Caroline Seymour

TAR-200 led to an 82.4% complete response rate in BCG-unresponsive, high-risk non-muscle invasive bladder cancer with CIS, data from SunRISe-1 showed.

Among patients with Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary disease, treatment with TAR-200 — an intravesical chemotherapy releasing system — elicited high complete response rates, according to data from the phase 2b SunRISe-1 study.

These data were shared during the 2025 American Urological Association Annual Meeting, where investigators highlighted data from Cohort 2 of the trial which evaluated 85 patients within this population. Patients who received TAR-200 achieved an overall complete response rate of 82.4% and the 12-month complete response rate was 45.9%.

The Kaplan-Meier–estimated 12- and 24-month complete response rates were 52.4% and 44.7%, respectively. The median time to onset of complete response was 2.8 months and 95.7% of patients achieved a complete response within the first three months. The complete response rate was consistent across patient subgroups.

“The standard of care for [patients with] BCG-unresponsive, high-risk NMIBC is radical cystectomy,” Dr. Joseph Jacob, an associate professor of urology at Upstate University Hospital in Syracuse, New York, said during the presentation. “Radical cystectomy is a life changing operation with considerable morbidity and up to an 8% 90-day mortality rate. Unfortunately, many patients are unable or unwilling to undergo radical cystectomy. There are limited FDA-approved treatment options in patients with BCG-unresponsive, high-risk NMIBC.”

TAR-200 is a novel drug releasing system that employs an intravesical drug releasing application which provides sustained delivery of gemcitabine in the bladder. In December 2023, TAR-200 received breakthrough therapy designation from the FDA for the treatment of adult patients with BCG-unresponsive, high-risk NMIBC who are ineligible for or have declined radical cystectomy. Then in January 2025, a new drug application (NDA) was submitted to the FDA seeking the approval of the agent for the treatment of patients with BCG-unresponsive, high-risk NMIBC with CIS, regardless of the presence of papillary tumors.

Radical cystectomy: removal of the whole bladder; this can include removal of the prostate and seminal vesicles or the uterus, ovaries, fallopian tubes and part of the vagina.

Complete response rate: the disappearance of all target lesions.

Carcinoma in situ (CIS): a group of abnormal cells.

Papillary disease: thin, finger-like cancerous tumors that usually start in the bladder lining and extend into the center of the bladder.

Additional findings from SunRISe-1 displayed that the median duration of response was 25.8 months. High-risk NMIBC recurrence was observed in 32.9% of responders and 5.7% experienced at least T2 disease progression. The 12-month cystectomy-free rate was 86.6%. The estimated 12- and 24-month duration of response probabilities were 56.2% and 51.8%, respectively. The 12-month duration of response rate was 52.9% and 47.1% of responses were ongoing at the data cutoff.

In terms of safety, most treatment-emergent side effects (TRAE) in cohort 2 were grade 1 (mild) or 2 (moderate) and resolved after a median of 3.1 weeks. Five patients experienced at least 1 serious treatment-related side effect and 3.5% of patients discontinued TAR-200 monotherapy due to treatment-related side effect. There were no treatment-related deaths.

Any-grade and grade 3 (severe) or higher treatment-related side effects occurred at rates of 83.5% and 12.9%, respectively. The most common any-grade TRAEs included pollakiuria (43.5%), dysuria (40%), and micturition urgency (24.7%). Grade 3 or higher treatment-related side effects consisted of urinary tract pain (4.7%), bladder pain (2.4%), and urinary tract infection (1.2%).

“Health-related quality of life remained high [during] TAR-200 treatment and TAR-200 monotherapy was well tolerated with rare serious TRAEs and treatment discontinuation,” Jacob said in conclusion. “TAR-200 is under review by the FDA following the submission of a NDA.”

Cohorts 1,2 and 3 of SunRISe-1 enrolled adult patients with histologically confirmed high-risk NMIBC with CIS with or without papillary disease with an ECOG performance status of 2 or less. Patients were also required to have persistent or recurrent disease within 12 months of completion of BCG therapy and be unresponsive to BCG therapy with no plans to undergo a radical cystectomy. Cohort 4 consisted of patients with papillary-only high-risk NMIBC without CIS.

In cohort 1, patients received TAR-200 in combination with cetrelimab and those in cohorts 2 and 3 received TAR-200 or cetrelimab monotherapy, respectively. Patients in cohort 4 also received TAR-200 monotherapy. TAR-200 was administered once every three weeks for the first 24 weeks then every 12 weeks through week 96 of treatment.

In cohorts 1, 2 and 3, the primary end point was overall complete response rate. Key secondary end points consisted of duration of response, overall survival, safety, tolerability and health-related quality of life. In cohort 4, the primary end point was disease-free survival.

At baseline, the median age in cohort 2 was 71 years. Most patients were male, White, former nicotine users, had an ECOG performance status of 0, and had CIS-only disease. The median number of prior doses of BCG was 12 and the median time from last receipt of BCG to CIS diagnosis was 3.2 months.

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Articles

TAR-200, an intravesical chemotherapy releasing system, demonstrated high complete response rates in patients with BCG-unresponsive, high-risk non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), according to the phase 2b SunRISe-1 study. The study reported an 82.4% overall complete response rate and a 45.9% 12-month complete response rate. The treatment was well-tolerated, with most side effects being mild or moderate. TAR-200 received FDA breakthrough therapy designation and is under review for approval for patients ineligible for or declining radical cystectomy.

TAR-200 showed high complete response rates in BCG-unresponsive, high-risk non-muscle invasive bladder cancer with CIS in the phase 2b SunRISe-1 study.

TAR-200 Shows High Response Rates in Bladder Cancer Subset

Bavencio plus best supportive care improves survival outcomes in advanced urothelial carcinoma, regardless of diabetes status.

Among patients with advanced urothelial carcinoma, first-line maintenance treatment with Bavencio (avelumab) plus best supportive care (BSC) prolonged overall survival (OS) and progression-free survival (PFS) versus BSC, regardless of diabetes mellitus status, according to exploratory analyses from the phase 3 JAVELIN Bladder 100 trial.

, which showed that in the subgroup of patients with diabetes mellitus, those who received Bavencio plus BSC (55 patients) achieved a median OS of 20.8 months versus 14.5 months with BSC alone. At two years, OS rates were 44.5% and 34.1%, respectively. At three years, OS rates were 33.1% and 20.3%, respectively. Among patients without diabetes, median OS was 24.7 months with Bavencio plus BSC versus 15.8 months with BSC alone. The two-year OS rates were 50.7% and 39.4%, respectively. The three-year OS rates were 36.6% and 31.9%.

Similarly, PFS was prolonged in both patient subgroups. In those with diabetes, median PFS was 5.6 months with Bavencio plus BSC versus 2 months with BSC alone. At two years, PFS rates were 18.5% and 9.2%, respectively. At three years, PFS rates were 13.5% and 5.5%, respectively. In patients without diabetes, median PFS was 5.4 months with Bavencio plus BSC versus 2.1 months with BSC alone. The 2-year PFS rates were 24.3% and 6.5%, respectively. The 3-year PFS rates were 16.3% and 5.3%, respectively.

Best supportive care (BSC): the optimal level of care provided to a patient.

Overall survival (OS): the average length of time that patients are alive after starting treatment or being diagnosed.

Progression-free survival (PFS): the amount of time a patient lives with a disease without it worsening.

Lipase: an enzyme that helps digest fats in food.

Amylase: an enzyme that breaks down carbohydrates, like starches, into simple sugars.

“Overall, these results show that Bavencio frontline maintenance is associated with long-term efficacy benefits and consistent safety in patients with advanced urothelial carcinoma with or without diabetes mellitus who are progression free after first-line platinum-based chemotherapy,” explained lead study author Dr. Shilpa Gupta, director of Genitourinary Medical Oncology at the Cleveland Clinic Taussig Cancer Institute in Ohio.

Background and Design of the JAVELIN Bladder 100 Trial

The trial included patients with unresectable locally advanced or metastatic urothelial carcinoma who remained progression free following 4 to 6 cycles of first-line platinum-based chemotherapy. Patients were assigned to receive frontline maintenance with Bavencio plus BSC or BSC alone. The exploratory analysis assessed long-term efficacy and safety outcomes in subgroups of patients with or without documented diabetes mellitus at randomization.

At a data cutoff of June 4, 2021, with at least two years of follow-up, median OS was significantly prolonged in the Bavencio plus BSC cohort compared with BSC alone, at 23.8 months versus 15.0 months, respectively.Similarly, median PFS was 5.5 months in the Bavencio arm versus 2.1 months in the BSC alone arm, demonstrating the clinical benefit of Bavencio maintenance therapy in this setting.

Results also demonstrated the long-term safety of Bavencio maintenance therapy, with health-related quality of life preserved throughout treatment. These results contributed to the inclusion of Bavencio frontline maintenance in updated international guidelines as a recommended treatment option for patients with advanced urothelial carcinoma.

Additionally, the study explored the effects of diabetes mellitus, a known risk factor for bladder cancer that is more prevalent in older adults. Previous research has suggested that diabetes may be associated with reduced efficacy of immunotherapy in some cancers; however, data in urothelial carcinoma remain limited. As a result, this post hoc exploratory analysis from JAVELIN Bladder 100 was conducted to assess outcomes in subgroups of patients with or without diabetes mellitus at randomization.

Baseline Patient Characteristics of JAVELIN Bladder 100 Post Hoc Analysis

Baseline demographics and disease characteristics were assessed by diabetes mellitus status, and median follow-up was at least 38 months in both treatment arms.

The median age among patients with diabetes mellitus was 70 years (range, 51-86) in the Bavencio plus BSC arm and 72 years (range, 57-89) in the BSC alone arm. Among patients without diabetes mellitus, the median age was 68 years (range, 37-90) with Bavencio and 69 years (range, 32-85) with BSC alone. Most patients were male in both diabetes subgroups (87.3% and 91.5% with Bavencio and BSC alone in the diabetes cohort, respectively, and 73.9% and 75.9% in the non-diabetes cohort).

Most patients were enrolled from Europe. Smaller proportions were from North America, Asia, and Australasia.

In the diabetes subgroup, 52.7% of patients in the Bavencio arm and 32.2% in the BSC arm were PD-L1 positive. Among patients without diabetes, 54.2% and 51.5% were PD-L1 positive in the Bavencio and BSC arms, respectively.

In the Bavencio plus BSC arm, grade 3 or greater treatment-related side effects (TRSEs) were reported in 24.1% (13 patients) of patients with diabetes and 18.6% (54 patients) of those without diabetes. The most common grade 3 of higher TRSEs were increased lipase, amylase and anemia. In the BSC alone arm, 1.7% of patients in both subgroups experienced any-grade TRSEs.

Serious side effects (SEs) occurred in 37.0% of patients with diabetes and 29.3% of those without diabetes receiving Bavencio. Among these, 9.3% and 10.3%, respectively, were classified as serious TRSEs. In the BSC alone group, 23.7% of patients with diabetes and 20.3% of those without diabetes experienced serious SEs, and no serious TRSEs were reported.

Bavencio discontinuation due to TRSEs occurred in 11.1% of patients with diabetes and 14.8% of those without diabetes, with 9.3% and 12.1% of cases directly attributed to TRSEs. TRSEs leading to death were rare, occurring in 1.9% of patients with diabetes and 2.1% of those without diabetes in the Bavencio group.

Immune-related SEs (irSEs) were observed in 31.5% (17 patients) of patients with diabetes and 32.4% (94 patients) of those without diabetes treated with Bavencio, compared with 3.4% and 1.4% of patients in the BSC alone group.

The most commonly reported TRSEs of any grade in the Bavencio plus BSC arm included pruritus (11.1% versus 15.5% in the diabetes and non-diabetes cohorts, respectively), hypothyroidism (7.4% versus 11.7%), fatigue (5.6% versus 11.7%), and asthenia (9.3% versus 10.7%). Gastrointestinal-related TRSEs, including diarrhea (7.4% versus 11.0%) and nausea (9.3% versus 6.9%), were also frequently observed.

“Avelumab first-line maintenance (1LM) in patients (pts) with advanced urothelial carcinoma (aUC) with or without diabetes mellitus (DM): long-term outcomes from JAVELIN Bladder 100,” By Dr. Shipla Gupta, et al. 

“Avelumab first-line maintenance for advanced urothelial carcinoma: results from the JAVELIN Bladder 100 trial after ≥2 years of follow-up,” by Dr. Thomas Powles, et al. 

First-line maintenance treatment with avelumab (Bavencio) plus best supportive care (BSC) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with advanced urothelial carcinoma, regardless of diabetes mellitus status. The JAVELIN Bladder 100 trial demonstrated prolonged OS and PFS in both diabetic and non-diabetic subgroups, with consistent safety profiles. The study's findings have led to the inclusion of avelumab in international guidelines as a recommended treatment option. The trial also explored the impact of diabetes, a known risk factor for bladder cancer, on treatment efficacy.

Patients with advanced urothelial carcinoma had prolonged survival with Bavencio and BSC treatment, regardless of diabetes mellitus status.

Bavencio and BSC Extends Survival in Bladder Cancer, Regardless of Diabetes Status

Patient-reported outcomes were similar for Fotivda with or without Opdivo in advanced clear cell RCC: © stock.adobe.com

Adding Fotivda (tivozanib) to Opdivo (nivolumab) was shown to have comparable patient-reported outcomes (PROs) versus Fotivda monotherapy for the treatment of locally advanced or metastatic clear cell renal cell carcinoma (RCC) whose disease progressed on one or two systemic therapies and at least one immune checkpoint inhibitor (ICI), according to results from the phase 3 TiNivo-2 study.

Patient-reported outcomes: reports on a patient’s health condition that come directly from the patient themselves

Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index-Disease-Related Symptoms (FKSI-DRS): a tool used to measure the severity of symptoms specifically related to kidney cancer in patients

European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaires: an assessment that measures quality of life in patients with cancer

Intent-to-treat population: all patients who were initially randomly assigned to different treatment groups, regardless of whether they actually received the assigned treatment or completed the study

ECOG performance status of 0 or 1: a scoring system on a patient’s ability to complete activities of daily living. A score of 0 or 1 indicates a patient who is fully active or someone who is restricted in physically strenuous activity but ambulatory and able to carry out light work, respectively

Progression-free survival: the time during and after treatment when a patient with cancer lives without their disease worsening

Overall survival: the length of time from diagnosis or treatment initiation when a patient with cancer is still alive

Objective response rate: the percentage of patients whose cancer shrinks or disappears after treatment

Proteinuria: a higher than normal level of protein in urine, which may be an indicator of kidney damage

Data on PROs, which were presented at the 2025 Genitourinary Cancers Symposium, demonstrated that Fotivda maintained the mean scores for the Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index-Disease-Related Symptoms (FKSI-DRS) and European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaires.

In the intent-to-treat (ITT) populations from the Fotivda/Opdivo versus Fotivda monotherapy arms, respectively, the mean FKSI-DRS scores at baseline were 28.8 versus 29.3; at week 24, these scores were 29.9 versus 29.4. The mean EORTC QLQ-C30 scores at baseline were 63.4 versus 66.2 in the combination versus monotherapy arms, respectively; at week 24, these mean scores were 68.7 versus 64.8. Patients treated with the combination versus monotherapy in the second line had mean FKSI-DRS scores at baseline of 29.5 versus 29.1; at week 24, these mean scores were 30.1 versus 29.3. Mean EORTC QLQ-C30 scores at baseline in the combination versus monotherapy arms in the second line were 65 versus 67.1; these mean scores at week 24 were 68.7 versus 64.6. In the third-line setting, mean FKSI-DRS scores at baseline were 27.6 versus 29.5; these mean scores at week 24 were 29.5 versus 29.6. Mean EORTC QLQ-C30 scores at baseline in the combination versus monotherapy arms in the third were 60.5 versus 64.9, with mean scores at week 24 of 68.6 versus 65.1.

“In the [Fotivda monotherapy] arm, improvement in FKSI-DRS and EORTC QLQ-C30 scores were numerically greater in patients receiving second-line treatment than third-line treatment, while … fewer patients reported deterioration in the second line than in the third line,” lead study author Dr. Kathryn Beckermann and coauthors wrote in a poster presented at the meeting.

Beckermann is an assistant professor in the Department of Medicine, Division of Hematology and Oncology at Vanderbilt School of Medicine in Nashville, Tennessee.

The TiNivo-2 study compared Fotivda/Opdivo with Fotivda monotherapy in patients with locally advanced or metastatic clear cell RCC following progression on one or two systemic therapies and at least one ICI. The trial enrolled patients who had radiographic progression during or after at least six weeks of treatment with an ICI in the first or second line; recovered from side effects of previous therapies to grade 1 or baseline; had confirmed clear cell RCC; measurable disease; and an ECOG performance status of 0 or 1.

Eligible patients were randomly assigned to receive Fotivda/Opdivo (171 patients) or Fotivda monotherapy (172 patients). Cycles were 28 days, and treatment was continued until progression or unacceptable toxicity. All patients discontinued Opdivo after two years of treatment.

Researchers has several outcomes of interest including progression-free survival (PFS), overall survival objective response rate and duration of response. An exploratory area of interest was quality of life (QOL).

The FKSI-DRS and EORTC QLQ-C30 summary scores showed that there was not a significant change in symptom scores over time in the combination and monotherapy arms. Specifically in the second and third line, patients from both arms also demonstrated a similar trend in FKSI-DRS and EORTC QLQ-C30 summary scores, with maintained symptom scores over time.

Regarding QOL scores, FKSI-DRS and EORTC QLQ-C30 questionnaires reported consistent trends and proportions of patients with improved (increases in scores of at least 3 points at any point during the study), stable (a change in score of 3 or fewer points confirmed at the next consecutive visit), or deteriorated symptoms (decrease in score of at least 3 points at any point during the study). Based on the FKSI-DRS questionnaire, patients from the combination versus monotherapy arms, respectively, had improved (28.2% versus 22.9%), stable (47.2% versus 53.5%), and deteriorated symptoms (24.6% versus 23.6%). The EORTC QLQ-C30 questionnaire among patients in the combination versus monotherapy arms, respectively, revealed improved (27.7% versus 21.3%), stable (48.9% versus 53.7%), and deteriorated symptoms (23.4% versus 25%).

“Approximately 75% of all patients reported improved or stable kidney cancer and cancer-treatment related symptoms in both treatment arms,” the study authors wrote in the poster.

In patients treated with the combination versus monotherapy in the second line, respectively, FKSI-DRS reflected improved (28% versus 27.5%), stable (52.7% versus 53.8%), and deteriorated (19.4% versus 18.7%) health-related QOL (HRQOL) scores. In the third line, patients in the combination versus monotherapy arms, respectively, had improved (28.6% versus 15.1%), stable (36.7% versus 52.8%), and deteriorated (34.7% versus 32.1%) HRQOL scores. Based on EORTC QLQ-C30, patients from the combination versus monotherapy arms, respectively, treated in the second line had improved (27.8% versus 23%), stable (52.2% versus 56.3%), and deteriorated (20% versus 20.7%) HRQOL scores. Patients treated with the combination versus monotherapy in the third line, respectively, showed improved (27.7% versus 18.4%), stable (42.6% versus 49%) and deteriorated (29.8% versus 32.7%) HRQOL scores.

The rate of PFS events that occurred in patients treated in the combination (111 patients) versus monotherapy (105 patients) arms, respectively, in the second line, was 64% versus 61%; median PFS was 7.3 months versus 9.2 months. Among patients treated with the combination (60 patients) versus monotherapy (67 patients) in the third line, PFS events occurred in 78% versus 72%, respectively; median PFS was 4.8 months versus 5.5 months.

The type and frequency of safety events in the Fotivda monotherapy arm were consistent with the known safety profile of Fotivda, confirming its tolerability. 

Treatment-emergent side effects that occurred in 15% or more of patients in the combination versus monotherapy arms, respectively, included hypertension (37% versus 40%), fatigue (29% versus 40%), diarrhea (30% versus 36%), nausea (16% versus 28%), decreased appetite (22% versus 27%), vomiting (12% versus 21%), weakness (23% versus 21%), proteinuria (10% versus 18%), constipation (10% versus 17%), joint pain (16% versus 16%), cough (16% versus 15%), hypothyroidism (9% versus 15%), anemia (17% versus 9%) and itching (16% versus 6%).

“For certain [treatment-emergent side effects], such as fatigue, nausea, vomiting, proteinuria, and hypothyroidism, the combination group showed lower numerical rates,” the study authors wrote. “However, this was not the case for anemia [or] pruritus, which showed the reverse. The lower dose in the combination [group] potentially explains the lower rate of [treatment-emergent side effects] associated with VEGF [tyrosine kinase inhibitors].”

"Patient-reported outcomes (PROs) for tivozanib (TIVO) + nivolumab (NIVO) vs TIVO monotherapy in patients with renal cell carcinoma (RCC) following an immune checkpoint inhibitor (ICI): results of the phase 3 TiNivo-2 study" by Dr. Kathryn Beckermann, et al., 

The combination of Fotivda (tivozanib) and Opdivo (nivolumab) demonstrated comparable patient-reported outcomes (PROs) to Fotivda monotherapy in treating advanced or metastatic clear cell renal cell carcinoma (RCC) post-immune checkpoint inhibitor (ICI) therapy. The phase 3 TiNivo-2 study showed maintained symptom scores over time, with similar trends in quality of life (QOL) scores between treatment arms. Safety profiles were consistent with known data, with some treatment-emergent side effects being less frequent in the combination group, potentially due to lower dosing of VEGF tyrosine kinase inhibitors.

Patient-reported outcomes were similar for Fotivda with or without Opdivo in advanced clear cell RCC.

Outcomes May Be Consistent With Fotivda Alone or With Opdivo in Kidney Cancer Subset

Krazati and Erbitux show efficacy for heavily pretreated patients with advanced colorectal cancer harboring the KRAS G12C mutation.

Among heavily pretreated patients with KRAS G12C-mutant unresectable or metastatic colorectal cancer (mCRC), the combination of Krazati (adagrasib) and Erbitux (cetuximab) has shown clinically meaningful efficacy, as displayed by longer-term follow-up analysis from the phase 1/2 KRYSTAL-1 trial presented at the 2025 Gastrointestinal Cancers Symposium.

At a median follow-up of 20.4 months, updated data showed that the overall response rate (ORR) was 34% per blinded independent central review (BICR) and 43% when assessed by investigator review. Best overall response per BICR and investigator review, respectively, included complete response (0%; 0%), partial response (34%; 43%), stable disease (51%; 44%), progressive disease (6%; 5%) and not evaluable (9%; 9%). The disease control rate (DCR) was 85% per BICR; the DCR was 86% (per investigator review. The median duration of response (DOR) was 5.8 months per BICR; the median DOR was 5.9 per investigator review.

“With longer follow-up, [Krazati] plus [Erbitux] continued to demonstrate clinically meaningful efficacy in heavily pretreated patients with KRAS G12C–mutated CRC,” lead study author Dr. Rona Yaeger said in a poster presentation on the data. “These updated results are consistent with those from the primary analysis and represent the longest follow-up for dual KRAS G12C/EGFR blockade in this setting.”

Complete response: the disappearance of cancer.

Disease control rate: patients whose disease disappeared, shrunk or was stable from treatment.

ECOG performance status: a way of measuring patients’ ability to complete daily tasks, with a lower score meaning greater independence.

Overall response rate: patients who responded completely or partially to treatment.

Progression-free survival: the time a patient lives without their disease spreading or worsening.

Yaeger is an associate attending physician and gastrointestinal medical oncologist and early drug development specialist at Memorial Sloan Kettering Cancer Center in New York.

The FDA granted accelerated approval to Krazati/Erbitux in June 2024 for the treatment of adult patients with KRAS G12C–mutated locally advanced or mCRC who were previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

The open-label, nonrandomized, multiple-expansion cohort phase 1/2 trial evaluated the safety and efficacy of Krazati/Erbitux in patients with unresectable or metastatic KRAS G12C–mutated CRC. Eligibility criteria included having no available treatment options with curative intent or refusing or being ineligible for standard of care treatment in phase 1 and 2; receiving previous treatment with fluoropyrimidine, irinotecan, oxaliplatin and a VEGF/VEGFR inhibitor in phase 2; and having a ECOG performance status of 0 or 1.

In the phase 1 portion of the study, patients (32 patients) were treated with 600 milligrams (mg) of Krazati twice daily plus 400 mg/m

 of Erbitux, which was followed by 250 mg/m

 every two weeks administration thereafter. Patients in the phase 2 portion (62 patients) were treated with 600 mg of Krazati twice daily plus 500 mg/m

The median age was 57 years in the overall Krazati/Erbitux cohort (94 patients), and women consisted of 53% of the patient population. Regarding race, 71% were White, 14% were Black or African American and 5% were Asian; 80% identified as not Hispanic or Latino/a, 17% were Hispanic or Latino/a, and ethnicity data were missing in 3%. Patients had an ECOG performance status of 0 (51%) or 1 (49%). Prior lines of therapy included one (9%), two (36%), three (31%) and four or more (24%). Metastatic disease sites per BICR were the lung in 71% of patients and the liver in 64%. Concurrent molecular alterations included the TP53 mutation (74%), PIK3CA mutation (18%), EGFR amplification (2%), and NTRK fusion (1%).

In the subgroup analysis of ORR per BICR among patients from the overall Krazati/Erbitux cohort (94 patients), patients 65 years of age or younger had an ORR of 37% versus those 65 years of age or older who had an ORR of 29%. The ORR in men was 32% versus 36% in women. The ORR at a baseline ECOG performance status of 0 was 44% compared with 24% in those with an ECOG performance status of 1. Those with lung metastases at baseline had an ORR of 35% compared with 32% in those without lung metastases at baseline. Regarding patients with liver metastases at baseline, the ORR was 35% versus 32% in those without. Patients with positive TP53 mutation status had an ORR of 37% versus 24% in those with negative TP53 mutation status. Those with positive PIK3CA mutation status had an ORR of 36% versus 32% in those with negative PIK3CA mutation status. In patients treated with two or fewer prior systemic therapies, the ORR was 24% versus 42% in those treated with two or more prior systemic therapies.

The median progression-free survival (PFS) was 6.9 months and 6.9 months per BICR and investigator review, respectively. The 6- and 12-month PFS rates were 57% and 19%, respectively, per BICR vs the 6- and 12-month PFS rates of 61% and 19%, respectively, per investigator review. The median OS was 16 months, with 6- and 12-month OS rates of 88% and 66%, respectively.

No new safety signals were identified with longer follow-up. The most common treatment-related side effects included nausea (any grade, 61%; grade 3 (severe)/4(life-threatening), 2%), vomiting (any grade, 51%; grade 3/4, 0%), diarrhea (any grade, 49%; grade 3/4, 1%), dermatitis acneiform (any grade, 48%; grade 3/4, 2%), fatigue (any grade, 44%; grade 3/4, 1%), dry skin (any grade, 35%; grade 3/4, 0%), hypomagnesemia (any grade, 29%; grade 3/4, 3%), headache (any grade, 27%; grade 3/4, 3%), and rash (any grade, 22%; grade 3/4, 2%). Grade 3/4 treatment-related side effects occurred in 28% of patients and no grade 5 (fatal) treatment-related side effects were reported. Of note, treatment-related side effects led to dose reductions of Krazati in 31% of patients and Erbitux in 6%. Dose interruptions of Krazati and Erbitux because of treatment-related aide effectw were required by 37% and 35% of patients, respectively. Treatment-related side effects leading to treatment discontinuations were reported in 1% of patients with Krazati and 9% with Erbitux.

“These longer follow-up results further support the FDA approval of [Krazati]/[Erbitux] as a standard of care in patients with previously treated KRAS G12C–mutated advanced mCRC,” Yaeger concluded in the poster presentation. “The efficacy of second-line [Krazati] plus Erbitux versus chemotherapy in this patient population is currently being investigated in the phase 3 KRYSTAL-10 study.”

 G12C–mutated metastatic colorectal cancer: longer follow-up analysis from KRYSTAL-1” by Dr. Rona Yaeger et al., 

The combination of Krazati (adagrasib) and Erbitux (cetuximab) demonstrates significant efficacy in heavily pretreated patients with KRAS G12C-mutant unresectable or metastatic colorectal cancer, as shown in the KRYSTAL-1 trial. With a median follow-up of 20.4 months, the overall response rate was 34% per blinded independent central review and 43% per investigator review. The disease control rate was 85% and 86%, respectively. The median progression-free survival was 6.9 months, and the median overall survival was 16 months. No new safety concerns emerged, supporting the FDA's approval of this treatment.

Findings presented at the Gastrointestinal Cancers Symposium showed the efficacy of Krazati and Erbitux for some patients with unresectable or metastatic colorectal cancer.

Caroline Seymour

TAR-200 Shows High Response Rates in Bladder Cancer Subset

Bavencio and BSC Extends Survival in Bladder Cancer, Regardless of Diabetes Status

Outcomes May Be Consistent With Fotivda Alone or With Opdivo in Kidney Cancer Subset

Krazati and Erbitux Effective for KRAS G12C-Mutant Advanced mCRC

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