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Suresh S. Ramalingam
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MA01 - Novel Systemic Treatment in NSCLC (ID 102)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 11:45 - 12:45, Scientific Program Auditorium
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MA01.09 - Efficacy and Safety of Glembatumumab Vedotin in Patients With Advanced or Metastatic Squamous Cell Carcinoma of the Lung (PrECOG 0504) (ID 1122)
11:45 - 12:45 | Author(s): Suresh S. Ramalingam
- Abstract
- Presentation
Introduction
Glycoprotein nmb (gp-NMB) is a transmembrane protein expressed in a variety of cancers; it has been linked with poor prognosis. The majority of patients with squamous lung cancer have high cellular expression of gp-NMB. Glembatumumab vedotin is an antibody-drug conjugate targeting gp-NMB.
Methods
We conducted a phase I study to determine the maximum tolerated dose of glembatumumab vedotin in patients with squamous lung cancer who expressed gp-NMB. Eligible patients had an ECOG performance status of 0-1 and progressed on any number of prior therapies. Those with treated brain metastases were eligible. The primary objective was to determine the safety and tolerability of glembatumumab vedotin in this population. Each dose cohort was planned to consist of 3-6 patients.
Results
13 patients were enrolled (for patient details see table): 9 at dose level 1, 3 at dose level -1 then 1 patient was re-escalated to dose level 1. The median number of cycles received was 2 (range 1-18). Median overall survival was 5.7 months (95% CI: 2.2-16.8), and median progression free survival was 3.6 months (95% CI: 1.6-12.4).
Using RECIST 1.1, at dose level -1 one patient achieved partial response which progressed after 17 m. Stable disease was the best response for 10 patients, with 8 progressing and 2 unevaluable.
In the first 6 patients one DLT of respiratory failure (complicated by progressive cancer) led to an additional 3 patients being enrolled to dose level 1. An additional DLT of treatment related grade 3 pruritus led to the 3 patients being enrolled on dose level -1 before resuming dose level 1.
Adverse events (AE) of any grade seen in 15% of patients were dyspnea, neutropenia, respiratory failure, anemia, >AST/ALT, diarrhea, hypophosphatemia. No AEs were seen at a frequency more than 23%; these were decreased appetite, fatigue, rash, weight loss. The only Grade 5 events were 2 respiratory failure (one partially and one completely attributed to cancer progression). Another Grade 5 event was solely “disease progression”.
Conclusion
The recommended dose for phase 2 studies was 1.9mg/kg. Modest anti-cancer activity was observed in this heavily pretreated patient population. Targeting gpNMB is feasible, although this strategy with glembatumumab had limited activity in squamous cell lung cancer patients. The phase 2 portion of the study was not undertaken due to the company’s decision to discontinue further development of this drug.
Table: Patient demographics and details
Variable
N=13
%
Age (median, range)
63 yr (52-75)
Sex
Female
6
46
Male
7
54
Race
Asian
1
8
White
11
85
Not specified
1
8
Histology
Adenosquamous
2
17
Squamous
10
83
Unknown
1
8
Stage
IIIB
1
8
IV
11
92
ECOG PS
0
2
15
1
11
85
Prior lines of trt
1
5
42
2
4
33
>=3
3
25
Prior nonbrain XRT
No
3
25
Yes
9
75
Prior brain XRT for NSCLC
No
10
83
Yes
2
17
Prior surgery for NSCLC
No
6
50
Yes
6
50
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OA04 - New Data from Rare EGFR Alterations (ID 223)
- Event: WCLC 2020
- Type: Oral
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 11:45 - 12:45, Scientific Program Auditorium
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OA04.03 - Mobocertinib in NSCLC With EGFR Exon 20 Insertions: Results From EXCLAIM and Pooled Platinum-Pretreated Patient Populations (ID 3186)
11:45 - 12:45 | Author(s): Suresh S. Ramalingam
- Abstract
- Presentation
Introduction
Mobocertinib is a potent first-in-class tyrosine kinase inhibitor (TKI) designed to target EGFR exon 20 insertion (EGFRex20ins) mutations. We report first results from the EXCLAIM extension cohort of a phase 1/2 study (NCT02716116) and results in patients with EGFRex20ins-mutant NSCLC who received prior platinum-based therapy from the dose-escalation/expansion parts of the study and the EXCLAIM extension cohort.
Methods
This 3-part, open-label, multicenter study included dose-escalation/expansion cohorts and the EXCLAIM extension cohort. Data are presented for all patients treated in EXCLAIM (N=96) and for platinum-pretreated patients from the dose-escalation/expansion cohorts (n=28) and from EXCLAIM (n=86); all received mobocertinib 160 mg orally QD. Enrolled patients had locally advanced/metastatic EGFRex20ins NSCLC, ECOG performance status 0–1, and ≥1 prior line of therapy for locally advanced/metastatic disease. The primary endpoint is confirmed ORR assessed by IRC per RECIST v1.1.
Results
In EXCLAIM, 96 patients were enrolled and treated; median age, 59 years [range: 27–80]; female, 65%; Asian, 69%; ≥2 prior systemic anticancer lines, 49% (range: 1–4). Median time on treatment was 6.5 months (range: 0–14). Confirmed ORR was 23% (22/96; 95% CI: 15%–33%) per IRC and 32% (95% CI: 23%–43%) per investigator; median DoR (Kaplan-Meier estimates) was not mature; median PFS was 7.3 months. See Table. In the analysis of platinum-pretreated patients (n=114), median age, 60 years [range: 27–84]; female, 66%; Asian, 60%; ≥2 prior systemic anticancer lines, 59% (range: 1–7). Median time on treatment was 7 months (range: 0–31); 38 patients (33%) remained on treatment as of 29-May-2020. Confirmed ORR was 26% (30/114; 95% CI: 19%–35%) per IRC and 35% (40/114; 26%–45%) per investigator. Median PFS was 7.3 months: 12-month PFS rate was 33% (95% CI: 21%–47%). Responses were observed among all prespecified subgroups, including Asian/non-Asian patients and those with/without baseline stable brain metastases. The most common treatment-related adverse events (TRAEs; ≥30%): diarrhea (90%), rash (45%), paronychia (34%), nausea (32%), decreased appetite (32%), dry skin (30%), and vomiting (30%); grade ≥3 TRAEs (≥5%): diarrhea (22%), anemia (5%), and dyspnea (5%). Nineteen patients (17%) discontinued due to AEs, most commonly diarrhea (4%) and nausea (4%). The safety profile observed in EXCLAIM was largely consistent with that observed in the platinum-pretreated population.
Conclusion
Mobocertinib demonstrated clinically meaningful benefit in previously treated patients with NSCLC and EGFRex20ins mutations, with a manageable safety profile.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.05 - Radiotherapy with Concurrent Versus Sequential Osimertinib for Advanced Non-Small Cell Lung Cancer: a Multi-Center Toxicity Analysis (ID 874)
00:00 - 00:00 | Author(s): Suresh S. Ramalingam
- Abstract
Introduction
The third-generation, irreversible tyrosine kinase inhibitor osimertinib is first-line treatment for advanced non-small cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR). Pre-clinical studies have shown synergistic anti-tumor activity of osmertinib and radiotherapy. However, the safety of radiotherapy with concurrent osimertinib has not been reported.
Methods
Medical records of all patients with EGFR-mutated NSCLC who received radiotherapy and osimertinib at an academic hospital system were reviewed. Thirty-five patients received 46 courses of radiotherapy while taking osimertinib, and 27 patients received 33 courses of radiotherapy followed by osimertinib; all patients in the latter group began taking osimertinib within 30 days of completing radiotherapy. Patients treated by radiotherapy and osimertinib at unrelated time points of disease progression were excluded. Toxicity grades experienced during radiation treatment (per Common Terminology Criteria for Adverse Events v5.0) were compared between patients who received concurrent versus sequential osimertinib.
Results
This series consists of 40 females and 22 males with advanced lung adenocarcinomas. Radiation treatment was palliative or locally consolidative (96%) in all but 2 patients. There was a trend toward more patients with oligoprogressive disease (P=0.092) and fewer patients with poor performance status (P=0.057) treated by concurrent osimertinib. Grade ≥ 3 toxicities during radiotherapy did not significantly differ between those who received osimertinib concurrently versus sequentially (7% versus 3%, P=0.859). Patients who received concurrent osimertinib had inferior progression-free survival (PFS) (HR 2.62, 95% CI 1.09–6.29, P=0.031) and similar overall survival (HR 1.39, 95% CI 0.40–4.81, P=0.60).
Patient Characteristics
Concurrent (%)
N=35
Sequential (%)
N=27
P
Median age, years
60 (range 40–76)
60 (range 38–80)
0.740
Sex
0.563
· Female
21 (60)
19 (70)
· Male
14 (40)
8 (30)
Smoking status
0.469
· Never
23 (66)
14 (52)
· Former
11 (31)
11 (41)
· Current
1 (3)
2 (7)
ECOG
0.057
· 0
11 (31)
10 (37)
· 1
16 (46)
10 (37)
· 2
8 (23)
2 (7)
· 3
0 (0)
4 (15)
· 4
0 (0)
1 (4)
Oligoprogressive disease
19 (54)
8 (30)
0.092
T classification
0.503
· T1
6 (17)
9 (33)
· T2
16 (46)
11 (41)
· T3
7 (20)
4 (15)
· T4
6 (17)
3 (11)
N classification
0.604
· N0
11 (31)
10 (37)
· N1
4 (11)
1 (4)
· N2
17 (49)
12 (44)
· N3
3 (9)
4 (15)
M classification
0.107
· M0
1 (3)
1 (4)
· M1a
7 (20)
0 (0)
· M1b
4 (11)
4 (15)
· M1c
23 (66)
22 (81)
Primary lung tumor lobe
0.286
· LUL
8 (23)
5 (19)
· LLL
7 (20)
1 (4)
· RUL
11 (31)
14 (52)
· RML
2 (6)
1 (4)
· RLL
7 (20)
6 (22)
EGFR mutation
0.400
· Exon 19 deletion
16 (46)
10 (37)
· L858R
12 (34)
9 (33)
· T790M
12 (34)
6 (22)
· Other
3 (9)
6 (22)
Osimertinib dose per day
0.715
· 80 mg
33 (94)
26 (96)
· 40 mg
2 (6)
1 (4)
Irradiated metastatic sites
0.116
· Lung/mediastinum
8 (23)
0 (0)
· Brain
14 (40)
16 (59)
· C spine
2 (6)
0 (0)
· T spine
2 (6)
2 (7)
· L spine
2 (6)
4 (15)
· Non-spinous bone
13 (37)
9 (33)
· Adrenal gland
1 (3)
0 (0)
· Liver
2 (6)
3 (11)
· Distant lymph node
0 (0)
1 (4)
Median follow-up, months
6 (range 0–27)
5 (range 1–42)
0.426
Conclusion
Treatment with radiotherapy and concurrent osimertinib confers acceptable acute toxicity. This finding is clinically significant, as delaying or holding osimertinib during radiotherapy may adversely impact disease control. The observed PFS benefit of sequential osimertinib is likely driven by selection bias for osimertinib-naїve patients whose disease has not yet been under evolutionary pressure to acquire resistance, compared to those already on osimertinib.
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P77 - Immunotherapy (Phase II/III Trials) - Combining Different Immunotherapeutic Approaches (ID 254)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P77.04 - PROPEL: A Phase 1/2 Trial of Bempegaldesleukin (NKTR-214) Plus Pembrolizumab in Lung Cancer and other Advanced Solid Tumors (ID 1548)
00:00 - 00:00 | Author(s): Suresh S. Ramalingam
- Abstract
Introduction
Checkpoint inhibitors (CPIs), are now part of standard treatment in many advanced solid tumors, including metastatic non-small cell lung cancer (NSCLC). However, novel, more effective CPI combinations are needed to broaden, deepen, and prolong responses, especially for patients with poor prognostic features or negative predictive clinical factors for CPI benefit, including programmed death-ligand 1-negative (PD-L1[-]) status. Bempegaldesleukin (BEMPEG; NKTR-214) is a first-in-class CD122-preferential interleukin-2 pathway agonist that directly activates and expands effector T cells and natural killer cells over immunosuppressive regulatory T cells. BEMPEG plus CPI combination has demonstrated promising efficacy and can convert PD-L1(-) tumors to PD-L1(+) in patients with various solid tumors.(1,2) Given the early efficacy data and favorable safety profile of BEMPEG plus nivolumab, PROPEL will evaluate the clinical benefit, safety and tolerability of BEMPEG combined with another CPI, pembrolizumab (PEMBRO). Here, we present the updated methodology and protocol for the enrolling PROPEL study.(3)
Methods
This phase 1/2 multinational trial evaluates BEMPEG plus PEMBRO in patients with locally advanced or metastatic solid tumors. During dose escalation (US only), ~40 patients with various advanced solid tumors (first- and second-line melanoma, NSCLC, urothelial carcinoma, head and neck squamous cell carcinoma, and hepatocellular carcinoma; regardless of PD-L1 status) will be treated with escalating doses of BEMPEG plus PEMBRO according to a 3+3 or step-up design. During dose expansion (global), ~58 patients with previously untreated advanced or metastatic NSCLC will be enrolled, and stratified based on PD-L1 status (<1%, 1-49%, and >50% staining on tumor cells by immunohistochemistry [for France only, patients with PD-L1 ≤49% will be excluded]). The primary objectives of the dose escalation are to evaluate safety and tolerability and determine the maximum tolerated dose/recommended phase 2 dose for BEMPEG in combination with PEMBRO. The primary objective of the dose expansion is objective response rate (by RECIST 1.1) in first-line metastatic NSCLC. Enrollment is ongoing (NCT03138889).
References: 1. Diab A, et al. J Immunotherapy Canc 2019;7(1 suppl):3006; 2. Siefker-Radtke A, et al. J Clin Oncol 2019;37(7 suppl):388; 3. Reck M, et al. Poster presented at ESMO 2019; Poster 127TiP.
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P83 - Immunotherapy (Phase II/III Trials) - Immunotherapy Plus Targeted Therapy (ID 260)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P83.02 - Niraparib + Pembrolizumab (Pembro) Versus Placebo + Pembro 1L Maintenance Therapy in Advanced NSCLC: ZEAL-1L Phase III Study (ID 3405)
00:00 - 00:00 | Presenting Author(s): Suresh S. Ramalingam
- Abstract
Introduction
The poly (ADP-ribose) polymerase (PARP) inhibitor niraparib exerts antitumor activity primarily by impairing the ability of cells to repair DNA damage via the homologous recombination repair pathway. Preclinical data suggests that niraparib may also activate the stimulator of interferon gene (STING) pathway, recruit T cells, and upregulate programmed cell death ligand-1 (PD-L1) in some cancers. Accordingly, the potential synergistic antitumor effect of niraparib and the programmed cell death 1 inhibitor pembro has been observed, along with a tolerable safety profile, in the Phase II TOPACIO/KEYNOTE-162 (NCT02657889) trial of patients with triple-negative breast cancer and platinum-resistant ovarian cancer (Vinayak et al. JAMA Oncol 2019). Early results of the Phase II JASPER (NCT03308942) trial in locally advanced and metastatic NSCLC suggest that this combination is active and well tolerated as first-line (1L) therapy. Maximizing treatment efficacy is important in this setting, as progression-free survival (PFS) is limited to <9 months with standard-of-care chemotherapy plus pembro, and patients with recurrent disease have few treatment options.
The objective of the Phase III ZEAL-1L study is to compare the efficacy and safety of maintenance niraparib plus pembro versus placebo plus pembro, following 1L therapy, in patients with advanced/metastatic NSCLC without known driver mutations.
Methods
ZEAL-1L is a Phase III randomized, double-blind, global, multicenter trial of niraparib plus pembro versus placebo plus pembro in patients with Stage IIIB–IV NSCLC that has not progressed (stable disease [SD], with partial or complete response [PR or CR]) after 4–6 cycles of 1L induction platinum-based chemotherapy plus pembro. Patients with controlled, asymptomatic brain metastasis can participate. Approximately 650 participants will be recruited.
The dual primary objectives of the study are to evaluate radiographic PFS as assessed by blinded independent central radiology review (BICR) per Response Evaluation in Solid Tumors (RECIST v1.1) criteria and overall survival for patients treated with niraparib plus pembro versus placebo plus pembro. Participants will be stratified by histology (squamous vs non-squamous), PD-L1 status (tumor cells [TC] <1% vs TC ≥1%), and best response to induction therapy (SD vs PR/CR). Niraparib crosses the blood–brain barrier in preclinical models; therefore, the key secondary objective is time to progression in the central nervous system as assessed by BICR using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Patient-reported outcomes, safety, and pharmacokinetic profiles will also be evaluated.
Participants will be randomized (1:1) to niraparib (200 or 300 mg, orally, daily, depending on body weight) or placebo. Treatment will continue until disease progression, unacceptable toxicity or death, or for up to 3 years. All patients will continue on pembro (200 mg intravenously on Day 1 of each 21-day cycle) up to a maximum of 35 cycles from the beginning of induction therapy. Study (recruitment) start date: September 2020.
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PS01 - Presidential Symposium (Japanese, Mandarin, Spanish Translation Available) (ID 143)
- Event: WCLC 2020
- Type: Plenary
- Track: N.A.
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 07:00 - 09:00, Scientific Program Auditorium
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PS01.07 - CodeBreaK 100: Registrational Phase 2 Trial of Sotorasib in KRAS p.G12C Mutated Non-small Cell Lung Cancer (ID 3037)
07:00 - 09:00 | Author(s): Suresh S. Ramalingam
- Abstract
- Presentation
Introduction
Outcome in patients with advanced non-small cell lung cancer (NSCLC) on second- or third-line therapies is poor, with a response rate of <20% and median progression-free survival (PFS) of <4 months. Approximately 13% of patients with lung adenocarcinomas harbor KRAS p.G12C mutation. Sotorasib is a first-in-class small molecule that specifically and irreversibly inhibits KRASG12C. In the phase 1 cohort of the CodeBreaK 100 trial (NCT03600883), sotorasib was well tolerated and demonstrated a confirmed response rate of 32.2%, a median duration of response (DoR) of 10.9 months, and a median PFS of 6.3 months in patients with heavily pretreated NSCLC. Here, we present for the first time the primary analysis from the registrational phase 2 portion of the trial.
Methods
This international, single-arm, phase 2 study evaluated the efficacy and safety of sotorasib, administered orally once daily at 960 mg, in the cohort of patients with locally advanced or metastatic KRAS p.G12C mutant NSCLC. Key inclusion criteria: centrally confirmed KRAS p.G12C; progression on anti-PD-1/PD-L1 immunotherapy and/or platinum-based combination chemotherapy, and targeted therapy if EGFR, ALK, and ROS1 alterations were identified; and ≤3 prior lines of therapy. Patients with untreated active brain metastases were excluded. Primary endpoint was confirmed objective response rate (ORR), assessed by blinded independent central review per RECIST 1.1. Key secondary endpoints included disease control rate (DCR), PFS, DoR, and safety.
Results
Data cutoff was September 1, 2020. A total of 126 patients were enrolled and received at least 1 dose of sotorasib. Median follow-up time on study was 9.3 months (range: 1.1+ to 12.2). Median age was 63.5 years (range: 37 to 80), and 117 (92.9%) were former or current smokers. 72 (57.1%) patients received 2 or 3 prior lines of anticancer therapy. 91.3% received anti-PD-1/PD-L1 immunotherapy, and 81.0% received both platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy. Per central review, 123 patients had at least 1 measurable lesion at baseline and were evaluated for efficacy. 46 patients experienced a confirmed response (2 complete responses and 44 partial responses), resulting in an ORR of 37.4% (95% Cl: 28.8–46.6). At a median follow-up of 6.9 months for DoR, 52.2% of responders remained on treatment without progression. DCR was 80.5% (95% Cl: 72.4–87.1). Median PFS was 6.7 months (95% Cl: 4.9–8.1). Treatment-related adverse events (TRAEs) of any grade occurred in 88 (69.8%) patients and led to discontinuation in 9 (7.1%) patients. Grade ≥3 TRAEs were reported in 26 (20.6%) patients; those that occurred in >3% of patients were alanine aminotransferase increase (8/126, 6.3%), aspartate aminotransferase increase (7/126, 5.6%), and diarrhea (5/126, 4.0%). No fatal TRAEs were reported.
Conclusion
In the phase 2 CodeBreaK 100 trial, sotorasib provided deep responses and durable clinical benefit with a favorable safety profile in patients with pretreated NSCLC harboring KRAS p.G12C, validating the previous phase 1 results. After four decades of scientific effort, sotorasib may have the potential to be the first targeted treatment option for this patient population with a high unmet need. Updated data including DoR, PFS, and biomarkers will be presented.
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PS02 - Presidential Symposium (Re-Broadcast) (Japanese, Mandarin, Spanish Translation Available) (ID 275)
- Event: WCLC 2020
- Type: Plenary
- Track: N.A.
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 18:00 - 20:00, Scientific Program Auditorium
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PS02.07 - CodeBreaK 100: Registrational Phase 2 Trial of Sotorasib in KRAS p.G12C Mutated Non-small Cell Lung Cancer (ID 4290)
18:00 - 20:00 | Author(s): Suresh S. Ramalingam
- Abstract
Introduction
Outcome in patients with advanced non-small cell lung cancer (NSCLC) on second- or third-line therapies is poor, with a response rate of <20% and median progression-free survival (PFS) of <4 months. Approximately 13% of patients with lung adenocarcinomas harbor KRAS p.G12C mutation. Sotorasib is a first-in-class small molecule that specifically and irreversibly inhibits KRASG12C. In the phase 1 cohort of the CodeBreaK 100 trial (NCT03600883), sotorasib was well tolerated and demonstrated a confirmed response rate of 32.2%, a median duration of response (DoR) of 10.9 months, and a median PFS of 6.3 months in patients with heavily pretreated NSCLC. Here, we present for the first time the primary analysis from the registrational phase 2 portion of the trial. Methods
This international, single-arm, phase 2 study evaluated the efficacy and safety of sotorasib, administered orally once daily at 960 mg, in the cohort of patients with locally advanced or metastatic KRAS p.G12C mutant NSCLC. Key inclusion criteria: centrally confirmed KRAS p.G12C; progression on anti-PD-1/PD-L1 immunotherapy and/or platinum-based combination chemotherapy, and targeted therapy if EGFR, ALK, and ROS1 alterations were identified; and ≤3 prior lines of therapy. Patients with untreated active brain metastases were excluded. Primary endpoint was confirmed objective response rate (ORR), assessed by blinded independent central review per RECIST 1.1. Key secondary endpoints included disease control rate (DCR), PFS, DoR, and safety. Results
Data cutoff was September 1, 2020. A total of 126 patients were enrolled and received at least 1 dose of sotorasib. Median follow-up time on study was 9.3 months (range: 1.1+ to 12.2). Median age was 63.5 years (range: 37 to 80), and 117 (92.9%) were former or current smokers. 72 (57.1%) patients received 2 or 3 prior lines of anticancer therapy. 91.3% received anti-PD-1/PD-L1 immunotherapy, and 81.0% received both platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy. Per central review, 123 patients had at least 1 measurable lesion at baseline and were evaluated for efficacy. 46 patients experienced a confirmed response (2 complete responses and 44 partial responses), resulting in an ORR of 37.4% (95% Cl: 28.8–46.6). At a median follow-up of 6.9 months for DoR, 52.2% of responders remained on treatment without progression. DCR was 80.5% (95% Cl: 72.4–87.1). Median PFS was 6.7 months (95% Cl: 4.9–8.1). Treatment-related adverse events (TRAEs) of any grade occurred in 88 (69.8%) patients and led to discontinuation in 9 (7.1%) patients. Grade ≥3 TRAEs were reported in 26 (20.6%) patients; those that occurred in >3% of patients were alanine aminotransferase increase (8/126, 6.3%), aspartate aminotransferase increase (7/126, 5.6%), and diarrhea (5/126, 4.0%). No fatal TRAEs were reported. Conclusion
In the phase 2 CodeBreaK 100 trial, sotorasib provided deep responses and durable clinical benefit with a favorable safety profile in patients with pretreated NSCLC harboring KRAS p.G12C, validating the previous phase 1 results. After four decades of scientific effort, sotorasib may have the potential to be the first targeted treatment option for this patient population with a high unmet need. Updated data including DoR, PFS, and biomarkers will be presented.
