GDC-1971 + Osimertinib/Cetuximab for Non-Small Cell Lung Cancer

No longer recruiting at 18 trial locations

Overseen By Reference Study ID Number: GO44272 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Must be taking: EGFR inhibitors

Must not be taking: Chemotherapy, Immunotherapy, Endocrine therapy, others

Disqualifiers: Hepatitis, HIV, Liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new drug, GDC-1971, combined with either osimertinib (a targeted therapy) or cetuximab (an EGFR inhibitor), to treat certain types of lung and colorectal cancers. It aims to determine the right dose and assess the effectiveness of this combination. The trial seeks participants with advanced lung cancer unresponsive to certain treatments or advanced colorectal cancer that progressed after EGFR inhibitor treatments. Participants should not have specific genetic mutations in their cancer. This trial might be suitable for those dealing with these specific conditions and treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking chemotherapy, immunotherapy, biologic therapy, or investigational agents at least 3 weeks before starting the study. Endocrine therapy must be stopped 2 weeks before, except for certain hormonal therapies. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

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

Previous studies have shown osimertinib to be a safe and effective treatment for non-small cell lung cancer (NSCLC). It has been tested in patients with specific genetic mutations without revealing any unexpected safety issues.

Cetuximab, used for colorectal cancer (CRC), has a well-established safety record based on past patient experiences. The FDA has approved it for advanced CRC, and many patients have used it safely.

GDC-1971 is newer and less familiar, as it remains under study. The current study is in its early stages, focusing on determining a safe dose of GDC-1971 when combined with either osimertinib or cetuximab. Safety information is still being gathered and analyzed.

Overall, while osimertinib and cetuximab have established safety records, researchers continue to investigate GDC-1971 to ensure its safety in these combinations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they involve GDC-1971, a promising new drug that is being tested in combination with existing therapies for non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Unlike conventional treatments that primarily target cancer cells directly, GDC-1971 is believed to enhance the effectiveness of other drugs like osimertinib and cetuximab by potentially interfering with specific cancer cell growth pathways. This could lead to more effective treatment outcomes for patients with advanced or metastatic forms of these cancers. Additionally, the combination with established medications like osimertinib for NSCLC and cetuximab for CRC allows researchers to explore synergistic effects that could offer better control over the disease.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer and colorectal cancer?

In this trial, participants with non-small cell lung cancer (NSCLC) will receive a combination of GDC-1971 and osimertinib. Studies have shown that osimertinib effectively treats NSCLC, especially in patients with specific genetic changes, and it works better than some older treatments, particularly for those whose cancer has spread to the brain. Meanwhile, participants with colorectal cancer (CRC) will receive GDC-1971 in combination with cetuximab. Research indicates that cetuximab effectively treats CRC, especially when combined with chemotherapy in patients with certain genetic profiles. Cetuximab is approved for patients without specific mutations and enhances chemotherapy's effects in these cases. The role of GDC-1971 is still under investigation, as researchers test its potential to complement these established treatments in this trial. ^{2 3 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with certain types of advanced lung or colorectal cancer. Participants must have specific genetic mutations, good organ function, and a performance status indicating they can care for themselves. They should not have had recent major surgeries or treatments, no active infections like hepatitis or HIV, and no history of significant heart, liver, or eye disease.

Inclusion Criteria

My cancer does not have EGFR mutations.

I am fully active or can carry out light work.

My colon or rectum cancer has worsened after treatment with an EGFR inhibitor.

Exclusion Criteria

I have had pulmonary fibrosis, organizing pneumonia, or pneumonitis.

I have untreated or active brain metastases needing medication for symptoms.

My cancer has spread to the lining of my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Finding Stage

Participants receive GDC-1971 in combination with either osimertinib or cetuximab to determine the appropriate dose

28-day cycles until disease progression or unacceptable toxicity

Dose Expansion Stage

Participants receive GDC-1971 at the determined dose in combination with either osimertinib or cetuximab to further evaluate safety and activity

28-day cycles until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• GDC-1971
• Osimertinib

Trial Overview The study tests the safety and effectiveness of GDC-1971 when combined with Osimertinib for lung cancer patients or Cetuximab for colorectal cancer patients. It includes an initial phase to find the right dose followed by a phase to see how well it works at that dose.

How Is the Trial Designed?

Group I: Dose-Finding Stage: Non-Small Cell Lung Cancer (NSCLC) Experimental Treatment 2 Interventions

Participants with unresectable, locally advanced or metastatic NSCLC will receive GDC-1971 at an assigned dose, orally, once daily (QD), on Days 1 to 28 of each 28-day cycle in combination with osimertinib, 80 milligrams (mg), orally, QD, on Days 1 to 28 of each cycle until disease progression or unacceptable toxicity.

Group II: Dose-Finding Stage: Colorectal Cancer (CRC) Experimental Treatment 2 Interventions

Participants with metastatic CRC will receive GDC-1971, at an assigned dose, orally, QD, on Days 1 to 28 days of each 28-day cycle in combination with cetuximab, 500 milligrams per square meter (mg/m\^2), given by IV infusion on Days 1 and 15 of each cycle, until disease progression or unacceptable toxicity.

Group III: Dose Expansion Stage: NSCLC Experimental Treatment 2 Interventions

Participants with unresectable, locally advanced or metastatic NSCLC will receive GDC-1971 at a dose determined in the dose finding stage, orally, QD, on Days 1 to 28 of each 28-day cycle in combination with osimertinib, 80 mg, orally, QD, on Days 1 to 28 of each cycle until disease progression or unacceptable toxicity.

Group IV: Dose Expansion Stage: CRC Experimental Treatment 2 Interventions

Participants with metastatic CRC will receive GDC-1971 at a dose determined in the dose finding stage, orally, QD, on Days 1 to 28 of each 28-day cycle in combination with cetuximab, 500 mg/m\^2, given by IV infusion on Days 1 and 15 of each cycle until disease progression or unacceptable toxicity.

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

Approved in United States as Erbitux for:

• Locally or regionally advanced squamous cell carcinoma of the head and neck
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
• BRAF V600E mutation-positive metastatic colorectal cancer

Approved in European Union as Erbitux for:

• Squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor, which plays a crucial role in the growth of various cancers.

It received accelerated approval from the US FDA in February 2004 for treating metastatic colorectal cancer based on positive tumor response rates observed in Phase II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab. Goldberg, RM.[2020]

Combining osimertinib with either selumetinib or cetuximab significantly improved treatment response rates in EGFR-mutated non-small cell lung cancer (NCLC) models, achieving response rates of 50% to 90% and median progression-free survival times of up to 28 weeks.

The study identified that resistance to these combination therapies is linked to Hedgehog pathway activation, suggesting that targeting this pathway alongside EGFR inhibition could enhance treatment efficacy in resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Efficacy of Dual Blockade of EGFR Signaling by Osimertinib in Combination With Selumetinib or Cetuximab in Activated EGFR Human NCLC Tumor Models. Della Corte, CM., Ciaramella, V., Cardone, C., et al.[2022]

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, has shown repeated effectiveness in treating a patient with nonresectable squamous cell skin cancer, which is significant given the poor prognosis of advanced cases.

This case suggests that cetuximab could be a valuable treatment option for patients with squamous cell carcinomas that express the epidermal growth factor receptor, particularly in palliative care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous squamous cell carcinoma responding serially to single-agent cetuximab. Suen, JK., Bressler, L., Shord, SS., et al.[2022]

Osimertinib significantly improves disease-free survival (DFS) in adults with completely resected, early-stage EGFR mutation-positive non-small cell lung cancer (NSCLC), as shown in the pivotal ADAURA trial, regardless of prior adjuvant chemotherapy.

The treatment is well tolerated with a manageable safety profile, and it does not negatively impact health-related quality of life, making it a suitable option for adjuvant therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. Frampton, JE.[2022]

The Phase III NeoADAURA study is designed to evaluate the effectiveness of neoadjuvant osimertinib, an advanced EGFR inhibitor, in combination with chemotherapy compared to chemotherapy alone in patients with resectable stage II-IIIB N2 EGFR mutation-positive non-small-cell lung cancer (NSCLC).

The primary goal of the study is to assess the major pathological response at the time of surgery, while also examining secondary outcomes such as event-free survival and overall survival, ensuring a comprehensive evaluation of osimertinib's safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA. Tsuboi, M., Weder, W., Escriu, C., et al.[2022]

In the ADAURA study, adjuvant osimertinib significantly improved disease-free survival in patients with resected stage IB to IIIA EGFR-mutated non-small cell lung cancer (NSCLC) compared to placebo, with a median treatment duration of 35.8 months for osimertinib versus 25.1 months for placebo.

After three years of treatment, osimertinib showed no new safety concerns, and patients maintained their health-related quality of life, indicating that osimertinib is both effective and tolerable for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Safety, Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial. John, T., Grohé, C., Goldman, JW., et al.[2023]

Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, was effective for 2.5 years in a 78-year-old woman with T790M-positive lung cancer, but she eventually experienced disease progression due to the emergence of a new resistance mutation (C797G).

The case highlights the potential of liquid biopsy and next-generation sequencing to monitor clonal evolution and identify novel resistance mechanisms in patients treated with osimertinib, which could inform future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquired EGFR C797G Mutation Detected by Liquid Biopsy as Resistance Mechanism After Treatment With Osimertinib: A Case Report. DE Carlo, E., Schiappacassi, M., Pelizzari, G., et al.[2022]

In a post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.

The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

Citations

1. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/lung-cancer/study-to-evaluate-the-safety--pharmacokinetics--and-act-84477.html

Clinical trial for Colorectal Cancer (CRC), Non-Small Cel... The main purpose of the study is to evaluate the safety of GDC-1971 in combination with either osimertinib or cetuximab. The study consists of a dose ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04449874

NCT04449874 | A Study to Evaluate the Safety, ... This is a Phase I dose-escalation and dose-expansion study that will evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26398184/

Cost-Effectiveness of Cetuximab as First-line Treatment for ... Our analysis of FIRE-3 data suggests that first-line treatment with cetuximab and FOLFIRI in KRAS (and extended RAS) WT mCRC patients may improve health ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30218345/

An Update of Efficacy and Safety of Cetuximab in ... Cetuximab is approved for the first-line treatment in combination with chemotherapy or as a single agent in patients who have failed or are intolerant to ...

5. news.bms.com news.bms.com/news/details/2012/FDA-Approves-ERBITUXR-cetuximab-as-First-Line-Treatment-in-KRAS-Mutation-Negative-Wild-Type-Epidermal-Growth-Factor-Receptor-EGFR-Expressing-Metastatic-Colorectal-Cancer-in-Combination-with-FOLFIRI-Irinotecan-5-Fluorouracil-Leucovorin/default.aspx

FDA Approves ERBITUX(R) (cetuximab) as First-Line ... ERBITUX is not indicated for the treatment of KRAS mutation-positive colorectal cancer. Concurrently, the FDA also approved the first KRAS ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05954871

NCT05954871 | Study to Evaluate the Safety, ... Participants with metastatic CRC will receive GDC-1971, at an assigned dose, orally, QD, on Days 1 to 28 days of each 28-day cycle in combination with cetuximab ...

7. anzctr.org.au anzctr.org.au/Trial/Registration/TrialReview.aspx?id=21601&isClinicalTrial=True

ANZCTR - Registration GDC-1971 capsules or tablets will be administered as specified in each treatment arm. Treatment: Drugs: Osimertinib Osimertinib tablets will be ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/125084s273lbl.pdf

ERBITUX (cetuximab) - accessdata.fda.gov The data described below reflect exposure to ERBITUX in 242 patients with K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer (mCRC) [see Warnings ...