On June 4, 2023 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported detailed results from the Phase 3 confirmatory MIRASOL trial (GOG 3045/ENGOT OV-55) evaluating the safety and efficacy of ELAHERE (mirvetuximab soravtansine-gynx) compared to chemotherapy in patients with folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer (PROC) (Press release, ImmunoGen, JUN 4, 2023, View Source [SID1234632421]). The results are being presented by Dr. Kathleen Moore in a late-breaking oral abstract session today at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois. These data have also been selected for the 2023 Best of ASCO (Free ASCO Whitepaper) program, which will be held this summer following the ASCO (Free ASCO Whitepaper) Annual Meeting.

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"I am thrilled to share these impressive results from the confirmatory MIRASOL trial at ASCO (Free ASCO Whitepaper), which further demonstrate the potential of ELAHERE to become the new standard of care for patients with FRα-positive PROC," said Kathleen Moore, Associate Director of Clinical Research and Director of the Oklahoma TSET/Sarah Cannon Phase I Program, Professor of the Section of Gynecologic Oncology at The University of Oklahoma and MIRASOL Principal Investigator. "As we saw in the top-line data announced last month, ELAHERE demonstrated an improvement versus chemotherapy across all efficacy endpoints and, importantly, is the first treatment to show an overall survival benefit in this patient population. The 33% reduction in the risk of death, along with the differentiated and well-characterized safety profile seen in MIRASOL, reinforce the potential of ELAHERE to serve as a transformative option for ovarian cancer patients and change how this disease is treated."

MIRASOL is a randomized Phase 3 trial of ELAHERE versus investigator’s choice (IC) of single-agent chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan). Eligibility criteria include patients with PROC whose tumors express high levels of FRα, using the Ventana FOLR1 Assay, and who have been treated with up to three prior regimens. The primary endpoint of this trial is progression-free survival (PFS) by investigator assessment. Key secondary endpoints include objective response rate (ORR) and overall survival (OS).

MIRASOL enrolled 453 patients. Patients were stratified by number of prior lines of therapy (14% had one prior line of therapy, 40% had two prior lines of therapy, and 46% had three prior lines of therapy) and by IC chemotherapy, with paclitaxel as the most commonly chosen (41%), followed by PLD (36%) and topotecan (23%). 62% of patients received prior bevacizumab; 55% received a prior PARP inhibitor. As of the data cutoff on March 6, 2023, the median follow-up time for OS was 13.1 months; 14% of patients on the ELAHERE arm remained on study drug compared to 3% on the IC chemotherapy arm.

ELAHERE demonstrated a statistically significant and clinically meaningful improvement in PFS by investigator assessment compared to IC chemotherapy, with a hazard ratio (HR) of 0.65 (95% confidence interval [CI]: 0.52, 0.81; p<0.0001), which represents a 35% reduction in the risk of tumor progression or death in the ELAHERE arm compared to the IC chemotherapy arm. The median PFS in the ELAHERE arm was 5.62 months (95% CI: 4.34, 5.95) compared to 3.98 months (95% CI: 2.86, 4.47) in the IC chemotherapy arm.
ELAHERE demonstrated a statistically significant and clinically meaningful improvement in OS compared to IC chemotherapy. With 204 OS events reported as of March 6, 2023, the median OS was 16.46 months (95% CI: 14.46, 24.57) in the ELAHERE arm, compared to 12.75 months (95% CI: 10.91, 14.36) in the IC chemotherapy arm, with a HR of 0.67 (95% CI: 0.50, 0.89; p=0.0046). This represents a 33% reduction in the risk of death in the ELAHERE arm in comparison to the IC chemotherapy arm.
ORR by investigator assessment in the ELAHERE arm was 42.3% (95% CI: 35.8%, 49.0%), including 12 complete responses (CRs), compared to 15.9% (95% CI: 11.4%, 21.4%), with no CRs, in the IC chemotherapy arm.
In addition to data on the primary and key secondary endpoints, further safety and efficacy analyses from MIRASOL will be presented:

In the bevacizumab-naïve subset (n=172), the PFS HR was 0.66, (95% CI: 0.46, 0.94; p=0.0210); in the bevacizumab-pretreated subset (n=281), the PFS HR was 0.64 (95% CI: 0.49, 0.84; p=0.0011).
In the bevacizumab-naïve subset, the OS HR was 0.51 (95% CI: 0.31, 0.86; p=0.0099); in the bevacizumab-pretreated subset, the OS HR was 0.74 (95% CI: 0.54, 1.04; p=0.0789).
PFS and ORR results by blinded independent central review (BICR) were concordant with investigator assessment.
The HR for PFS by BICR was 0.72 (95% CI: 0.56, 0.92; p=0.0082).
ORR by BICR in the ELAHERE arm was 36.1% (95% CI: 29.9, 42.7), including 16 complete responses (CRs), compared to 14.6% (95% CI: 10.3, 19.9), with 4 CRs, in the IC chemotherapy arm.
ELAHERE was well-tolerated, consistent with the known safety profile seen in the broader development program. No new safety signals were identified in MIRASOL.
Compared with IC chemotherapy, ELAHERE was associated with lower rates of grade 3 or greater treatment-emergent adverse events (TEAEs) (42% vs 54%) and serious adverse events (24% vs 33%).
Dose delays due to TEAEs occurred in 54% of patients on both arms; dose reductions due to TEAEs occurred in 34% of ELAHERE treated patients vs 24% of IC chemotherapy patients; discontinuations due to TEAEs occurred in 9% of ELAHERE treated patients vs 16% of IC chemotherapy patients.
The safety profile of ELAHERE consists of predominantly low-grade ocular and gastrointestinal TEAEs.
Detailed safety data will be presented, including rates of all grade and grade 3+ ocular, gastrointestinal, neuropathy, and hematologic TEAEs for ELAHERE vs IC chemotherapy (paclitaxel, PLD, topotecan).
"We are incredibly pleased the MIRASOL results were selected as a late-breaking presentation at ASCO (Free ASCO Whitepaper)," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "As the first novel therapy to extend overall survival in platinum-resistant disease, and with consistent efficacy regardless of prior bevacizumab use, ELAHERE is a much-needed advance in the ovarian cancer treatment paradigm. We look forward to submitting the MAA and sBLA for ELAHERE in the EU and US, respectively, during the second half of the year, and to progressing the broader ELAHERE development program as we work to deliver this biomarker-directed ADC to eligible patients."

In November 2022, the US Food and Drug Administration (FDA) granted accelerated approval for ELAHERE for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens based on ORR and duration of response data from the pivotal SORAYA trial.

LATE-BREAKING ORAL PRESENTATION
Title: Phase III MIRASOL (GOG 3045/ENGOT-ov55) Study: Initial Report of Mirvetuximab Soravtansine vs. Investigator’s Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers with High Folate Receptor-Alpha Expression
Presenter: Dr. Kathleen Moore, Associate Director of Clinical Research and Director of the Oklahoma TSET/Sarah Cannon Phase I Program, Professor of the Section of Gynecologic Oncology at The University of Oklahoma and MIRASOL Principal Investigator
Session: Late-Breaking Abstract Session: Presentation and Discussion of LBA5507
Date: Sunday, June 4, 2023
Time: 7:30 am to 8:05 am CT / 8:30 am to 9:05 am ET

POSTER PRESENTATIONS
ImmunoGen is also presenting two trial-in-progress posters at ASCO (Free ASCO Whitepaper).

Title: GLORIOSA: A Randomized, Open-Label, Phase 3 Study of Mirvetuximab Soravtansine with Bevacizumab vs. Bevacizumab as Maintenance in Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Presenter: Dr. David O’Malley, Professor, Director of Gynecologic Oncology at the Ohio State University and the James Cancer Center
Abstract: TPS5622
Poster Board: 312a

Title: A Phase 1b/2 Study of Pivekimab Sunirine in Combination with Venetoclax/Azacitidine or Magrolimab for Patients with CD123-Positive Acute Myeloid Leukemia
Presenter: Dr. Naval Daver, Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center
Abstract: TPS7073
Poster Board: 203a

Additional information can be found at www.asco.org.

ABOUT OVARIAN CANCER
Ovarian cancer is the leading cause of death from gynecological cancers in the US. Each year, roughly 20,000 patients are diagnosed, and 13,000 patients will die. Most patients present with late-stage disease and will typically undergo surgery followed by platinum-based chemotherapy. Unfortunately, the majority of patients eventually develop platinum-resistant disease, which is difficult to treat. In this setting, standard of care single-agent chemotherapies are associated with low response rates, short durations of response, and significant toxicities.

ABOUT ELAHERE
ELAHERE (mirvetuximab soravtansine-gynx) is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells.

Indication and Usage
ELAHERE is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Important Safety Information
BOXED WARNING: OCULAR TOXICITY

ELAHERE can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis.
Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.
Administer prophylactic artificial tears and ophthalmic topical steroids.
Withhold ELAHERE for ocular toxicities until improvement and resume at the same or reduced dose.
Discontinue ELAHERE for Grade 4 ocular toxicities.
WARNINGS and PRECAUTIONS
Ocular Disorders
ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.

Ocular adverse reactions occurred in 61% of patients with ovarian cancer treated with ELAHERE. Nine percent (9%) of patients experienced Grade 3 ocular adverse reactions, including visual impairment, keratopathy/keratitis (corneal disorders), dry eye, photophobia, and eye pain; and one patient (0.2%) experienced Grade 4 keratopathy. The most common (≥5%) ocular adverse reactions were visual impairment (49%), keratopathy (36%), dry eye (26%), cataract (15%), photophobia (13%), and eye pain (12%).

The median time to onset for first ocular adverse reaction was 1.2 months (range: 0.03 to 12.9). Of the patients who experienced ocular events, 49% had complete resolution and 39% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade) at last follow up. Ocular adverse reactions led to permanent discontinuation of ELAHERE in 0.6% of patients.

Premedication and use of lubricating and ophthalmic topical steroids eye drops during treatment with ELAHERE are recommended. Advise patients to avoid use of contact lenses during treatment with ELAHERE unless directed by a healthcare provider.

Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.

Monitor for ocular toxicity and withhold, reduce, or permanently discontinue ELAHERE based on severity and persistence of ocular adverse reactions.

Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease, including pneumonitis, can occur in patients treated with ELAHERE. Pneumonitis occurred in 10% of patients treated with ELAHERE, including 0.8% with Grade 3 events, and 1 patient (0.2%) with a Grade 4 event. One patient (0.2%) died due to respiratory failure in the setting of pneumonitis and lung metastases.

Monitor patients for pulmonary signs and symptoms of pneumonitis. Infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations.

Withhold ELAHERE for patients who develop persistent or recurrent Grade 2 pneumonitis until symptoms resolve to ≤ Grade 1 and consider dose reduction. Permanently discontinue ELAHERE in all patients with Grade 3 or 4 pneumonitis. Patients who are asymptomatic may continue dosing of ELAHERE with close monitoring.

Peripheral Neuropathy (PN)
PN occurred in 36% of patients with ovarian cancer treated with ELAHERE across clinical trials; 2% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (19%), peripheral sensory neuropathy (9%), paraesthesia (6%), neurotoxicity (3%), hypoaesthesia (2%), peripheral motor neuropathy (1%), neuralgia (0.4%), polyneuropathy (0.2%) and oral hypoesthesia (0.2%).

Monitor patients for signs and symptoms of neuropathy. For patients experiencing new or worsening PN, withhold dosage, dose reduce, or permanently discontinue ELAHERE based on the severity of PN.

Embryo-Fetal Toxicity
Based on its mechanism of action, ELAHERE can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (DM4) and affects actively dividing cells.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ELAHERE and for 7 months after the last dose.

ADVERSE REACTIONS
Serious adverse reactions occurred in 31% of patients. The most common (≥2%) serious adverse reactions were intestinal obstruction (8%), ascites (4%), infection (3%), and pleural effusion (3%). Fatal adverse reactions occurred in 2% of patients, including small intestinal obstruction (1%) and pneumonitis (1%).

Permanent discontinuation of ELAHERE due to adverse reactions occurred in 11% of patients. The most common (≥2%) adverse reactions leading to permanent discontinuation were intestinal obstruction (2%) and thrombocytopenia (2%). One patient (0.9%) permanently discontinued ELAHERE due to visual impairment (unilateral decrease to BCVA < 20/200 that resolved to baseline after discontinuation).

Dosage delays of ELAHERE due to an adverse reaction occurred in 39% of patients. Adverse reactions which required dosage delays in ≥3% of patients included visual impairment (15%), keratopathy (11%), neutropenia (6%), dry eye (5%), cataracts (3%) and increased gamma-glutamyltransferase (3%).

Dose reductions of ELAHERE due to an adverse reaction occurred in 20% of patients. Adverse reactions which required dose reductions in ≥3% of patients included visual impairment (9%) and keratopathy (7%).

The most common (≥20%) adverse reactions, including laboratory abnormalities, were vision impairment, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase, dry eye, decreased magnesium, decreased leukocytes, decreased neutrophils, and decreased hemoglobin.

DRUG INTERACTIONS
Strong CYP3A4 Inhibitors
DM4 is a CYP3A4 substrate. Concomitant use of ELAHERE with strong CYP3A4 inhibitors may increase unconjugated DM4 exposure, which may increase the risk of ELAHERE adverse reactions. Closely monitor patients for adverse reactions with ELAHERE when used concomitantly with strong CYP3A4 inhibitors.

USE IN SPECIAL POPULATIONS
Lactation
Advise women not to breastfeed during treatment with ELAHERE and for at least 1 month after the last dose.

Pediatric Use
Safety and effectiveness of ELAHERE have not been established in pediatric patients.

Hepatic Impairment
Avoid use of ELAHERE in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN).

Please see full Prescribing Information, including Boxed Warning for ELAHERE.

On June 4, 2023 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported results from 24 patients enrolled in its Phase 2, single arm mechanism of action study of trilaciclib administered as a single agent to patients with early-stage triple-negative breast cancer (TNBC) prior to receiving trilaciclib and neoadjuvant therapy (Press release, G1 Therapeutics, JUN 4, 2023, View Source [SID1234632419]). These results highlight the potential for trilaciclib to enhance long term immune surveillance by increasing T cell function and generation of certain memory T cells and demonstrate gene expression profiles that may be associated with improved clinical outcome. These data support earlier findings from this Phase 2 trial demonstrating an increase in the ratio of CD8+ T cells to regulatory T cells (Tregs); a high ratio of CD8+ T cell to Tregs is predictive of overall survival (OS) and is associated with pathologic complete response (pCR). As expected, high rates of pCR were observed in patients with PD-L1(+) tumors and in patients with inflamed tumor immune microenvironments.

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Data generated across multiple preclinical and clinical studies to date show that trilaciclib has the greatest effect on longer term endpoints including OS rather than earlier efficacy measures such as objective response rate (ORR), pCR, and progression free survival (PFS), consistent with other immunotherapies like checkpoint inhibitors. These results suggest that this is likely due to trilaciclib’s immune-mediated mechanism of action that protects the immune system from damage caused by cytotoxic therapy and enhances long-term immune surveillance by increasing the generation of certain memory T cells. This dual benefit may provide important longer-term benefits for patients by improving their ability to generate robust immune responses, particularly when treated with future subsequent therapies.

"Trilaciclib is a highly active molecule that enhances T cell activation, favorably alters the tumor microenvironment, and improves long term immune surveillance; these new immune analyses help identify potential correlates of treatment response and extend our understanding of the mechanism," said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. "Trilaciclib drives increases in certain memory T cells which are important for longer term outcomes like overall survival, consistent with our understanding of the mechanism of action of trilaciclib."

These results are being presented today at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The poster, titled, "Neoadjuvant Single-Dose Trilaciclib Prior To Combination Chemotherapy in Patients with Early Triple-Negative Breast Cancer: Safety, Efficacy, And Immune Correlate Data from a Phase 2 Study," can be found here.

Patient Demographics

As of the data cut date of April 3, 2023, all patients (N = 24) had received a median (range) of 16 (3–16) cycles of treatment; 21 (87.5%) patients received pembrolizumab, and 21 (87.5%) patients received carboplatin, per investigator discretion. All patients completed the study; five underwent definitive surgery prior to completing planned study treatment. At diagnosis, 79% of patients had stage II tumors and 88% had ductal carcinoma; 38% of patients had PD-L1+ tumors, consistent with early TNBC.

Tumor immune microenvironment status was determined at baseline. All participants with immune-desert tumor microenvironments at baseline had PD-L1(-) tumors; an additional nine participants with immune-excluded tumor microenvironments had PD-L1(-) tumors. All participants with immune-inflamed tumor microenvironments at baseline had PD-L1(+) tumors; an additional five participants with immune-excluded tumor microenvironments had PD-L1(+) tumors. Data published by G1 and others show that trilaciclib can promote trafficking of immune cells out of the stroma and into the tumor microenvironment via chemokine release, thus leading to an inflamed tumor immune microenvironment status.

Baseline Correlates of Clinical Outcome: Pathologic Complete Response (pCR)

Tumor infiltrating lymphocytes (TIL) infiltration is associated with better outcomes with trilaciclib. In this mechanism of action trial, the pCR rate is higher (77.8%) in patients with PD-L1(+) tumors relative to that of the overall enrolled patient population. The pCR rate in the overall enrolled population (41.7%) is comparable to that of standard neoadjuvant therapy in this population of patients. As anticipated, the pCR rate was higher in patients with an immune-inflamed tumor microenvironment (75.0%) than those with immune-excluded (35.7%) or immune desert (33.3%) tumor microenvironments.

The tumor status of four enrolled patients converted from PD-L1(-) at baseline to PD-L1(+) after trilaciclib monotherapy (day 7); 50% of these patients achieved pCR during the study.

Immunomodulatory Effects of Trilaciclib

Trilaciclib was shown to enhance the number and function of CD8+ T cells in the tumor microenvironment. Seven days after monotherapy with trilaciclib, the number of CD8+ T cells and GZMB+ cells, which is a surrogate marker for T cell function, were enhanced with statistical significance in patients achieving a pCR. There was also an increase in stromal TILs within the tumor microenvironment after a single dose of trilaciclib.

RNA-sequence analysis revealed 59 genes that were differentially expressed seven days after single-dose trilaciclib in patients who achieved pCR, compared to those who did not. Furthermore, assessment of signaling pathways associated with pCR revealed significant enrichment in pathways associated with immune modulation including T cell receptor signaling and cytokine-cytokine receptor interaction that were not observed at baseline. Key genes associated with memory T cells – SELL (CD62L), IL-7R, and TCF7 – increased from baseline to Day 7, and a subset analysis based on pCR status revealed significant increases in these genes when individually assessed and as a gene signature among patients who achieved pCR.

These results help confirm the role of trilaciclib in increasing the pool of functional memory T cells that could contribute to long-term immune surveillance and efficacy, as measured by longer term endpoints like OS.

Safety Results (n=24)

Trilaciclib continues to show a strong tolerability profile. Trilaciclib in combination with anthracycline (doxorubicin)/ cyclophosphamide/paclitaxel (AC/T) ± pembrolizumab ± carboplatin in the neoadjuvant setting for early-stage TNBC has a similar safety and tolerability profile as standard neoadjuvant regimens. The most common treatment-related adverse events (TRAEs; any grade) related to any study drug were fatigue, nausea, alopecia, and neutropenia/neutrophil count decreased. There were no adverse events leading to discontinuation of trilaciclib.

Trilaciclib Phase 2 Mechanism of Action Trial Design

Tumor tissue was obtained at baseline prior to study drug administration. Patients then received a single dose of monotherapy (240 mg/m2) trilaciclib, followed by a tumor biopsy approximately one week later to assess the ability of a single dose of trilaciclib monotherapy to favorably alter the tumor microenvironment. Paired tumor biopsies were available for 22 patients. Patients then entered the treatment phase in which trilaciclib is administered on day 1 of each cycle of anthracycline/cyclophosphamide for four cycles followed by trilaciclib administered on day 1 of each weekly cycle of taxane chemotherapy for 12 cycles. Pembrolizumab and/or carboplatin was added at the discretion of the investigator. Three to five weeks after the treatment phase, patients had definitive surgery and a final tumor tissue sample was collected if the patient has residual disease. pCR was assessed at definitive surgery by a local pathologist, per the current American Joint Committee on Cancer staging system .

The primary objective was to evaluate the immune-based mechanism of action of a single dose of trilaciclib as measured by the change in the ratio of CD8+ T cells to Tregs in the tumor microenvironment. Secondary endpoints include assessment of pCR rate at the time of definitive surgery, and safety of the combination of trilaciclib with neoadjuvant regimen. Exploratory endpoints include assessment of the immune response, and identification of molecular and cellular biomarkers in tumor or blood samples that may be associated with clinical response/resistance, pharmacodynamic activity, and/or the mechanism of action of trilaciclib.

On June 4, 2023 Bristol Myers Squibb (NYSE: BMY) reported four-year follow-up results from the Phase 3 CheckMate -9LA trial demonstrating durable, long-term survival benefits with Opdivo (nivolumab) plus Yervoy (ipilimumab) with two cycles of chemotherapy compared to four cycles of chemotherapy alone in previously untreated patients with metastatic non-small cell lung cancer (NSCLC) (Press release, Bristol-Myers Squibb, JUN 4, 2023, View Source;9LA-Trial-Show-Durable-Long-Term-Survival-with-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-with-Two-Cycles-of-Chemotherapy-for-Patients-with-Metastatic-Non-Small-Cell-Lung-Cancer/default.aspx [SID1234632416]). With a minimum follow-up of 47.9 months, the dual immunotherapy-based combination continued to enhance overall survival (OS), the trial’s primary endpoint, with 21% of patients treated with Opdivo plus Yervoy with two cycles of chemotherapy alive compared to 16% of patients treated with chemotherapy alone at four years (Hazard Ratio [HR] 0.74; 95% Confidence Interval [CI]: 0.63 to 0.87).

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With extended follow-up, the clinically meaningful efficacy benefit of Opdivo plus Yervoy with two cycles of chemotherapy was maintained across secondary endpoints and key subgroups of patients, with benefits more pronounced amongst high unmet need patients with tumor PD-L1 expression <1% and squamous histology:

PD-L1 <1%: Among patients with tumor PD-L1 expression <1%, the OS rate was 23% for those treated with the dual immunotherapy-based combination vs. 13% for chemotherapy alone, representing a 34% reduction in the risk of death (HR 0.66; 95% CI: 0.50 to 0.86).
Squamous histology: Among those with squamous histology, twice the number of patients treated with Opdivo plus Yervoy with chemotherapy were alive at four years compared to those who received chemotherapy alone (20% vs. 10%, respectively). In this group, the dual immunotherapy combination reduced the risk of death by 36% compared to chemotherapy alone (HR 0.64; 95% CI: 0.48 to 0.84).
No new safety signals were observed with Opdivo plus Yervoy with two cycles of chemotherapy with extended follow-up in the CheckMate -9LA trial. These data will be featured in a late-breaking poster presentation (Abstract #LBA9023) at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 4, 2023, from 5:30 – 7:00 p.m. EDT.

"The durable results seen with nivolumab plus ipilimumab with chemotherapy over four years, especially in patients typically facing a poor prognosis, demonstrate the sustained benefits of combining dual immunotherapy with limited chemotherapy for patients with advanced or metastatic non-small cell lung cancer, which remains an incredibly challenging disease to treat," said David P. Carbone, M.D., Ph.D., CheckMate -9LA investigator and Director of the Thoracic Oncology Center at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute. "The data in patients with tumor PD-L1 expression <1% and squamous histology are particularly encouraging, as they show that the combination therapy continues to reduce the risk of death by approximately one-third compared to chemotherapy alone four years following treatment in patient groups historically facing the worst outcomes."

"Cancer treatment is never a one-size-fits-all approach given that patients with thoracic cancers like non-small cell lung cancer have diverse sets of needs. We are committed to researching solutions that work for more patients and can potentially help improve outcomes and fill areas of high unmet need," said Abderrahim Oukessou, M.D., vice president, thoracic cancers development lead, Bristol Myers Squibb. "Our data in lung cancer at ASCO (Free ASCO Whitepaper) 2023 add to the growing body of evidence supporting the potential of our medicines to improve long-term outcomes for patients in both advanced settings and earlier stages of disease, as well as difficult-to-treat patient groups requiring personalized approaches to treatment. The CheckMate -9LA results, which demonstrate sustained efficacy benefits over four years with an Opdivo-based combination, further reinforce our promise to deliver durable options to more patients across varying stages and types of cancer."

Opdivo plus Yervoy-based combinations have shown significant improvements in OS in six Phase 3 clinical trials in five tumors to date: metastatic NSCLC, metastatic melanoma, advanced renal cell carcinoma, malignant pleural mesothelioma and esophageal squamous cell carcinoma.

About CheckMate -9LA

CheckMate -9LA is an open-label, global multi-center, randomized Phase 3 trial evaluating Opdivo (360 mg Q3W) plus Yervoy (1 mg/kg Q6W) combined with chemotherapy (two cycles) compared to chemotherapy alone (up to four cycles followed by optional pemetrexed maintenance therapy if eligible) as a first-line treatment in patients with metastatic non-small cell lung cancer (NSCLC) regardless of PD-L1 expression and histology. Patients in the experimental arm (n=361) were treated with immunotherapy for up to two years or until disease progression or unacceptable toxicity. Patients in the control arm (n=358) were treated with up to four cycles of chemotherapy and optional pemetrexed maintenance (if eligible) until disease progression or unacceptable toxicity. The primary endpoint of the trial was overall survival (OS) in the intent-to-treat (ITT) population. Secondary hierarchical endpoints included progression-free survival (PFS) and overall response rate (ORR), and the study also evaluated efficacy measures according to biomarkers.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Survival rates vary depending on the stage and type of the cancer when diagnosed.

On June 4, 2023 AskAt reported to have received a communication under Rule 71(3) EPC dated May 19, 2023 from the European Patent Office, with which the grant of the European patent is proposed (Press release, AskAt, JUN 4, 2023, View Source [SID1234632415]). This grant of European Patent Application No. 18191714.7 is an EP4 receptor antagonist use patent for the treatment of cancer, particularly for the use of grapiprant in the treatment of epithelial cancer. AskAt’s EP4 receptor antagonist cancer use patent (Filing Date: April 22, 2010) has already been granted in Japan, the United States, Europe, Canada, China, Korea, Mexico, Brazil, Russia, and Hong Kong. This will reinforce the protection of a
patent in Europe.

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On June 4, 2023 Amgen (NASDAQ:AMGN) reported the presentation of new data from the CodeBreaK clinical trial program, the most comprehensive global development program in patients with KRAS G12C-mutated cancers, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 2-6 in Chicago (Press release, Amgen, JUN 4, 2023, View Source [SID1234632414]). The research presented reinforces the efficacy of LUMAKRAS/LUMYKRAS (sotorasib) in advanced non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (mCRC). Additionally, data from SCARLET, an Amgen funded investigator study sponsored by the West Japan Oncology Group, will be presented on June 6 and is the first study to highlight the safety and efficacy of sotorasib in combination with platinum-based chemotherapy for frontline treatment of patients with advanced NSCLC harboring a KRAS G12C mutation.

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"As the leader in KRAS inhibition, Amgen continues to advance the CodeBreaK program by evaluating LUMAKRAS across different indications and combinations to potentially help more people living with KRAS G12C-mutated cancers," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "These data presented at ASCO (Free ASCO Whitepaper) underscore the clinical importance of LUMAKRAS, including the only randomized trial of a KRASG12C inhibitor to show higher intracranial activity compared to chemotherapy, along with data validating our combination treatment approach in metastatic colorectal cancer, where new precision medicine strategies are desperately needed."

Improved CNS Activity in Advanced NSCLC
In the first and only randomized study for any KRASG12C inhibitor, data from a post-hoc analysis of the global Phase 3 CodeBreaK 200 trial included patients with advanced NSCLC and treated/stable central nervous system (CNS) lesions at baseline, as assessed by a blinded independent central review (BICR). In this analysis using a modified exploratory response assessment in neuro-oncology brain metastases (RANO-BM), LUMAKRAS demonstrated delayed time to CNS progression and longer CNS progression-free survival (PFS) compared with docetaxel.

Additionally, the CNS objective response rate (ORR),* an assessment of CNS tumor shrinkage following treatment, was more than double (33.3% vs 15.4%) in patients treated with LUMAKRAS (n= 18) compared to docetaxel (n= 13). The safety profile in this analysis was similar to the CodeBreaK 200 overall population.

"CNS metastases are an unfortunately common complication of KRAS G12C-mutated advanced NSCLC, occurring in about 30–40% of patients," said Melissa L. Johnson, M.D., director of Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology. "In this post-hoc analysis from CodeBreaK 200, sotorasib delayed CNS progression-free survival by more than five months and is a potential clinically meaningful benefit for second-line NSCLC patients with KRAS G12C mutations."

These results will be presented on Sunday, June 4, as a late-breaking abstract in a poster discussion session: Lung Cancer—Non-Small Cell Metastatic, beginning at 4:30 p.m. CDT. (#LBA9016).

*Exploratory post-hoc analysis in patients with stable/treated CNS lesions at baseline, in which measurable lesions were defined per study as CNS lesions ≥10 mm in diameter by BICR using modified RANO-BM Criteria

New NSCLC Biomarker Data from CodeBreaK 200 Show Consistent Clinical Benefit Across Subgroups
In the first randomized, molecularly-defined analysis of a KRASG12C inhibitor versus chemotherapy, LUMAKRAS showed improved PFS over docetaxel, irrespective of PD-L1 expression level, and retained PFS benefit versus docetaxel across key co-alteration subgroups (including STK11, KEAP1, TP53). Collectively, the biomarker data help inform treatment decision making and the ongoing CodeBreaK clinical development program, which explores LUMAKRAS in novel combinations.

These data will be presented on Tuesday, June 6 during an oral abstract session: Lung Cancer–Non-Small Cell Metastatic, from 9:45 a.m.- 12:45 p.m. CDT (Abstract #9008).

Encouraging Safety and Efficacy in Metastatic CRC
Data from the CodeBreaK 101 Phase 1B study, the first reported results for the combination of LUMAKRAS with Vectibix (panitumumab) and FOLFIRI, showed encouraging safety and efficacy in previously-treated KRAS G12C-mutated metastatic CRC.

Among 42 patients evaluable for response, confirmed ORR was 55% (95% CI: 38.7, 70.2), and disease control rate (DCR) was 93% (95% CI: 80.5, 98.5), with responses observed regardless of the number of prior lines of therapy and regardless of progression on prior irinotecan-based therapy. LUMAKRAS plus Vectibix and FOLFIRI combination reported adverse events consistent with those expected for the therapies under study.

"A priority in KRAS G12C-mutated colorectal cancer research is exploring new treatment combinations that can drastically improve response rates attained with current treatments, which can be as low as 2%," said lead investigator, David S. Hong, M.D., professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, Houston. "These results showed encouraging efficacy with sotorasib in combination with panitumumab and FOLFIRI, and importantly showed consistent safety for each product."

These data will be presented on Monday, June 5 during a poster discussion session: Gastrointestinal Cancer—Colorectal and Anal, from 1:15-2:45 p.m. CDT (Abstract #3513.)

More information on Amgen’s abstracts is available on the ASCO (Free ASCO Whitepaper) website.

About LUMAKRAS/LUMYKRAS (sotorasib)

Amgen took on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS/LUMYKRAS, a KRASG12C inhibitor.i LUMAKRAS/LUMYKRAS has demonstrated a positive benefit-risk profile with rapid, deep, and durable anticancer activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation.ii

Amgen is progressing the largest and broadest global KRASG12C inhibitor development program with unparalleled speed and exploring more than 10 sotorasib combination regimens, with clinical trial sites spanning five continents. To date, over 6,500 patients around the world have received LUMAKRAS/LUMYKRAS through the clinical development program and commercial use.

In May 2021, LUMAKRAS was the first KRASG12C inhibitor to receive regulatory approval with its approval in the U.S., under accelerated approval. LUMAKRAS/LUMYKRAS is also approved in the European Union, Japan, United Arab Emirates, South Korea, Hong Kong, Switzerland, Taiwan, Qatar, and in Australia, Brazil, Canada, Great Britain, Singapore, and Israel under the FDA’s Project Orbis. Additionally, Amgen has submitted MAAs in Argentina, Colombia, Kuwait, Macao, Malaysia, Mexico, Russia, Saudi Arabia, Thailand and Turkey.

LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.iii

About Non-Small Cell Lung Cancer and the KRAS G12C Mutation

Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.iv Overall survival rates for NSCLC are improving but remain poor for patients with advanced disease, and 5-year survival is only 9% for those with metastatic disease.v

KRAS G12C is the most common KRAS mutation in NSCLC.vi About 13% of patients with NSCLC harbor the KRAS G12C mutation.[vii] Unmet medical need remains high and treatment options are limited for NSCLC patients with the KRAS G12C mutation whose first-line treatment has failed to work or has stopped working. The outcomes with other approved therapies are suboptimal, with a median progression-free survival of approximately four months following second-line treatment of KRAS G12C-mutated NSCLC.viii

About Advanced Colorectal Cancer and the KRAS G12C Mutation

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide, comprising 10% of all cancer diagnoses.ix It is also the third most commonly diagnosed cancer globally.x

Patients with previously treated metastatic CRC need more effective treatment options. For patients in the third-line setting, standard therapies yield median PFS times of about two months and patients’ response rates are less than 2%.xi,xii

KRAS mutations are among the most common genetic alterations in colorectal cancers, with the KRAS G12C mutation present in approximately 3-5% of colorectal cancers.xiii,xiv,xv

About CodeBreaK 

The CodeBreaK clinical development program for Amgen’s drug sotorasib is designed to study patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers. 

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors.xvi Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline.ii The Phase 2 trial in metastatic colorectal cancer (mCRC) is fully enrolled and results have been published.xvii

CodeBreaK 200, the global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in KRAS G12C-mutated NSCLC completed enrollment of 345 patients. Eligible patients had previously treated, locally advanced and unresectable or metastatic KRAS G12C-mutated NSCLC. The primary endpoint is progression-free survival and key secondary endpoints include overall survival, objective response rate, and patient-reported outcomes.xviii

Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment.xix A Phase 2 randomized study will evaluate sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment (CodeBreaK 201).xx

LUMAKRAS (sotorasib) U.S. Indication

LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

LUMAKRAS (sotorasib) Important U.S. Safety Information

Hepatotoxicity

LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.
Interstitial Lung Disease (ILD)/Pneumonitis

LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.
Most Common Adverse Reactions

The most common adverse reactions occurring in ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.
Drug Interactions

Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS.
If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.
Please see LUMAKRAS full Prescribing Information. 

About Vectibix (panitumumab)

Vectibix is the first fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC.

In June 2017, the FDA approved a refined indication for Vectibix for use in patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) mCRC.

INDICATION AND LIMITATION OF USE

Vectibix is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC): as first-line therapy in combination with FOLFOX, and as monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

Limitation of Use: Vectibix is not indicated for the treatment of patients with RAS mutant mCRC or for whom RAS mutation status is unknown.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: DERMATOLOGIC TOXICITY

Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].

In Study 20020408, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix. The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures.
Monitor patients who develop dermatologic or soft tissue toxicities while on Vectibix for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune- related effects (e.g., Stevens Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix concerning dermatologic toxicity are provided in the product labeling.
Vectibix is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as "RAS."
Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with RAS-mutant mCRC tumors received Vectibix in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix and FOLFOX versus FOLFOX alone.
Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 20080763) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix treatment, periodically during Vectibix treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate.
In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions.
Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix in combination with chemotherapy.
Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix. In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix therapy. Discontinue Vectibix therapy if ILD is confirmed.
In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix versus the risk of pulmonary complications must be carefully considered.
Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix.
Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix for acute or worsening keratitis.
In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix-treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%), and hypomagnesemia (4% vs 0).
NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix-treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix-treated patients. As a result of the toxicities experienced, patients randomized to Vectibix, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy.
Vectibix can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix.
In monotherapy, the most commonly reported adverse reactions (≥ 20%) in patients with Vectibix were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea.
The most commonly reported adverse reactions (≥ 20%) with Vectibix + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (≥ 2% difference between treatment arms) were diarrhea and dehydration.
To see the Vectibix Prescribing Information, including Boxed Warning, visit www.vectibix.com.