Sotorasib + Panitumumab for Cancer

Recruiting at 177 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

Trial Summary

What is the purpose of this trial?

This phase II ComboMATCH treatment trial tests how well AMG 510 (sotorasib) with or without panitumumab works in treating patients with KRAS G12C mutant solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Sotorasib is in a class of medications called KRAS inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells. Panitumumab is in a class of medications called monoclonal antibodies. It works by slowing or stopping the growth of cancer cells. Giving combination panitumumab and sotorasib may kill more tumor cells in patients with advanced solid tumors with KRAS G12C mutation.

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.

What data supports the idea that Sotorasib + Panitumumab for Cancer is an effective drug?

The available research shows that Sotorasib, when used alone, has shown promising results in treating non-small cell lung cancer (NSCLC) with a specific mutation called KRAS G12C. In clinical trials, more than a third of patients responded positively to the drug, and it helped control the disease for nearly 7 months on average. Additionally, there are case reports where Sotorasib helped improve symptoms in patients with brain metastases and other complications. While the research does not specifically mention the combination of Sotorasib with Panitumumab, the effectiveness of Sotorasib in treating certain cancers suggests potential benefits when used in combination with other treatments. ^{1 2 3 4 5}

What safety data is available for the treatment with Sotorasib and Panitumumab?

Sotorasib, also known as Lumakras, has been evaluated for safety in patients with KRAS G12C mutation-positive non-small cell lung cancer (NSCLC). It has a manageable tolerability profile, with dose modifications allowed to manage toxicity. Hepatotoxicity has been noted as a risk, especially when used after immune checkpoint inhibitors. Panitumumab, used for RAS wild-type metastatic colorectal cancer, is associated with skin toxicities that can impact quality of life. Safety data from multiple trials indicate these are characteristic side effects of epidermal growth factor receptor inhibitors like Panitumumab. ^{1 3 6 7 8}

Is Panitumumab a promising drug for cancer treatment?

Panitumumab is a promising drug for treating certain types of cancer, especially metastatic colorectal cancer. It works well for patients with a specific type of tumor called wild-type KRAS. When used with chemotherapy, it can help slow down the progression of the disease, giving patients more time before the cancer gets worse. It has been approved by the FDA for use in patients whose cancer has not responded to other treatments. ^{9 10 11 12 13}

Research Team

Kristen Spencer, MD

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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]

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 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]

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, 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, 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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Sotorasib Edges Closer to Approval. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Sotorasib: First Approval. [2022]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Rapid Response to Sotorasib of a Patient With&#160;KRAS G12C-Mutated Lung Cancer With&#160;Cancer-Associated Disseminated Intravascular Coagulation: A Case Report. [2023]

6. England 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. [2023]

7. Netherlands 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. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Panitumumab (vectibix). [2021]

10. New Zealand pubmed.ncbi.nlm.nih.gov

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

11. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on panitumumab in metastatic colorectal cancer. [2018]

12. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: panitumumab (Vectibix). [2018]

13. United States 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. [2020]