop cancer cells from multiplying by blocking an abnormal protein, while panitumumab targets cancer cell growth.

How Is the Trial Designed?

Group I: Cohort II (sotorasib, panitumumab) Experimental Treatment 6 Interventions

Patients receive combination therapy as in Arm A.

Group II: Cohort I Arm A (sotorasib, panitumumab) Experimental Treatment 6 Interventions

Patients receive sotorasib PO QD on days 1-28 and panitumumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.

Group III: Cohort I Arm B (sotorasib) Active Control 5 Interventions

Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.

Panitumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Vectibix for:

• Metastatic colorectal cancer (mCRC) with wild-type KRAS

Approved in United States as Vectibix for:

• Metastatic colorectal cancer (mCRC) with wild-type KRAS

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Panitumumab, when combined with chemotherapy, significantly prolongs progression-free survival in patients with wild-type KRAS metastatic colorectal cancer, but shows no overall survival benefit in second-line treatment.

In patients with mutant KRAS tumors, panitumumab is less effective, leading to shorter progression-free survival compared to chemotherapy alone, highlighting the importance of KRAS mutation status in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab: a review of its use in metastatic colorectal cancer. Keating, GM.[2021]

Panitumumab, approved for treating metastatic colorectal cancer, significantly improved progression-free survival (PFS) compared to best supportive care alone, with median PFS times of 56 days versus 51 days, respectively, in a study of 463 patients.

While panitumumab showed efficacy in delaying disease progression, it did not improve overall survival, and common side effects included skin rash and hypomagnesemia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: panitumumab (Vectibix). Giusti, RM., Shastri, KA., Cohen, MH., et al.[2018]

Sotorasib (LUMAKRAS™) is an innovative treatment specifically targeting KRAS G12C mutations in solid tumors, particularly effective for non-small cell lung cancer (NSCLC) and colorectal cancer.

In May 2021, sotorasib received accelerated approval from the US FDA for adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have undergone at least one prior treatment, marking a significant milestone in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib: First Approval. Blair, HA.[2022]

Sotorasib is a first-in-class oral medication that specifically targets the KRAS G12C mutation in non-small cell lung cancer (NSCLC), showing a clinically relevant objective response rate in patients during the CodeBreaK 100 trial.

The drug has a manageable safety profile, allowing for dose adjustments to handle any side effects, making it a valuable treatment option for patients with advanced KRAS G12C mutation-positive NSCLC who have already undergone other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. Lee, A.[2022]

In the phase II CodeBreak 100 trial, the KRASG12C inhibitor sotorasib showed promising efficacy, with over one-third of patients with non-small cell lung cancer responding to the treatment.

Patients treated with sotorasib experienced a median progression-free survival of nearly 7 months, supporting its potential as a significant therapeutic option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib Edges Closer to Approval. [2021]

Panitumumab (Vectibix) was evaluated in a trial with 463 patients suffering from advanced colorectal cancer, showing a mean progression-free survival (PFS) of 96 days compared to 60 days for those receiving only best supportive care, indicating a significant benefit in delaying disease progression.

Despite the improvement in PFS and an objective response rate of 8%, there was no difference in overall survival between the treatment groups, leading to accelerated approval by the FDA with the requirement for further confirmation of clinical benefit for full approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Giusti, RM., Shastri, K., Pilaro, AM., et al.[2020]

In a study of 31 patients with KRAS G12C mutated non-small cell lung cancer (NSCLC) treated with sotorasib, 32% experienced grade 3 or higher hepatotoxicity, typically occurring around 51 days after starting treatment.

The risk of hepatotoxicity was significantly higher in patients who had received prior immune checkpoint inhibitors (ICIs) within 90 days, with none of the patients without prior ICI exposure developing hepatotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time from immune checkpoint inhibitor to sotorasib use correlates with risk of hepatotoxicity in non-small cell lung cancer: A brief report. Desai, A., Rakshit, S., Bansal, R., et al.[2023]

Sotorasib, used as a third-line therapy, showed significant efficacy in a patient with KRAS G12C-mutated lung cancer, improving performance status and reversing disseminated intravascular coagulation (DIC) within two weeks.

The treatment led to the disappearance of multiple brain metastases, suggesting that sotorasib may be a viable option for patients with poor performance status and active brain metastases, although the benefits were temporary due to the emergence of new liver metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Response to Sotorasib of a Patient With KRAS G12C-Mutated Lung Cancer With Cancer-Associated Disseminated Intravascular Coagulation: A Case Report. Kunimasa, K., Tamiya, M., Inoue, T., et al.[2023]

In three clinical trials involving patients with metastatic colorectal cancer, the addition of panitumumab to standard chemotherapy did not significantly affect the quality of life (QoL) of patients, despite the occurrence of skin toxicities.

Patients experiencing severe skin toxicity (grade ≥3) had a similar impact on QoL as those with milder skin toxicity (grade <3), indicating that the severity of skin reactions did not correlate with worse QoL outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin toxicity and quality of life during treatment with panitumumab for RAS wild-type metastatic colorectal carcinoma: results from three randomised clinical trials. Koukakis, R., Gatta, F., Hechmati, G., et al.[2019]

In a phase 2 study involving 148 patients with metastatic colorectal cancer, panitumumab demonstrated a 9% overall response rate and a median progression-free survival of 14 weeks, indicating its efficacy as a treatment option for patients who had previously failed other therapies.

Panitumumab was generally well tolerated, with manageable side effects; 95% of patients experienced skin toxicity, but only 5% had severe reactions, suggesting that while dermatologic issues are common, they are not typically severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Hecht, JR., Patnaik, A., Berlin, J., et al.[2018]

Panitumumab is a human monoclonal antibody that targets the epidermal growth factor receptor (EGFR), which plays a crucial role in the growth and spread of cancer cells, specifically in metastatic colorectal carcinoma.

It is used as a single-agent treatment for patients whose cancer has progressed after standard chemotherapy regimens, including fluoropyrimidine, oxaliplatin, and irinotecan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab (vectibix). Gemmete, JJ., Mukherji, SK.[2021]

Panitumumab, an anti-EGFR monoclonal antibody, significantly improves progression-free survival when combined with chemotherapy in patients with wild-type KRAS metastatic colorectal cancer, but shows no overall survival benefit in second-line treatment.

In patients with mutant KRAS tumors, panitumumab is less effective, leading to shorter progression-free survival when combined with certain chemotherapy regimens, highlighting the importance of KRAS mutation status in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on panitumumab in metastatic colorectal cancer. Keating, GM.[2018]

Sotorasib, a KRASG12C inhibitor approved for treating advanced KRASG12C-mutated non-small cell lung cancer (NSCLC), has shown promising results in a patient with untreated brain metastases, leading to a complete resolution of neurological symptoms.

This case suggests that sotorasib may have intracranial activity, but further studies are necessary to better understand its effectiveness and response duration in patients with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remarkable Intracranial Response to Sotorasib in a Patient With KRAS G12C-Mutated Lung Adenocarcinoma and Untreated Brain Metastases: A Case Report. Yeh, J., Marks, JA., Alzeer, AH., et al.[2022]

Citations

1. amgen.com amgen.com/newsroom/press-releases/2025/01/fda-approves-lumakras-sotorasib-in-combination-with-vectibix-panitumumab-for-chemorefractory-kras-g12cmutated-metastatic-colorectal-cancer

FDA APPROVES LUMAKRAS® (SOTORASIB) IN ... Study results demonstrated that LUMAKRAS 960 mg daily plus Vectibix (n=53) showed an improved median PFS of 5.6 months (4.2, 6.3) compared to 2 ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308795

Sotorasib plus Panitumumab in Refractory Colorectal ... Overall survival data are maturing. The objective response was 26.4% (95% CI, 15.3 to 40.3), 5.7% (95% CI, 1.2 to 15.7), and 0 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/pubmed/37870968/

Sotorasib plus Panitumumab in Refractory Colorectal ... Overall survival data are maturing. The objective response was 26.4% (95% CI, 15.3 to 40.3), 5.7% (95% CI, 1.2 to 15.7), and 0 ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-02026

Overall Survival Analysis of the Phase III CodeBreaK 300 ... In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator's choice.

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer

FDA approves sotorasib with panitumumab for KRAS ... Additional efficacy outcome measures included overall survival (OS), overall response rate (ORR), and duration of response (DOR). The study ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11135132/

Sotorasib with panitumumab in chemotherapy-refractory ... Sotorasib-panitumumab demonstrated acceptable safety with promising efficacy in chemotherapy-refractory KRAS G12C-mutated metastatic CRC.

7. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00352-3/fulltext

Health-related quality of life in patients with KRAS G12C ... In conclusion, the combination of sotorasib 960 mg and panitumumab not only significantly improved clinical outcomes but also resulted in better ...

8. lumakrashcp.com lumakrashcp.com/mcrc/safety

Safety & Adverse Events - LUMAKRAS® (sotorasib) In 126 patients receiving Vectibix® in combination with sotorasib across clinical studies, acute renal failure occurred in 3.2%, including Grade 3 (0.8%).