Sotorasib + Panitumumab for Cancer
Recruiting in Palo Alto (17 mi)
+167 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Disqualifiers: Serious infection, Interstitial lung disease, Pregnancy, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
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.
12345What 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.
13678Is 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.
910111213Eligibility 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.
+32 more
Trial 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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Group I: Cohort II (sotorasib, panitumumab)Experimental Treatment6 Interventions
Patients receive combination therapy as in Arm A.
Group II: Cohort I Arm A (sotorasib, panitumumab)Experimental Treatment6 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 Control5 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic in FloridaJacksonville, FL
Advocate Good Shepherd HospitalBarrington, IL
Advocate Illinois Masonic Medical CenterChicago, IL
AMG Crystal Lake - OncologyCrystal Lake, IL
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. [2022]Sotorasib (LUMAKRAS™ in the USA and LUMYKRAS™ in the EU) is an orally active, first-in-class G12C-mutant KRAS (KRASG12C) inhibitor. By binding irreversibly to KRASG12C, sotorasib inhibits downstream signalling pathways which are associated with cell growth and differentiation. Sotorasib is indicated for the treatment of adults with advanced, previously treated, KRAS G12C mutation-positive non-small cell lung cancer (NSCLC) in multiple countries, including the countries of the EU and the USA. A clinically relevant objective response rate was observed in patients with KRAS G12C mutation-positive NSCLC during the primary analysis and in an updated analysis of the phase I/II CodeBreaK 100 trial. Furthermore, a clinically relevant response duration was reported in updated analyses of the trial. Sotorasib has a manageable tolerability profile, with permitted dose modifications to manage toxicity. In summary, sotorasib is a promising KRASG12C inhibitor that increases the available treatment options for patients with KRAS G12C mutation-positive NSCLC who were previously treated with platinum-based chemotherapy and/or immunotherapy.
Sotorasib Edges Closer to Approval. [2021]The KRASG12C inhibitor sotorasib continues to impress in non-small cell lung cancer: In the phase II CodeBreak 100 trial, the agent elicited responses in more than a third of patients and led to a median progression-free survival of almost 7 months. Based on these results, Amgen has filed for the drug's approval with the FDA and the European Medicines Agency.
Sotorasib: First Approval. [2022]Sotorasib (LUMAKRAS™) is a RAS GTPase family inhibitor being developed by Amgen for the treatment of solid tumours with KRAS mutations, including non-small cell lung cancer (NSCLC) and colorectal cancer. In May 2021, sotorasib was granted accelerated approval by the US FDA for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. This article summarizes the milestones in the development of sotorasib leading to this first approval for KRAS G12C-mutated NSCLC.
Remarkable Intracranial Response to Sotorasib in a Patient With KRAS G12C-Mutated Lung Adenocarcinoma and Untreated Brain Metastases: A Case Report. [2022]Sotorasib is a KRAS G12C inhibitor that recently received approval for use in locally advanced or metastatic KRAS G12C-mutated NSCLC. CodeBreaK100, the phase 2 clinical trial leading to the approval of sotorasib, excluded patients with untreated brain metastases; there have been no reports describing efficacy of sotorasib on untreated brain metastases. We present a case of a patient with active untreated brain metastases with resulting disorientation and weakness who has radiographic response and complete resolution of neurologic symptoms with sotorasib. Our case illustrates the intracranial activity of sotorasib, but additional studies are needed to characterize the intracranial response rate and duration of response in these patients.
Rapid Response to Sotorasib of a Patient With KRAS G12C-Mutated Lung Cancer With Cancer-Associated Disseminated Intravascular Coagulation: A Case Report. [2023]The efficacy of sotorasib for patients with KRAS G12C-mutated lung cancer with poor performance status (PS) and active brain metastases remains unknown. Here, we present a case in which sotorasib was introduced as the third-line therapy for a patient whose PS worsened due to active multiple brain metastases and disseminated intravascular coagulation (DIC) caused by rapid tumor progression; a marked effect was observed. DIC and PS improved two weeks after the start of the administration, and multiple brain metastases disappeared. The effect lasted only approximately four months due to the development of a new liver metastasis, but sotorasib improved PS and the DIC status was reversed, allowing for further treatment. Sotorasib could be considered for introduction in patients with poor PS.
Time from immune checkpoint inhibitor to sotorasib use correlates with risk of hepatotoxicity in non-small cell lung cancer: A brief report. [2023]We evaluated the risk factors and outcomes for patients who experienced hepatotoxicity after use of sotorasib in KRAS G12C mutated NSCLC.
Skin toxicity and quality of life during treatment with panitumumab for RAS wild-type metastatic colorectal carcinoma: results from three randomised clinical trials. [2019]Epidermal growth factor receptor inhibitors such as panitumumab are associated with characteristic skin toxicities. We summarise data from three panitumumab clinical trials to investigate the potential impact of skin toxicity on quality of life (QoL) in patients with metastatic colorectal cancer (mCRC).
Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. [2018]The safety and efficacy of the fully human antibody panitumumab was evaluated in patients with metastatic colorectal cancer refractory to available therapies.
Panitumumab (vectibix). [2021]Panitumumab (Vectibix), is a human monoclonal antibody EGFR antagonist indicated as a single agent for the treatment of metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy regimens. This article will present the mechanism of action as well as the clinical role for this monoclonal antibody.
Panitumumab: a review of its use in metastatic colorectal cancer. [2021]Panitumumab (Vectibix(R)) is a recombinant, fully human, IgG2 anti-epidermal growth factor receptor (EGFR) monoclonal antibody. This article reviews the clinical efficacy of intravenous panitumumab in combination with chemotherapy in the first- and second-line treatment of metastatic colorectal cancer and as monotherapy in chemotherapy-refractory metastatic colorectal cancer, as well as summarizing its pharmacological properties and tolerability. Panitumumab is indicated for use in patients with wild-type rather than mutant KRAS tumours. The efficacy of intravenous panitumumab 6 mg/kg administered every 2 weeks was examined in randomized, open-label, multicentre, phase III trials in patients with metastatic colorectal cancer. When administered as first- or second-line treatment in combination with chemotherapy, panitumumab plus chemotherapy prolonged progression-free survival to a significantly greater extent than chemotherapy alone in patients with wild-type KRAS tumours; no significant between-group difference in overall survival was seen in the second-line treatment trial. In patients with mutant KRAS tumours, progression-free survival was significantly shorter with panitumumab plus oxaliplatin-based chemotherapy than with oxaliplatin-based chemotherapy alone in the first-line treatment trial, with no significant difference between patients receiving panitumumab plus irinotecan-based chemotherapy (FOLFIRI) and those receiving FOLFIRI alone in the second-line treatment trial. In chemotherapy-refractory patients with metastatic colorectal cancer, panitumumab monotherapy plus best supportive care prolonged progression-free survival to a significantly greater extent than best supportive care alone in both the overall population and in patients with wild-type KRAS tumours, but not in those with mutant KRAS tumours; there was no significant between-group difference in overall survival. Panitumumab has an acceptable tolerability profile when administered as monotherapy or in combination with chemotherapy. It is associated with the skin-related toxicities characteristic of EGFR inhibitors and appears to have a low risk of immunogenicity. In conclusion, in patients with wild-type KRAS tumours, panitumumab is a useful option in combination with chemotherapy for the first- and second-line treatment of metastatic colorectal cancer or as monotherapy for the treatment of chemotherapy-refractory metastatic colorectal cancer.
Spotlight on panitumumab in metastatic colorectal cancer. [2018]Panitumumab (Vectibix) is a recombinant, fully human, IgG2 anti-epidermal growth factor receptor (EGFR) monoclonal antibody. This spotlight reviews the clinical efficacy of intravenous panitumumab in combination with chemotherapy in the first- and second-line treatment of metastatic colorectal cancer and as monotherapy in chemotherapy-refractory metastatic colorectal cancer, as well as summarizing its pharmacologic properties and tolerability. Panitumumab is indicated for use in patients with wild-type rather than mutant KRAS tumors. The efficacy of intravenous panitumumab 6 mg/kg administered every 2 weeks was examined in randomized, open-label, multicenter, phase III trials in patients with metastatic colorectal cancer. When administered as first- or second-line treatment in combination with chemotherapy, panitumumab plus chemotherapy prolonged progression-free survival to a significantly greater extent than chemotherapy alone in patients with wild-type KRAS tumors; no significant between-group difference in overall survival was seen in the second-line treatment trial. In patients with mutant KRAS tumors, progression-free survival was significantly shorter with panitumumab plus oxaliplatin-based chemotherapy (FOLFOX4) than with FOLFOX4 alone in the first-line treatment trial, with no significant difference between patients receiving panitumumab plus irinotecan-based chemotherapy (FOLFIRI) and those receiving FOLFIRI alone in the second-line treatment trial. In chemotherapy-refractory patients with metastatic colorectal cancer, panitumumab monotherapy plus best supportive care prolonged progression-free survival to a significantly greater extent than best supportive care alone in both the overall population and in patients with wild-type KRAS tumors, but not in those with mutant KRAS tumors. Intravenous panitumumab has an acceptable tolerability profile when administered as monotherapy or in combination with chemotherapy. It is associated with the skin-related toxicities characteristic of EGFR inhibitors and appears to have a low risk of immunogenicity. In conclusion, in patients with wild-type KRAS tumors, panitumumab is a useful option in combination with chemotherapy for the first- and second-line treatment of metastatic colorectal cancer or as monotherapy for the treatment of chemotherapy-refractory metastatic colorectal cancer.
FDA drug approval summary: panitumumab (Vectibix). [2018]On September 27, 2006, the U.S. Food and Drug Administration granted approval to panitumumab (Vectibix, Amgen, Inc., Thousand Oaks, CA) for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Panitumumab approval is based on the results of a single, open-label, randomized, multinational study that enrolled 463 patients with EGFR-expressing (at least 1+ membrane staining in > or =1% of tumor cells) metastatic colorectal cancer. Patients were randomized to either best supportive care (BSC) alone or BSC plus panitumumab, 6 mg/kg i.v., every other week. The primary study endpoint was progression-free survival (PFS), determined by an independent review committee that was blinded as to treatment assignment. BSC patients who progressed were eligible to receive panitumumab. The study patients' median age was 62 years, with 40% aged > or =65; 63% were male, 99% were white, 86% had a baseline Eastern Cooperative Oncology Group performance status score of 0 or 1, and 67% had colon cancer. The median time from diagnosis of metastases was approximately 19 months and the median number of prior therapies was 2.4. The PFS duration was significantly longer among patients randomized to receive panitumumab in addition to BSC (n = 231) compared with BSC alone (n = 232). The median and mean PFS times were 56 and 96.4 days, respectively, for patients receiving panitumumab and 51 and 59.7 days, respectively, for patients receiving BSC alone. Nineteen partial responses (8%, 95% confidence interval [CI], 5.3%-12.5%) were observed in panitumumab treated patients. The median duration of response was 17 weeks (95% CI, 16-25 weeks). Approximately 75% of patients in the BSC alone arm crossed over to receive panitumumab after disease progression. There was no difference in overall survival between the two study arms. The most common adverse events were skin rash, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea. The most serious adverse events were pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, diarrhea, and constipation.
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]To describe the Food and Drug Administration review and marketing approval considerations for panitumumab (Vectibix) for the third-line treatment of patients with epidermal growth factor receptor-expressing metastatic colorectal carcinoma.