Courtney Flaherty 

Patients with cisplatin-eligible muscle-invasive bladder cancer (MIBC) who received neoadjuvant (treatment as the first step to shrink a tumor) Imfinzi (durvalumab) plus chemotherapy, followed by adjuvant (additional treatment) Imfinzi, had significant improvements in survival compared with neoadjuvant chemotherapy alone without compromising the completion of surgery.

Findings from the phase 3 NIAGARA study were presented at the 2024 ESMO Congress. Results showed that the median event-free survival (the time a patient remains free from complications or events that the therapy was meant to delay or prevent; EFS) was not reached in the perioperative Imfinzi arm (533 patients) versus 46.1 months in the chemotherapy comparator arm (530 patients). Of note, when EFF is not reached in a trial, this may indicate not enough information for the researchers to assess at the time, or so few patients experienced this outcome to reach a statistically significant conclusion. At a median follow-up of 42.3 months, the 12- and 24-month EFS rates with the Imfinzi regimen were 76% and 67.8%, respectively; respective rates with the placebo regimen were 69.9% and 59.8%.

Patients with muscle-invasive bladder cancer who received Imfinzi plus chemotherapy before and after surgery had significantly longer survival compared to those who received chemotherapy alone.

Imfinzi did not delay surgery or impact the ability of patients to undergo or complete the procedure.

Patients treated with Imfinzi had a significantly longer time before the cancer returned or progressed compared to those receiving chemotherapy alone.

Imfinzi reduced the risk of death by 25% compared to the placebo.

A subsequent EFS sensitivity analysis excluding patients who did not undergo radical cystectomy (surgery to remove the entire bladder) showed that the median EFS was not reached in the perioperative Imfinzi arm versus not reached in the comparator arm. The 12- and 24-month EFS rates were 82.3% and 73.5%, respectively, with the Imfinzi regimen; respective rates were 79.4% and 67.9% with the placebo regimen.

Moreover, the perioperative Imfinzi regimen reduced the risk of death by 25% compared with the placebo regimen in the intention-to-treat (patients randomized to a treatment regardless of whether they actually received the treatment; ITT) population. At a median follow-up of 46.3 months, patients in the perioperative Imfinzi arm achieved 12- and 24-month overall survival (the time when a patient with cancer is still alive; OS) rates of 89.5% and 82.2%, respectively. Corresponding rates in the comparator arm were 86.5% and 75.2%. Notably, 53 and 93 patients in the Imfinzi and comparator arms, respectively, had received at least one subsequent anticancer therapy following treatment discontinuation at the time of this analysis.

Both the EFS and OS benefits with the Imfinzi regimen were reported across all subgroups.

At a data cutoff of January 2022, the planned formal analysis of pathologic complete response (when all visible evidence of cancer is eliminated after treatment; pCR) rate did not show significant benefit with the Imfinzi (33.8%) versus placebo regimen (25.8%), as the data did not meet the threshold for significance. However, 59 evaluable samples from the ITT population were incorrectly attributed as non-responders.

A re-analysis of pCR including these omitted samples was accordingly conducted. At a data cutoff of April 2024, nominal statistical significance was reported in favor of the Imfinzi arm. The pCR rates were 37.3% in the Imfinzi arm and 27.5% in the comparator arm.

“NIAGARA is the first global phase 3 study to evaluate a perioperative immune checkpoint inhibitor, [Imfinzi] combined with neoadjuvant chemotherapy in cisplatin-eligible patients with MIBC,” lead study author Dr. Thomas Powles, noted during an oral presentation of the data. “The pCR results and significant OS benefit [observed in this analysis] support the perioperative approach, and neoadjuvant [Imfinzi] did not delay surgery [nor] impact the ability of patients to undergo or complete surgery.”

Powles is a professor of Genitourinary Oncology, lead for Solid Tumor Research, and director of Barts Cancer Centre at St. Bartholomew’s Hospital in London.

The NIAGARA trial enrolled adults with cisplatin-eligible MIBC who were evaluated and confirmed for radical cystectomy and had urothelial carcinoma (cancer that develops in the urinary tract). Patients were also required to have an ECOG performance status (PS) of 0 or 1 (fully active or some restrictions on strenuous activity, and a creatinine clearance (CrCl) of at least 40 mL/min (indicating normal kidney function).

Of the 1,530 patients enrolled onto the study, 1,063 patients were randomly assigned to receive Imfinzi plus gemcitabine/cisplatin, followed by Imfinzi alone after radical cystectomy; or gemcitabine/cisplatin alone prior to cystectomy, followed by no further treatment after surgery.

The main areas of focus in the trial were EFS and pCR rate at the time of cystectomy. Other areas of interest included OS and safety.

A total of 530 and 526 patients assigned to the Imfinzi and comparator arms, respectively, started neoadjuvant treatment; 113 and 137 discontinued treatment prior to surgery. The median time from the last dose of neoadjuvant therapy to cystectomy was 39 days and 38 days in these respective arms.

Cystectomy was completed in 470 patients in the Imfinzi arm and 446 patients in the placebo arm; 63 and 84 patients, respectively, elected not to undergo surgery. Of the 383 patients who started adjuvant treatment in the Imfinzi arm, 95 discontinued treatment. At the time of follow-up, 379 patients in the Imfinzi arm and 333 patients in the placebo arm were ongoing in the study. No patients were still on study treatment at the data cutoff.

Powles noted that, “The addition of perioperative [Imfinzi] to neoadjuvant chemotherapy was tolerable and manageable, with no new safety signals [observed].”

The majority of patients in both arms experienced side effects of any cause (99% in the Imfinzi arm; 100% in the comparator arm). Of these, 69% and 68%, respectively, were grade 3/4 (severe or life threatening); serious side effects were reported in 62% and 55% of patients, respectively. Side effects leading to death (5%; 6%), discontinuation of study treatment (21%; 15%), discontinuation of neoadjuvant Imfinzi (9%; not applicable); discontinuation of neoadjuvant chemotherapy (14%; 15%), not undergoing radical cystectomy (1%; 1%), a delay in surgery (2%; 1%) and discontinuation of adjuvant Imfinzi (8%; not applicable) were reported. Forty-one percent of patients in both arms experienced potential treatment-related side effects, 0.6% of which resulted in death in both arms. Any-grade immune-mediated side effects were reported in 21% of patients in the Imfinzi arm versus 3% of patients in the comparator arm.

Specifically within the adjuvant phase, side effects of any cause were observed in 86% and 71% of patients who received perioperative Imfinzi versus the placebo regimen. Grade 3/4 side effects were reported in 31% and 24% of patients, respectively. Serious side effects occurred in 26% and 22% of patients, and side effects led to death in 2% of patients across both groups. Potential treatment-related side effects were seen in 41% and 6% of patients in the Imfinzi and placebo arms, respectively; 6% and 1% of these were grade 3/4. No potential adjuvant treatment-related side effects led to death in either arm.

The most common any-grade side effects were nausea (Imfinzi arm, 54%; placebo arm, 49%), anemia (39%; 41%), constipation (39%; 39%), fatigue (36%; 32%), urinary tract infection (30%; 29%), decreased appetite (27%; 25%), neutropenia (low number of neutrophils, a type of white blood cell, that helps the body defend itself against infections; 26%; 31%), fever (21%; 17%), diarrhea (21%; 14%), vomiting (19%; 18%), blood creatinine increase (potentially indicating kidney damage; 19%; 15%), weakness (18%; 18%), neutrophil count decrease (decrease in the number of neutrophils, a type of white blood cell, in the blood that helps against infections; 15%; 14%) and itching (15%; 7%).

“[Overall,] NIAGARA supports perioperative [Imfinzi] with neoadjuvant chemotherapy as a potential new standard treatment for patients with cisplatin-eligible MIBC,” Powles concluded.

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Articles

Imfinzi and chemotherapy before surgery, followed by Imfinzi after surgery, generated survival benefits in cisplatin-eligible muscle-invasive bladder cancer. 

Perioperative Imfinzi, Neoadjuvant Chemo Improves Survival in Muscle-Invasive Bladder Cancer

Patients with early-stage triple-negative breast cancer demonstrated improved survival outcomes after treatment with perioperative (time around surgery) Keytruda (pembrolizumab) with chemotherapy, followed by Keytruda after surgery, according to a presentation at the 

Findings from the phase 3 KEYNOTE-522 study were presented, which showed that the perioperative Keytruda-chemotherapy combination reduced the risk of death by 34%, compared with patients who received placebo (inactive drug) plus chemotherapy.

Patients with early-stage triple-negative breast cancer treated with Keytruda and chemotherapy demonstrated a 34% reduced risk of death compared to those receiving placebo and chemotherapy.

The positive effects of the Keytruda regimen persisted over time, with patients experiencing significant improvements in overall survival, event-free survival and pathological complete response rates.

While the overall population benefited from the Keytruda regimen, patients with PD-L1-positive tumors showed particular improvements in outcomes.

Patients who achieved a pathological complete response, regardless of treatment group, experienced excellent long-term survival.

“Most importantly, [data from the study] demonstrated that [the Keytruda regimen] reduced the risk of death by 34%,” lead study author Dr. Peter Schmid, of Barts Cancer Institute at Queen Mary University in London, said in a press briefing at the ESMO Congress.

The Effect of Keytruda-Chemotherapy Versus Placebo-Chemotherapy Combinations

In the study, patients were randomly assigned to receive either Keytruda plus chemotherapy or placebo plus chemotherapy as first-line treatment perioperatively. After, patients in the respective treatment groups received Keytruda or placebo plus more chemotherapy after undergoing surgery.

The trial’s dual primary end points (main results measured at the end of the study) were pathological complete response (pCR; no more signs of cancer after treatment) rate and event-free survival (EFS; time after treatment when patients remain free from complications or events caused by cancer) in the intention-to-treat population.

Secondary end points included pCR and EFS in patients with PD-L1-positive tumors, and overall survival (OS; time patients live, regardless of disease status) among all patients and those with PD-L1-positive tumors.

At a median follow-up of 75.1 months, 784 patients treated in the Keytruda-chemotherapy group achieved a five-year OS rate of 86.6% versus 81.7% for 360 patients in the placebo group. The OS event rates were 14.7% and 21.8% for the Keytruda-chemotherapy and placebo groups, respectively.

, from the first interim analysis of KEYNOTE-522 showed that patients in the Keytruda group achieved a pCR rate of 64.8% compared with 51.2% in patients from the placebo group, at a median follow-up of 15.5 months.

Additionally, prior data from the fourth interim analysis, also published in 

, demonstrated that the Keytruda regimen led to a significant improvement in EFS versus the placebo regimen. The 36-month EFS rate was 84.5% in the Keytruda group versus 76.8% in the placebo group.

 as a neoadjuvant (presurgical) treatment, then continued as Keytruda only as a treatment after surgery, for the treatment of patients with high-risk, early-stage triple-negative breast cancer based on prior data from KEYNOTE-522.

Updated efficacy analysis showed that the Keytruda regimen maintained a significant improvement in EFS versus the placebo regimen in the overall population. The five-year EFS rates were 81.2% for the Keytruda group versus 72.2% for the placebo group. EFS events were reported in 20.3% of patients in the experimental group versus 29.2% of patients in the control group.

Patients who achieved a pCR in the study also experienced an OS benefit, regardless of the treatment group. For responders, the five-year OS rate was 95.1% in 495 patients from the Keytruda group versus 94.4% in 217 patients from the placebo group. In non-responders, the five-year OS rate was 71.8% in 289 patients from the Keytruda group versus 65.7% in 173 patients from the placebo group.

Eligible patients enrolled in the trial must have been at least 18 years old, with triple-negative breast cancer in all foci (can only view tumor cells microscopically). Patients needed to have newly diagnosed, previously untreated, nonmetastatic disease, defined as tumor stage T1c, nodal stage N1-2, or tumor stage T2-4, nodal stage N0-2. Eligible patients had an ECOG performance status of 0 or 1 (meaning patients can perform daily tasks independently or with some restrictions) and adequate organ function. Notably, those with bilateral or multifocal primary tumors and inflammatory breast cancers were allowed to participate, according to the presentation.

Patients with early triple-negative breast cancer had improved survival outcomes after receiving presurgical Keytruda plus chemotherapy and postsurgical Keytruda. 

Presurgical Keytruda-Chemo Combo With Postsurgical Keytruda May Improve Survival in Early TNBC

TORL-1-23, a CLDN6–targeted antibody-drug conjugate (ADC), generated responses and was well tolerated in heavily pretreated, CLDN6-positive advanced solid tumors, including platinum-resistant ovarian cancer, according to data from the phase 1 TORL-123-001 trial, presented at the 

According to the National Cancer Institute, an ADC is a substance consisting of a monoclonal antibody that binds to specific proteins or receptors within cancer cells, which enter the cell to kill it without harming other cells.

TORL-1-23 demonstrated promising efficacy in heavily pretreated patients with CLDN6-positive advanced solid tumors, including platinum-resistant ovarian cancer.

The antibody-drug conjugate was well tolerated with a favorable safety profile, and the maximum-tolerated dose had not yet been reached.

Responses observed with TORL-1-23 were durable, suggesting the potential for long-lasting benefits.

TORL-1-23's targeting of CLDN6, a protein overexpressed in various cancers, represents a targeted approach to cancer treatment.

Findings showed that among all efficacy-evaluable patients, 19 patients treated with TORL-1-23 at doses of less than 2.4 milligrams (mg) per kilogram (kg), the overall response rate (ORR; the percentage of patients with a positive response to treatment) was 26%, which exclusively comprised partial responses (PRs; a decrease in tumor size or the extent of cancer in the body); 42% of patients had stable disease (SD; cancer that is neither increasing nor decreasing in severity or extent) and 32% of patients had progressive disease (PD; cancer that spreads, grows or worsens). At a dose of 2.4 mg/kg (19 patients), the ORR was 42% with all responders achieving a PR; the rates of SD and PD were 47% and 11%, respectively. At a dose of 3 mg/kg (26 patients), the ORR was 31%, including a complete response (the disappearance of all signs of cancer from treatment) rate of 4% and a PR rate of 27%; the respective SD and PD rates were 46% and 23%.

In patients with CLDN6-positive platinum-resistant ovarian cancer, the ORRs were 30% at doses less than 2.4 mg/kg, 50% (4 out of 8 patients) at the 2.4 mg/kg dose, and 42% (5 out of 12 patients) at the 3 mg/kg dose.

Lead study author Dr. Gottfried E. Konecny said the ADC was well tolerated with a favorable safety profile. The risk of neutropenia (lower than normal levels of neutrophils, a type of white blood cell) was mitigated by prophylactic pegfilgrastim (a medication used to prevent neutropenia), and the maximum-tolerated dose (MTD) of TORL-1-23 had not yet been reached.

“The promising activity was confirmed as being durable and deep. … [There were encouraging data for] all patients treated in dose escalation, particularly in [patients with] ovarian cancer treated at 2.4 mg/kg and 3 mg/kg,” Konecny said during a presentation of the data. He is the lead clinician for gynecologic oncology in the Department of Medicine at the University of California, Los Angeles.

CLDN6 is expressed at high levels in a variety of cancers and has little to no expression in normal tissues, Konecny explained during the presentation.

The phase 1, first-in-human study enrolled patients at least 18 years of age with advanced solid tumors who had measurable disease, an ECOG performance status of 0 or 1 (fully active or limited strenuous activity) and adequate organ function.

TORL-1-23 is being evaluated at 11 different dose levels ranging from 0.2 mg/kg to 3.6 mg/kg. At dose level 9 (3 mg/kg), dose level 10 (4.0 mg/kg), and dose level 11 (3.6 mg/kg), prophylactic pegfilgrastim is also being administered at a dose of at least 3 mg/kg.

The dose-expansion portion of the study includes patients with CLDN6-positive platinum-resistant ovarian cancer, CLDN6-positive refractory non-small cell lung cancer (NSCLC), other CLDN6-positive refractory cancers, and CLDN6-low refractory cancers. Within each of those groups, approximately 10 to 20 patients are being treated at both 2.4 mg/kg and 3 mg/kg.

The primary objectives of the study are safety, tolerability, dose-limiting toxicities and determining the MTD and recommended phase 2 dose.

Among patients enrolled in the dose-escalation portion of the study (51 patients), the median age was 61 years. Tumor types included ovarian (36 patients), testicular (4 patients), endometrial (7 patients), NSCLC (2 patients) and other (2 patients). This patient population received a median of four prior lines of therapy. Thirty-eight patients had CLDN6-positive disease per immunohistochemistry (IHC).

In dose expansion (30 patients), the median age was 65 years. Tumor types included ovarian (14 patients), testicular (1 patient), endometrial (6 patients), NSCLC (6 patients) and other (3 patients). Patients received a median of three prior lines of therapy. Twenty-seven patients had CLDN6-positive disease per IHC.

In patients with platinum-resistant ovarian cancer, the median duration of response was approximately 22 weeks for those treated with the 2.4-mg/kg dose and approximately 30 weeks for those treated at the 3-mg/kg dose in combination with prophylactic pegfilgrastim.

Safety data from dose expansion showed that at the 2.4-mg/kg dose (16 patients), the most common side effects included anemia (any severity, 25%; severe or worse, 0%), neutropenia (31%; 19%), nausea (67%; 0%), constipation (6%; 0%), diarrhea (25%; 6%), vomiting (25%; 0%), fatigue (56%; 19%), arthralgia (joint pain or soreness; 31%; 0%), myalgia (muscle pain; 19%; 6%), neuropathy (nerve damage; 25%; 0%) and alopecia (hair loss; 56%; 0%).

At the 3.0-mg/kg dose (14 patients), the most frequent side effects consisted of anemia (any severity, 29%; grade ≥3, 0%), neutropenia (7%; 7%), nausea (64%; 0%), constipation (29%; 0%), diarrhea (21%; 0%), vomiting (21%; 0%), fatigue (79%; 14%), arthralgia (43%; 0%), myalgia (21%; 0%), neuropathy (57%; 0%) and alopecia (69%; 0%).

“There is a registrational phase 2 study being initiated globally in CLDN6-positive platinum-resistant [ovarian cancer], and the molecule is under further evaluation in other CLDN6-positive cancers, including NSCLC,” Konecny concluded.

Treatment with the antibody-drug conjugate TORL-1-23 was safe and tolerable in heavily pretreated, CLDN6-positive advanced solid tumors, including platinum-resistant ovarian cancer.

Antibody-Drug Conjugate Is Tolerable, Active in CLDN6-Positive Solid Tumors Including Ovarian Cancer

The novel drug, olomorasib, when given with Keytruda (pembrolizumab), was safe and effective in treating KRAS G12C-mutant non-small cell lung cancer (NSCLC), according to data from the phase 1/2 LOXO-RAS-20001 trial presented at the 2024 ASCO Breakthrough Conference.

A new drug, olomorasib, was tested in combination with Keytruda for treating KRAS G12C-mutant non-small cell lung cancer (NSCLC).

The combination showed promising results in both patients with first-line treatment and those who had received previous treatments.

The most common response to treatment was a partial response, meaning the tumor shrank but did not disappear completely.

The most frequent side effects were not mentioned in the provided text.

In efficacy-evaluable patients with metastatic disease being treated in the first line (17 patients), the objective response rate (ORR; percentage of patients whose disease shrinks or disappears from treatment) with the combination was 77% and was composed entirely of partial responses (PR; disease shrunk but did not disappear). The best responses to treatment included stable disease (SD; 12%) and progressive disease (PD; 6%), although 6% of patients were not evaluable (NE). At a median follow-up of 5.5 months, the median progression-free survival (PFS; time patients live without their disease worsening) was NE. The estimated six- and 12-month PFS rates were both 72.8%.

 G12C-mutant NSCLC (43 patients), the ORR was 40% and included all PRs. PD and SD were the best responses in 42% and 16% of patients, respectively. The best response was NE in 2% of patients. Notably, 81% of previously treated patients had received prior immunotherapy.

Across both groups, the median time on treatment was 3.5 months (range, 0 to 17 months), the median time to response was 1.4 months and the median duration of response was NE.

“Olomorasib in combination with pembrolizumab demonstrates promising antitumor activity,” lead study author Dr. Yutaka Fujiwara, chief of the Department of Thoracic Oncology at Aichi Cancer Center Hospital in Aichi, Japan, stated in an oral presentation of the data. “We have responses at both the 50-milligram and 100-milligram dose level regardless of PD-L1 score and previous treatment, including immunotherapy and KRAS G12C inhibitor.”

PD-L1 is a protein that immunotherapy agents, like Keytruda, target. Higher PD-L1 scores are typically associated with a better response to these agents, according to the American Cancer Society.

Immunotherapy remains the cornerstone of first-line treatment for patients with 

 G12C-mutant NSCLC; however, outcomes for these patients remain suboptimal.

 G12C-mutant NSCLC remains poor, despite the approval of first-generation KRAS inhibitors, which are currently limited to second or later line use. Further progress may be achieved with the addition of targeted therapy to immunotherapy in NSCLC,” Fujiwara added.

Olomorasib, a potent and selective second-generation inhibitor of GDP-bound KRAS G12C, is emerging as a candidate to address these unmet needs. Previously reported data from the LOXO-RAS-20001 study showed that olomorasib, when given alone, demonstrated a favorable safety profile, with treatment-related side effects being predominantly grade 1 (mild). Notably, this safety profile was consistent even in patients who had discontinued previous KRAS G12C inhibitors due to toxicity, indicating a manageable toxicity profile.

Moreover, efficacy for olomorasib monotherapy was consistent across a range of 

G12C-mutant solid tumors. Among patients with NSCLC who were previously treated with a KRAS G12C inhibitor (39 patients), the agent produced an ORR of 41%, with 63% having received a KRAS G12C inhibitor as their immediate prior therapy. The median PFS was 8.1 months.

Notably, preliminary central nervous activity (CNS) activity was seen, with CNS responses observed in patients with NSCLC and measurable brain metastases.

LOXO-RAS-20001 is an open-label, multicenter, study evaluating the safety, tolerability and preliminary efficacy of olomorasib in patients with advanced solid tumors harboring 

The study begins with a phase 1a dose escalation phase evaluating olomorasib monotherapy in 

 G12C-mutant solid tumors, as well as a phase 1b dose expansion and optimization phase assessing olomorasib as both monotherapy and in combination with other agents. The dose expansion phase is further divided into the following five parts: 

NSCLC with prior KRAS G12C inhibitor exposure (part E)

Patients at least 18 years of age with locally advanced or metastatic solid tumors harboring a 

 G12C mutation were enrolled in the study. Other eligibility criteria included measurable disease, an ECOG performance status of 0 or 1 (meaning that they could independently perform all daily tasks), and no prior exposure to a KRAS G12C inhibitor except where indicated. In part B4, patients were permitted to have prior exposure to chemotherapy, anti-PD-L1 therapy, or a KRAS G12C inhibitor. No prior therapy for metastatic disease was permitted in part G.

The study’s main goals were to establish safety and tolerability, as well as the maximum tolerated dose and recommended phase 2 dose of the agent. Key secondary end points included pharmacokinetics (how the body and drug interact); and ORR and duration of response.

The current analysis features patients with 

 G12C-mutant NSCLC who were enrolled in part B4 (48 patients) and part G (16 patients) of the study and received Keytruda plus olomorasib. The data cutoff was March 18, 2024. Patients in this population were treated with Keytruda plus oral olomorasib at a twice-daily dose of 50 milligrams (15 patients) or 100 milligrams (49 patients).

The median age was 67 years of age (range, 42 to 83 years old), and the majority of patients were male (53%), White (47%), and had an ECOG PS of 1 (75%; no restrictions on daily tasks). Brain metastases were observed in 38% of patients and 31% had first-line metastatic disease.

Regarding PD-L1 expression score, 28%, 27%, 27% and 19% had a score of 50% or greater, less than 1%, between 1% to 49%, and unknown, respectively.

“When we look at the PD-L1 scores, there was a well-balanced distribution,” Fujiwara added.

The median number of prior systemic lines of therapy was two (range, 0 to eight prior lines of therapy), and 69% of patients received either platinum-based chemotherapy plus a PD-L1 inhibitor (82%); platinum-based chemotherapy alone (18%); or a KRAS G12C inhibitor (39%). Among patients who were previously exposed to a KRAS G12C inhibitor, patients discontinued treatment due to disease progression (76%), toxicity (18%), and other reasons (6%).

Regarding safety, any grade side effects were observed in 70% of patients across all dose levels and populations; 86% experienced any grade treatment-emergent side effects. Side effects led to dose holds in 25% of patients and olomorasib dose reductions in 17% of patients in the overall population. Only 3% and 11% of patients permanently discontinued olomorasib versus Keytruda, respectively, due to side effects; 5% discontinued both drugs due to side effects.

Common side effects in 10% or more of patients included diarrhea (any grade, 23%; grade 3, 13%), fatigue (16%, 0%), alanine transaminase (ALT) increase (20%; 6%), pruritis (19%; 3%), aspartate transaminase (AST) increase (16%; 8%) and nausea (14%; 0%).

The incidence of side effects in at least 10% of patients included diarrhea (any grade, 28%; grade 3 or higher, 13%), fatigue (27%; 0%), ALT increase (25%; 8%), pruritis (25%; 3%), nausea (23%; 0%), joint pain/stiffness (19%; 0%), AST increase (17%; 8%), vomiting (17%; 0%), anemia (16%; 2%), decreased appetite (14%; 2%), cough (13%; 0%), difficulty breathing (11%; 5%), hypokalemia (11%; 3%) and headache (11%; 0%).

Investigators noted that grade 2 or higher diarrhea was unusually brief, with a median duration of nine days. These events resolved to grade 1 or baseline with dose modification and antidiarrheals in 92% of patients. All grade 3 ALT/AST (indicating liver issues) resolved to grade 1 or baseline after a median of six days following dose modification and/or corticosteroids. No grade 2 or higher ALT/AST elevation had high-risk features.

“Given these promising results, we are currently conducting a global, registrational, phase 3 trial called SUNRAY-01”, Fujiwara concluded. The study will compare first-line olomorasib plus Keytruda with Keytruda plus placebo in 

G12C-mutant, locally advanced or metastatic NSCLC with a PD-L1 expression of at least 50%; or first-line olomorasib versus placebo in combination with Keytruda, pemetrexed and platinum-based chemotherapy in patients with this tumor type regardless of PD-L1 expression. The trial is currently open to enrollment.

Olomorasib plus Keytruda was proven to be safe and well tolerated for patients with KRAS G12C-mutant non-small cell lung cancer.

Courtney Flaherty

Perioperative Imfinzi, Neoadjuvant Chemo Improves Survival in Muscle-Invasive Bladder Cancer

Presurgical Keytruda-Chemo Combo With Postsurgical Keytruda May Improve Survival in Early TNBC

Antibody-Drug Conjugate Is Tolerable, Active in CLDN6-Positive Solid Tumors Including Ovarian Cancer

Olomorasib, Keytruda Combo Is Safe for Lung Cancer Subset

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