Hayley Virgil

Data from patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) treated with axicabtagene ciloleucel (axi-cel; Yescarta) showed that post-CAR T outcomes may not correlate with responsiveness observed with treatment received immediately prior, according to a presentation given during the 2021 Transplantation & Cellular Therapy Meetings.

At a median follow-up of 5.9 months (range, 0.9-31.1), the overall response rate (ORR) achieved by patients who received the CAR T-cell therapy was 63.3%, with 30% of patients experiencing a complete response (CR). As of the last follow-up, approximately half, or 55%, of all patients maintained a response to treatment, while 31.7% (n = 19) had died. Specifically, 84.2% (n = 16) died due to progressive disease.

At 1 month, response to axi-cel was strongly linked with better overall survival (OS; HR, 11.82; 95% CI, 3.72-37.54; 

<.0001) and progression-free survival (PFS; hazard ratio [HR], 6.44; 95% CI, 2.46-16.87; 

<.0001). Patient responsiveness to last therapy received before the CAR T-cell therapy was not found to be significantly associated with changes in either OS (

Moreover, investigators did not observe differences in OS (

 = .64) after designating patients into 2 subgroups based on response: those who did respond versus those who did not. Little difference was observed with regard to ORR between responders and non-responders, at 77.3% and 64.7%, respectively. The number of previous lines of therapy, primary refractory disease, histology,

 status, pre-CAR T bridging therapy, and site of residual disease were not found to be linked with changes in survival.

Although axi-cel has demonstrated efficacy in patients with relapsed/refractory DLBCL, the association of sensitivity to pre-CAR T chemoimmunotherapy with response to the product is not currently known. To this end, investigators launched the single-institution study to compare the outcomes of patients who had chemotherapy-sensitive disease prior to CAR T-cell therapy with those with unresponsive and refractory disease.

The study included patients with DLBCL who consecutively received axi-cel. Positron emission tomography (PET) and computer tomography scans were done prior to treatment with axi-cel, 28 days after infusion, and at the time of the last follow-up. Responses were defined per the Lugano criteria. Both OS and PFS were estimated by using the Kaplan-Meier method, and hazard ratios were estimated using Cox proportional hazard models.

In total, 60 patients with relapsed/refractory disease underwent apheresis for axi-cel, 75.0% (n = 45) of whom had primary DLBCL. The remaining patients had either transformed follicular lymphoma (20.0%; n = 12), primary mediastinal large B-cell lymphoma (3.3%; n = 2), or high-grade B-cell lymphoma (1.7%; n = 1).

The median age of the participants was 62 years, with 36.7% (n = 22) of patients over the age of 65 years, and the majority of population where male (66.7%; n = 40). Additionally, 31.7% (n = 19) of patients received more than 3 prior lines of therapy, and 70.0% (n = 42) received treatment for primary refractory disease. More than half (56.7%; n = 34) of all patients received a bridging therapy prior to undergoing CAR T-cell infusion and 26.7% (n = 16) of patients had previously received a stem cell transplant. Moreover, 35% of patients had received a novel drug prior to CAR T-cell infusion, and 36.7% of patients responded to their last therapy prior to axi-cel.

When evaluating response to the CAR T-cell therapy at PET-1, 30.0% (n = 18) of patients experienced a CR, 33.3% (n = 20) achieved a PR, and 15.0% (n = 9) had disease stability. Fifteen percent (n = 9) of patients experienced progressive disease.

At a median follow-up of 4.78 months (95% CI, 0.96-31.1), the time of the last follow-up, 35.0% of patients (n = 21) had a CR and 20.0% had a partial response (PR; n = 12). Additionally, 3.3% of patients (n = 2) achieved stable disease, while 8.3% (n = 5) experienced progressive disease. At this time, 33.3% (n = 20) of patients were deceased.

Investigators reported an incidence rate of 10% for grade 3/4 cytokine release syndrome (CRS) and 16.7% for grade 3/4 immune effector cell-associated neurotoxicity syndrome. In total, 76.7% of patients (n = 46) experienced CRS with axi-cel, 51.7% (n = 31) experienced central nervous system toxicity, and 48.3% (n = 29) experienced both.

Based on these findings, investigators concluded that these data support the use of CAR T-cell therapy in patients with refractory and unresponsive lymphoma, provided that they are otherwise eligible for treatment.

Iovino L, Wu V, Voutsinas J, et al. Non-responsiveness to immediate pre CAR-T treatment does not preclude response to axicabtagene ciloleucel in relapsed and refractory aggressive B cell lymphomas. Poster presented at: 2021 Transplantation & Cellular Therapy Meetings; February 8-12, 2021; Virtual. Poster 416.

Articles

Data from patients with relapsed/refractory diffuse large B-cell lymphoma treated with axicabtagene ciloleucel showed that post-chimeric antigen receptor T outcomes may not correlate with responsiveness observed with treatment received immediately prior.

Axi-Cel Shows Activity in Relapsed/Refractory DLBCL Regardless of Chemo Sensitivity

In patients with non-muscle invasive bladder cancer (NMIBC) carcinoma in-situ (CIS) who were unresponsive to Bacillus Calmette-Guerin (BCG Vaccine), the addition of N-803 (also known as ALT-803) induced a high rate of complete responses (CRs), findings from a cohort of the phase 2/3 QUILT-3.032 study (NCT03022825) showed.

The findings, presented during the 2021 Genitourinary Cancers Symposium, showed that at a median follow-up of 10.7 months, 71% of evaluable patients (n = 51/72) achieved a CR at any time (95% CI, 59%-81%), meeting the primary end point of the study.

Moreover, investigators reported a 56% probability of maintaining a CR with this approach at 12 months (95% CI, 38.8%-70.3%). Among responders, the estimated median duration of CR was 19.2 months (95% CI, 7.3–not reached [NR]). Notably, the majority of patients, or 87.5%, (n = 70/80) have not progressed to radical cystectomy.

“N-803 is an IL-15 superagonist antibody cytokine fusion protein with significant binding capacity to the IL-2R beta and gamma and increased half-life of the Fc receptor,” Karim Chamie, MD, MSHS, an associate professor in residence of urology and Society of Urologic Oncology Fellowship Director at the University of California, Los Angeles, explained during a presentation on the findings. “This results in significant accrual of T cells and natural killer cells without upregulation of regulatory T cells.”

Results from the phase 1 trial examining N-803 plus BCG indicated that all patients (n = 9) wirh high-risk NMIBC experienced a durable CR or no recurrence. All patients were disease free at 24 months. Based on these data, the FDA granted N-803 a fast track therapy designation in December 2019; this led to the launch of the phase 2/3 trial to further examine this approach.

To be eligible for enrollment on the trial, patients had to have histologically-confirmed BCG-unresponsive CIS with or without Ta or T1. Investigators defined BCG-unresponsive disease as persistent or recurrent CIS within 12 months of being treated with BCG; at least 5 of 6 doses of initial induction course with at least 2 of 3 doses of maintenance treatment or at least 2 of 6 doses of a second induction course were required.

Eighty patients were enrolled to cohort A and they received 50 mg of BCG in combination with 400 μg of N-803 intravesically weekly x6 induction or single re-induction x3 plus maintenance.

The primary end point of the study is CR at any time with a lower bound 95% confidence interval of 20% or greater. At least 24 of the 80 patients enrolled needed to have experienced a CR to meet this end point. Key secondary end points included duration of CR and CR rate at 6 and 12 months. Other end points included progression-free survival, time to cystectomy, cystectomy rate, overall survival, and CR rate at any time per Central Pathology Review.

The mean age of patients enrolled on the study was 72.5 years, with 84% of patients aged 65 years or older. The majority of patients were male (86%), and most patients were white (90%). Eighty-two percent of patients had an ECOG performance status of 0, while 18% had a status of 1.

The median time from last previous BCG dose to study entry was 6.2 months and the mean time was 8.0 months. Additionally, the mean time from last prior BCG dose to first detected recurrence was 3.6 months with a median time of 2.7 months. Moreover, the median time from first detected recurrence to study entry was 2.3 months with a mean time of 4.6 months. The majority of patients had CIS at first recurrence (69%), with 21% had CIS/Ta and 9% had CIS/T1.

“This is a heavily pretreated cohort with the median number of transurethral resection of the bladder tumor being 5.0 [and] a median number of prior BCG instillations being 16.2,” said Chamie. “One hundred percent of patients received prior BCG. In addition to that, 78% of patients received additional therapy with BCG, including checkpoint inhibitors [3%], chemotherapy [59%], interferon [13%], and vicinium [3%].”

N-803 demonstrated promising results compared with other FDA-approved agents or investigational therapeutics in the space, such as pembrolizumab (Keytruda), which yielded a 41% CR rate at any time and a median duration of response of 16.2 months in responders.

 Similarly, nadofaragene firadenovec (rAd-IFNa/Syn3) elicited a 53% CR rate at any time with a median duration of response of 9.7 months.

“N-803 had a smaller cohort, however, the CR rate at any time was much higher, at 71% compared with 41% and 53% for pembrolizumab and nadofaragene, [respectively],” Chamie reported. Our median duration was also favorable, although this must be taken within the context of a shorter median follow-up of 10.7 months. The cystectomy-free rate of 88% also compares favorably, with only 1 of 10 patients demonstrating extravesical disease.”

The most common any-grade treatment-related adverse effects (TRAEs) included dysuria (18%), hematuria (15%), and pollakiuria (14%). Although grade 3 or higher TRAEs were observed during the study, with grade 3 arthralgia, myalgia, and extremity pain each reported in 1% of patients. Serious AEs were also rare but included cardiac disease (1%), hematuria (1%), and adenocarcinoma of the colon (1%).

Notably, no treatment-related serious AEs, no immune-related systemic AEs, and no grade 5 TRAEs were reported. Moreover, no TRAEs led to treatment discontinuation.

“This is an administration profile that is quite familiar to urologists and favorable as an intravesical agent,” concluded Chamie.

Chamie K, Chang S, Gonzalgo M, et al. Phase II/III clinical results of IL-15RαFb superagonist N-803 with BCG in BCG-unresponsive non-invasive bladder cancer (NMIBC) carcinoma in-situ (CIS) patients (cohort A). 

. 2021;39(suppl 6):510. doi:10.1200/JCO.2021.39.6_suppl.510

ImmunityBio granted FDA breakthrough therapy designation for N-803 IL-15 superagonist in non-muscle invasive bladder cancer. News release. BioSpace. December 4, 2019. Accessed February 13, 2021. 

Balar AV, Kamat AM, Kilkarni GS, et al. Pembrolizumab (pembro) for the treatment of patients with Bacillus Calmette-Guérin (BCG) unresponsive, high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): over two years follow-up of KEYNOTE-057. 

. 2020;38(suppl 15):5041-5041. doi:10.1200/JCO.2020.38.15_suppl.5041

Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. 

. 2021;22(1):P107-117. doi:10.1016/S1470-2045(20)30540-4

In patients with non-muscle invasive bladder cancer carcinoma in-situ who were unresponsive to Bacillus Calmette-Guerin, the addition of N-803 induced a high rate of complete responses, findings from a cohort of the phase 2/3 QUILT-3.032 study showed.

High CR Achieved With Addition of N-803 to BCG in BCG-Unresponsive NMIBC CIS

Patient-reported outcomes (PROs) from the phase 3 ADAURA trial (NCT02511106) showed that adjuvant osimertinib (Tagrisso) maintained health-related quality of life (HRQoL) compared with placebo in patients with 

-positive non–small cell lung cancer (NSCLC). No clinically meaningful differences were observed between the 2 study arms, according to findings presented at the International Association for the Study of Lung Cancer's 2020 World Conference on Lung Cancer.

Results indicated a high rate of compliance with regard to the completion of the Short Form-36 (SF-36) health survey, which remained at 85% or higher across all visits in both the osimertinib arm and the placebo arm. Physical component summary scores (PCS) and mental component summary scores (MCS) T-scores were also comparable between the arms (range, 46-47), and were only slightly below the mean values observed in the general population (0.3-0.4 SD below the normative mean).

Patients in both the osimertinib arm and the placebo arm experienced a slight increase from baseline to week 96 in SF-36 PCS, at 1.13 (95% CI, 0.54-1.72) and 2.31 (95% CI, 1.70-2.91), respectively; this was also true with regard to SF-36 MCS, at 1.34 (95% CI, 0.60-2.08) and 2.68 (95% CI, 1.92-3.44), respectively. No clinically meaningful differences were noted between the investigative and control arms of the study (SF-36 PCS, -1.18; 95% CI, -2.02, -0.34; SF-36 MCS, -1.34; 95% CI, ‑2.40, ‑0.28).

While in the disease-free period, more than 80% of patients did not experience a clinically meaningful deterioration in PCS or MCS. For patients who did experience deterioration, no notable differences in time to deterioration (TTD) of PCS (HR, 1.17; 95% CI, 0.82-1.67) or MCS (HR 0.98; 95% CI, 0.70-1.39) were observed in either arm of the study.

"At baseline, we saw that patients had almost the same mean value QoL as the normal population,” lead study author Margarita Tarruella, MD, PhD, a faculty member in the Department of Medical Oncology at the Hospital de la Santa Creu i Sant Pau, said in an interview with 

. “It means that those patients who were going to start osimertinib had the same QoL as the general population. During treatment, what we saw was that this QoL was practically maintained in all of the domains [analyzed]. This treatment, compared with placebo, did not impact patient QoL.”

In December 2020, the FDA approved the third-generation EGFR TKI osimertinib

for the adjuvant treatment of patients with NSCLC whose tumors harbor 

 exon 19 deletions(Ex19del) or exon 21 L858R mutations following surgical resection.

 The approval was based on results from ADAURA, in which osimertinib demonstrated a clinically meaningful and statistically significant disease-free survival (DFS) benefit compared with placebo (HR, 0.20; 99.12% CI, 0.14-0.30; 

The double-blind, phase 3 study enrolled 682 adult patients who had undergone complete surgical resection for stage IB, II, or IIIA 

-mutant NSCLC. To be eligible for enrollment, patients had to be aged 18 years and older or 20 years and older, if they were from Japan and Taiwan. Patients needed to have confirmed primary nonsquamous disease and be positive for exon 19 deletions or exon 21 L858R deletion. A magnetic resonance imaging or computerized tomography scan of the brain were required prior to undergoing randomization or surgery. Additionally, surgical resection needed to be completed with negative margins.

Patients were randomized 1:1 to receive either 80 mg of osimertinib once daily or placebo once daily for 3 years or until recurrence or discontinuation. The primary end point of the study was DFS in those with stage II and IIIA disease, with key secondary end points consisting of DFS in the overall population, landmark analysis of DFS, overall survival, safety, and HRQoL.

In the adjuvant setting, HRQoL is an important clinical consideration for patients who have undergone surgery with curative intent, are free of disease, and are in need of long-term treatment is reduce the risk of recurrence. Regarding adjuvant treatment, the goal is to improve outcomes, while maintaining HRQoL.

For the analysis, patients were asked to complete the SF-36 questionnaire at baseline, 12 weeks, and 24 weeks, followed by every 24 weeks thereafter until treatment completion, treatment discontinuation, or disease recurrence. Patient outcomes were evaluated for 8 individual SF-36 health domains and 2 aggregated summary scores.

The 8 domains included in the analysis were physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, while the summary scores included PCS and MCS. The survey was scored through a norm-based scoring relative to the 2009 US general population, which yielded T-scores. Higher T-scores were indicative of better health, with the general population having a mean score of 50.

Investigators utilized a mixed model of repeated measures (MMRM) to analyze changes in SF-36 scoring from baseline through week 96. TTD was defined as the time from date of pre-dose randomization to the date of the first confirmed clinically important worsening, which was confirmed at a subsequent assessment or death.

“In the ADAURA trial, patients were asked out to fill out PRO questionnaires,” Majem explained. “[These] are questionnaires that aren’t used in patients who don't have cancer [but] in those who are in normal condition. This is a questionnaire that evaluates functional, physical, and psychological conditions of patients. It's a very [broad] questionnaire that gave us a lot of information on all these domains.”

Although the questionnaires were not cancer-specific, SF-36 has been used to assess HRQoL over a period of 4 weeks in patients who are cancer free following surgery.

Additional data indicated that health domain T-scores were comparable between patients who received osimertinib and those who received placebo. Most patients were comparable with the general population (within ±0.3 DR of the normative mean). However, investigators noted lower T-scores in role-physical, social functioning, and role-emotional domains (0.4-0.9 SD below the normative mean).

MMRM adjusted mean change in SF-36 health domain T scores for patients who were treated with osimertinib included 0.53 (95% CI, -0.10-1.16) for physical functioning, 2.67 (95% CI, 1.91-3.43) for role-physical, 1.66 (95% CI, 0.91-2.40) for bodily pain, -0.41 (-1.12-0.31) for general health, 0.98 (95% CI, 0.22-1.74) for vitality, 2.77 (95% CI, 2.06-3.49) for social functioning, 1.05 (95% CI, 0.22-1.87) for role-emotional, and 1.17 (95% CI, 0.44-1.90) for mental health.

In the placebo arm, changes included 1.38 (95% CI, 0.74-2.03) for physical functioning, 4.47 (95% CI, 3.69-5.25) for role-physical, 2.22 (95% CI, 1.45-2.99) for bodily pain, 1.09 (95% CI, 0.36-1.83) for general health, 2.91 (95% CI, 2.13-3.69) for vitality, 3.88 (3.14-4.62) for social functioning, 2.51 (95% CI, 1.66-3.36) for role-emotional, and 2.05 (95% CI, 1.30-2.80) for mental health.

Data from the PROs analysis further support adjuvant osimertinib as a novel treatment strategy in patients with 

1. Majem M, Goldman JW, John T, et al. Patient-reported outcomes from ADAURA: osimertinib as adjuvant therapy in patients with resected EGFR mutated (EGFRm) NSCLC. Abstract presented at: 2020 World Conference on Lung Cancer; January 28-31, 2021; Virtual. Accessed January 29, 2021. 

2. Additional ADAURA analyses help support the benefit of adjuvant osimertinib in patients with resected EGFR-mutated NSCLC. News release. IASLC. January 27, 2021. Accessed January 29, 2021. 

3. FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. News release. December 18, 2020. Accessed January 29, 2021. 

Patient-reported outcomes from the phase 3 ADAURA trial showed that adjuvant osimertinib maintained health-related quality of life compared with placebo in patients with EGFR-positive non–small cell lung cancer. 

PROs Show Adjuvant Osimertinib Maintains HRQoL in EGFR+ NSCLC

-amplified or -overexpressed non–small cell lung cancer (NSCLC) and MET resistance treated with osimertinib (Tagrisso) in combination with savolitinib (AZD6094) may be able to overcome resistance, according to final analysis findings presented during the 2020 World Conference on Lung Cancer.

In part B of the trial, which had 3 cohorts, results showed that the overall response rate (ORR) was 33% (95% CI, 22%-46%) in cohort 1, in which patients had received a prior third-generation EGFR TKI. Cohort 2, in which patients did not have a prior third-generation EGFR TKI and were T790M-negative, showed an ORR of 65% (95% CI, 50%-78%).

In cohort 3, where patients had no prior third-generation EGFR TKI and were T790M-positive, the ORR was 67% (95% CI, 41%-87%). Overall, in part B, the ORR was 68%.

Lastly, in patients who were included in part D of the study, with no prior third-generation EGFR TKIs and were T790M-negative, the ORR was 62% (95% CI, 46%-76%).

Patients enrolled on the part B portion experienced a median progression-free survival (PFS) of 5.5 months (95% CI, 4.1-7.7), 9.1 months (95%, 5.5-12.8), and 11.1 months (95% CI, 4.1-22.1) in cohorts 1 through 3, respectively, with an overall median PFS of 7.6 months (95% CI, 5.5-9.2). In part D of the study, the median PFS was 9.0 months (95% CI, 5.6-12.7).

The regimen was also found to be safe among the population.

"Osimertinib plus savolitinib was generally well tolerated,” lead study author Ji-Youn Han, MD, a medical oncologist at the National Cancer Center Korea, said during a virtual presentation on the data. “The 300 mg dose in part D [elicited] a slightly improved safety profile with similar antitumor activity [compared with the 600-mg dose]."

While EGFR TKIs are generally recommended for the first-line treatment of patients with locally advanced or metastatic 

-mutated NSCLC, resistance likely occurs.2-5 Preliminary data have indicated that osimertinib, a third-generation oral EGFR TKI, and savolitinib, an oral MET TKI, may be able to overcome 

-amplifiedor -overexpressed resistance to EGFR TKIs.

In the expansion cohorts of the 4-part, open-label, multicenter, phase 1b TATTON trial, investigators examined the safety and efficacy of osimertinib combined with savolitinib in this patient population.

To be eligible for enrollment, patients needed to be 18 years or older, with the exception of patients from Japan, who needed to be aged 20 years or older. Moreover, patients needed to have been diagnosed with locally advanced or metastatic 

 overexpression or amplifications needed to be confirmed by fluorescence in situ hybridization, immunohistochemistry, or next-generation sequencing and retrospective central confirmation. A World Health Organization performance status of 0 or 1 was required.

Those who enrolled in the part B cohorts were administered osimertinib at 80 mg daily along with 600 mg (n = 130) or 300 mg (n = 8) of savolitinib daily, according to weight-based dosing. Patients enrolled in the part D cohort (n = 42) were given the same dosing of osimertinib as the part B cohorts, but 300 mg daily of savolitinib.

The primary objective of the study was to evaluate the safety and tolerability of the combination, with key secondary end points consisting of ORR, PFS, and pharmacokinetics. The data cut-off date was March 4, 2020.

The majority of patients enrolled in both parts B and D of the study were female (59% and 60%, respectively) at a median age of 59 years in the part B cohorts and 63 in the part D cohort. In the part B cohorts, 72% of patients were Asian and 28% were white, whereas in the part D cohort, 67% were Asian and 33% were white. Sixty-three percent of patients in the part B cohort had an ECOG performance status of 1 and 37% had a status of 0; these rates were 64% and 36% of patients in the part D cohort, respectively.

In the part B cohorts, patients received 1 (32%), 2 (30%), 3 (16%), or more than 3 (22%) prior lines of therapy. Whereas in the part D cohort, 67% had received 1 prior line of therapy, 14% received 2, 12% received 3, and 7% more than 3 lines of therapy.

Additional data indicated that 49% of patients in the part B cohorts experienced partial responses (PRs) to the combination. Thirty-four percent of patients achieved stable disease (SD), 8% experienced progressive disease (PD), and 9% were not evaluable. In these cohorts, the combination elicited a disease control rate (DCR) of 83%, as well as a median duration of response (DOR) of 9.8 months (95% CI, 6.9-12.9).

Moreover, in the part D cohort, 62% of patients experienced a PR, 31% achieved SD, 2% experienced PD, and 5% were not evaluable. Patients in this cohort had a DCR of 93% and a median DOR of 9.7 months (95% CI, 4.5-14.3).

Additionally, Han explained, "The pharmacokinetics data for savolitinib and osimertinib were quite consistent with other patient populations in TATTON and previous clinical trials.”

Regarding safety, nearly all patients across cohorts part B and D experienced any-grade adverse effects (AE; 100% and 98%, respectively). AEs leading to death occurred in 5% each of patients in the part B and part D cohorts. The most common serious any-grade AEs in the part B cohorts included pneumonia (5%), anaphylactic reaction (4%), pneumothorax (4%), pyrexia (4%), and dyspnea (4%). In part D, common serious any-grade AEs included pneumonia (10%), pulmonary embolism (5%), anaphylactic reaction (2%), pneumothorax (2%), drug hypersensitivity (2%), and diarrhea (2%).

The most common grade 3 or higher AEs causally related to savolitinib in the part B cohort included decreased neutrophil count (7%), aspartate aminotransferase (AST) increases (6%), and alanine aminotransferase (ALT) increases (5%). In part D, this included drug hypersensitivity (7%), diarrhea (5%), generalized edema (5%), and myalgia (5%).

Osimertinib-related AEs that were grade 3 or higher included decreased neutrophil count (6%), ALT increases (4%), and AST increases (4%) in the part B cohort, and diarrhea (5%) drug hypersensitivity (5%), and myalgia (5%) in the part D cohort.

The efficacy of osimertinib plus savolitinib will be further explored in this patient population through the global phase 2 SAVANNAH trial (NCT03778229), as well as the phase 2 biomarker-directed ORCHARD study (NCT03944772).

1. Han JY, Sequist LV, Ahn MJ, et al. Osimertinib + savolitinib in patients with EGFRm MET-amplified/overexpressed NSCLC: Phase Ib TATTON Parts B and D final analysis. Poster presented at: 2021 World Conference on Lung Cancer Singapore; January 28-21, 2021; Virtual. https://bit.ly/3cl7QRE

2. Metastatic non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. ESMO. Updated September 15, 2020. Accessed January 28, 2020. https://bit.ly/3j1Z2Bt

3. Oxnard GR, Hu Y, Mileham KF, et al. Assessment of resistance mechanisms and clinical implications in patients With EGFR T790M-positive lung cancer and acquired resistance to osimertinib. 

. 2018;4(11):1527-1534. doi:10.1001/jamaoncol.2018.2969

4. Papadimitrakopoulou VA, Wu YL, Han JY, Analysis of resistance mechanisms to osimertinib in patients with EGFR T790M advanced NSCLC from the AURA3 study. 

. 2018;29:viii741. doi:10.1093/annonc/mdy424.064

5. Piotrowska Z, Isozaki H, Lennerz JK, et al. Landscape of acquired resistance to osimertinib in EGFR-mutant NSCLC and clinical validation of combined EGFR and RET inhibition with osimertinib and BLU-667 for acquired RET fusion. 

. 2018;8(12):1529-1539. doi:10.1158/2159-8290.CD-18-1022

Patients with EGFR-mutant, MET-amplified or -overexpressed non–small cell lung cancer and MET resistance treated with osimertinib  in combination with savolitinib may be able to overcome resistance, according to final analysis findings.

Hayley Virgil | Authors

Articles

Axi-Cel Shows Activity in Relapsed/Refractory DLBCL Regardless of Chemo Sensitivity

High CR Achieved With Addition of N-803 to BCG in BCG-Unresponsive NMIBC CIS

PROs Show Adjuvant Osimertinib Maintains HRQoL in EGFR+ NSCLC

Osimertinib Plus Savolitnib May Address MET Resistance in EGFR+, MET-Amplified NSCLC