On September 11, 2023 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM" or the "Company") reported that Roswell Park Comprehensive Cancer Center has announced the complete topline data from its Phase 1 study evaluating Ampligen (rintatolimod) as a component of a CKM regimen for the treatment of early-stage triple negative breast cancer (TNBC) (Press release, AIM ImmunoTech, SEP 11, 2023, View Source [SID1234635053]). The complete topline results are now available on ClinicalTrials.gov: NCT04081389.

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The research was led by Roswell Park Comprehensive Cancer Center medical oncologist Shipra Gandhi, MD, a physician scientist who is Assistant Professor of Oncology at Roswell Park, in collaboration with senior investigator Pawel Kalinski, MD, PhD, Chair of Immunology and Senior Vice President for Team Science at Roswell Park.

The now completed topline results from the Phase 1 study confirm the positive findings that were previously presented at the 2022 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting in a poster presentation titled Safety and efficacy of de-escalated neoadjuvant chemoimmunotherapy of triple negative breast cancer (TNBC) using chemokine-modulating regimen (rintatolimod, IFN-α2b, celecoxib)1.

"We are pleased to bolster our growing body of data from Ampligen and the results demonstrated in the Phase 1 study with the completed topline data report now in hand. We continue to be encouraged by Ampligen’s demonstrated potential to deliver promising clinical activity in an area where there remain significant immune-related toxicities with the current standard of care and look forward to its continued development," stated David Strayer, MD, AIM’s Chief Scientific and Medical Officer.

In the Phase 1 study, 9 patients with stage I-III TNBC, median age 47 (37-55) years, were treated with paclitaxel 80 mg/m2 IV weekly for 12 weeks and CKM for the first 3 weeks, days 1-3 (IV Ampligen 200 mg daily and oral celecoxib 200 mg twice daily). IFN-α2b was administered in an accelerated dose-escalation at 0 or 5 million units (MU)/m2 [dose levels (DL) 1,2 respectively] in the first 2 patients; 10 MU/m2 [DL 3] in 4 patients and 20 MU/m2 [DL 4] in 3 patients. CKM/paclitaxel was followed by standard dose-dense doxorubicin and cyclophosphamide (AC) and surgery.

The primary endpoint of the study was safety and tolerability. The results demonstrated that treatment was well-tolerated with mostly grade 1 or 2 treatment-related adverse events (TRAEs) without dose-limiting toxicities (DLTs) or delayed or immune-related toxicities. DLT was defined as grade 3 or higher toxicities within the first 3 weeks. Secondary endpoints included pCR rate where 5/9 (56%) of patients attained pCR and 1 more patient attained ypTmic. Tumor and blood biomarkers were also analyzed in exploratory studies.

For more information about the Phase 1 study, visit ClinicalTrials.gov: NCT04081389.

On September 11, 2023 ADC therapeutics presented its corporate presentation (Presentation, ADC Therapeutics, SEP 11, 2023, View Source [SID1234635052]).

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On September 9, 2023 AstraZeneca reported that Positive results from the FLAURA2 Phase III trial showed Tagrisso (osimertinib) in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), compared to Tagrisso alone for patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC).

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These results were presented today in a Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC) (abstract #PL03).

Results showed Tagrisso plus chemotherapy reduced the risk of disease progression or death by 38% compared to Tagrisso alone (based on a hazard ratio [HR] of 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). By investigator assessment, the combination extended median PFS by 8.8 months versus Tagrisso alone. PFS results from blinded independent central review (BICR) were consistent, showing Tagrisso plus chemotherapy extended median PFS by 9.5 months (based on HR of 0.62; 95% CI 0.48-0.80; p=0.0002). Importantly, a clinically meaningful PFS benefit was observed across all prespecified subgroups, including sex, race, type of EGFR mutation, age at time of diagnosis, smoking history and central nervous system (CNS) metastases status at baseline.

At the time of this analysis, the overall survival (OS) data were immature however, a favourable trend was observed for Tagrisso plus chemotherapy.

Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial, said: "Patients received nearly nine additional months before their EGFR-mutated non-small cell lung cancer progressed as a result of the addition of chemotherapy to standard-of-care osimertinib, building on the strong efficacy we have already seen with osimertinib monotherapy. With these convincing data, patients may soon have a choice of two highly effective osimertinib-based treatment options in this advanced disease setting."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The compelling FLAURA2 results add to the extensive evidence supporting Tagrisso as the backbone therapy in EGFR-mutated non-small cell lung cancer and establish a new benchmark for progression-free survival in this setting. We look forward to bringing this potential treatment regimen to patients with advanced lung cancer to further delay disease progression, especially for patients with the greatest unmet need including those with central nervous system metastasis at diagnosis."

Summary of results: FLAURA2

PFS by INV

PFS by BICR

Tagrisso plus chemotherapy

(n=279)

Tagrisso monotherapy

(n=278)

Tagrisso plus chemotherapy

(n=279)

Tagrisso monotherapy

(n=278)

Median PFS (in months)i

25.5

(24.7, NCii)

16.7

(14.1, 21.3)

29.4

(25.1, NCii)

19.9

(16.6, 25.3)

Hazard ratio (95% CI)

0.62 (0.49-0.79)

0.62 (0.48-0.80)

p-value

<0.0001

0.0002

Data maturity

51%

43%

i. Data cut-off date was 3 April 2023.

ii. NC: Not calculable

Safety results and discontinuation rates due to adverse events (AEs) were consistent with the established profiles of each medicine and no new safety concerns were reported. Grade 3 or higher AEs from all causes occurred in 64% of patients in the Tagrisso plus chemotherapy arm versus 27% in the Tagrisso monotherapy arm.

Notes

Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and small cell lung cancer.2 Each year, there are an estimated 2.2 million people diagnosed with lung cancer globally with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.1-3 Approximately 70% of people are diagnosed with advanced NSCLC.4

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.5-7 Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells.8

FLAURA2
FLAURA2 is a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with Tagrisso 80mg once daily oral tablets in combination with chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5)) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks.

The trial enrolled 557 patients in more than 150 centres across more than 20 countries, including in the US, Europe, South America and Asia. This is the analysis of the primary endpoint of PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has been used to treat nearly 700,000 patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC.

Tagrisso, the only targeted therapy to improve survival in both early- and late-stages of EGFRm NSCLC, is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. These include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC (FLAURA), locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage (IB, II and IIIA) EGFRm NSCLC (ADAURA), where Tagrisso recently demonstrated a statistically significant and clinically meaningful OS benefit.

AstraZeneca also has several ongoing Phase III trials focused on earlier stages of lung cancer including a trial in the Stage IA2-IA3 adjuvant resectable setting (ADAURA2), and in the Stage III locally advanced unresectable setting (LAURA).

The Company is also researching ways to address tumour mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test Tagrisso plus savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.

On September 10, 2023 Daiichi Sankyo reported that Results from the HERTHENA-Lung01 phase 2 trial showed that patritumab deruxtecan (HER3-DXd) demonstrated clinically meaningful and durable responses in patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) following disease progression with an EGFR TKI and platinum-based chemotherapy (Press release, Daiichi Sankyo, SEP 10, 2023, View Source [SID1234635049]). These data were presented today during an oral presentation (OA05.03) at the 2023 World Conference on Lung Cancer (#WCLC23) and simultaneously published in the Journal of Clinical Oncology.

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Patritumab deruxtecan is a specifically engineered potential first-in-class HER3 directed antibody drug conjugate (ADC) designed using Daiichi Sankyo’s (TSE: 4568) proprietary DXd ADC technology.

NSCLC accounts for approximately 85% of all lung cancers – 55% having distant spread at diagnosis – with EGFR-activating mutations occurring in 14% to 38% of all NSCLC tumors worldwide.1,2,3 After disease progression following treatment with an EGFR TKI and platinum-based chemotherapy, currently available therapies offer limited efficacy, highlighting the need for new approaches to improve outcomes.3,4

A confirmed objective response rate (ORR) of 29.8% (95% CI: 23.9-36.2) was observed with patritumab deruxtecan (5.6 mg/kg) in 225 patients with EGFR-mutated NSCLC as assessed by blinded independent central review (BICR). One complete response (CR), 66 partial responses (PRs) and 99 cases of stable disease (SD) were seen. A median duration of response (DOR) of 6.4 months (95% CI: 4.9-7.8) and a disease control rate (DCR) of 73.8% (95% CI: 67.5-79.4) were observed. Median progression-free survival (PFS) was 5.5 months (95% CI: 5.1-5.9) and median overall survival (OS) was 11.9 months (95% CI: 11.2-13.1) as of snapshot data cutoff of May 18, 2023.

Efficacy outcomes were consistent across subgroups including a subset of 209 patients previously treated with a third-generation EGFR TKI and platinum-based chemotherapy. Anti-tumor activity with patritumab deruxtecan was observed across diverse mechanisms of EGFR TKI resistance and across a broad range of pretreatment tumor HER3 membrane expression.

In a subset of 30 patients with brain metastases at baseline and no prior radiotherapy treatment, an intracranial ORR of 33.3% (95% CI: 17.3-52.8%) was observed as assessed by central nervous system (CNS) BICR. In these patients, nine intracranial CRs, one intracranial PR and 13 cases of SD were seen. A CNS DOR of 8.4 months (95% CI: 5.8-9.2) was observed.

"The results from HERTHENA-Lung01 provide compelling evidence of efficacy of patritumab deruxtecan in heavily pretreated patients with advanced EGFR-mutated non-small cell lung cancer," said Helena Yu, MD, Associate Attending Physician, Memorial Sloan Kettering Cancer Center. "The clinically meaningful efficacy observed across a broad range of HER3 expression and diverse mechanisms of EGFR TKI resistance as well as the anti-tumor activity seen in patients with brain metastases, underscore the potential of patritumab deruxtecan to become an important treatment option for a population of patients with lung cancer who have limited treatment options."

"Disease progression is inevitable in patients with previously treated and relapsed metastatic EGFR-mutated non-small cell lung cancer, reinforcing the need for new and innovative treatments across diverse mechanisms of resistance," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "The results from HERTHENA-Lung01, coupled with early trial results, show that patritumab deruxtecan demonstrates clinically meaningful and durable responses, illustrating the potential of this HER3 directed antibody drug conjugate to become a new standard of care for this patient population with high unmet medical need. These data will support our ongoing discussions with health authorities including our planned submission in the U.S."

The safety profile of patritumab deruxtecan observed in HERTHENA-Lung01 was consistent with previous clinical trials with a low rate (7.1%) of treatment discontinuation due to treatment-emergent adverse events (TEAEs) at the time of primary data cutoff of November 21, 2022. Grade 3 or higher TEAEs occurred in 64.9% of patients. The most common (>5%) grade 3 or higher TEAEs were thrombocytopenia (21%), neutropenia (19%), anemia (14%), leukopenia (10%), fatigue (6%), hypokalemia (5%) and asthenia (5%). Twelve patients (5.3%) had confirmed treatment-related interstitial lung disease (ILD) as determined by an independent adjudication committee. The majority of ILD events were low grade with one grade 1 event and eight grade 2 events. Two grade 3, zero grade 4 and one grade 5 ILD event were observed.

In HERTHENA-Lung01, 51% of patients (n=115) had a history of CNS metastases; 32% (n=72) and 33% of patients (n=75) had brain or liver metastases at baseline by BICR, respectively. In the trial, 63% (n=142) and 36% (n=82) of patients had either an EGFR exon 19 deletion or exon 21 L858R mutation detected at baseline, respectively, and one patient had both.

Patients were heavily pretreated receiving a median of three prior lines of systemic therapy in the locally advanced/metastatic setting (range, 1-11), including platinum-based chemotherapy (100%), third generation EFGR TKI (93%) and immunotherapy (40%). As of the snapshot data cutoff of May 18, 2023, the median trial duration was 18.9 (14.9-27.5) months, and 13 patients were continuing to receive patritumab deruxtecan.

Summary of HERTHENA-Lung01 Results

Efficacy Measure

Prior treatment with any EGFR TKI and platinum-based chemotherapy

n=225

Subset with prior treatment with third-generation EGFR

TKI and platinum-based chemotherapy

n=209

Confirmed ORR, % (95% CI)

29.8% (23.9-36.2)

29.2.% (23.1-35.9)

CR, n (%)

1 (0.4%)

1 (0.5%)

PR, n (%)

66 (29.3%)

60 (28.7%)

SD, n (%)

99 (44.0%)

91 (43.5%)

PD, n (%)

43 (19.1%)

41 (19.6%)

NE, n (%)

16 (7.1%)

16 (7.7%)

DCR (95% CI), %

73.8% (67.5-79.4)

72.7% (66.2-78.6)

DOR, median (95% CI), months

6.4 months (4.9-7.8)

6.4 months (5.2-7.8)

PFS, median (95% CI), months

5.5 months (5.1-5.9)

5.5 months (5.1-6.4)

OS, median (95% CI), months

11.9 months (11.2-13.1)

11.9 months (10.9-13.1)

CR, complete response; DCR, disease control rate; DOR, duration of response; NE, not evaluable; ORR, objective response rate; OS, overall survival; PR, partial response; PFS, progression-free survival; PD, progressive disease; SD, stable disease.

About HERTHENA-Lung01
HERTHENA-Lung01 is a global, multicenter, open-label, two-arm phase 2 trial evaluating the safety and efficacy of patritumab deruxtecan in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy. Patients were randomized 1:1 to receive 5.6 mg/kg (n=225) or an uptitration regimen (n=50). The uptitration arm was discontinued as the dose of 5.6 mg/kg of patritumab deruxtecan was selected following a risk-benefit analysis conducted from the phase 1 trial assessing the doses in a similar patient population.

The primary endpoint of HERTHENA-Lung01 was ORR as assessed by BICR. Secondary endpoints included duration of response, PFS, disease control rate, and time to response – all assessed by both BICR and investigator assessment – as well as investigator-assessed ORR, OS, safety and tolerability.

The data presented at WCLC is from the first arm and based on the fixed-dose (5.6 mg/kg) regimen.

HERTHENA-Lung01 enrolled patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov.

About EGFR-Mutated Non-Small Cell Lung Cancer
Lung cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide.5 NSCLC accounts for approximately 85% of all lung cancers – 55% having distant spread at diagnosis – with EGFR mutations occurring in 14% to 38% of all NSCLC tumors worldwide.1,2,3

The introduction of targeted therapies has improved the treatment landscape for patients with EGFR-mutated locally advanced or metastatic NSCLC. Targeted therapy with EGFR TKIs offers higher response rates, PFS and potential OS advantage, compared to chemotherapy, with third generation EGFR TKIs demonstrating superior efficacy compared to earlier generation inhibitors.1 However, disease progression from resistance to EGFR TKIs inevitably occurs one to two years following initial treatment.6

After failure of EGFR TKI and platinum-based chemotherapy, currently available therapies offer limited efficacy.3,4 A recent real-world analysis of the treatment of patients in this setting showed that the median PFS in this setting is 3.3 months (95% CI: 2.8-4.4) and median OS is 8.6 months (95% CI: 7.4-9.8). An estimated real-world ORR of 14.1% (95% CI: 3.7%-33.1%) also has been observed.7,8 New treatment approaches are needed to help improve clinical outcomes in patients with EGFR-mutated NSCLC.

About HER3
HER3 is a member of the EGFR family of receptor tyrosine kinases.9 It is estimated that about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors express HER3 after prior EGFR TKI treatment.10,11 There is currently no HER3 directed therapy approved for the treatment of any cancer.

About Patritumab Deruxtecan
Patritumab deruxtecan (HER3-DXd) is an investigational HER3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, patritumab deruxtecan is composed of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Patritumab deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration in December 2021 for the treatment of patients with EGFR-mutated locally advanced or metastatic NSCLC with disease progression on or after treatment with a third-generation TKI and platinum-based therapies.

Patritumab deruxtecan is currently being evaluated as both a monotherapy and in combination with other therapies in a global development program, which includes HERTHENA-Lung02, a phase 3 trial versus platinum-based chemotherapy in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression on or after treatment with a third-generation EGFR TKI; a phase 1 trial in combination with osimertinib in EGFR-mutated locally advanced or metastatic NSCLC; and a phase 1 trial in previously treated patients with advanced NSCLC. A phase 1/2 trial in HER3 expressing metastatic breast cancer also has been completed.

On September 10, 2023 Daiichi Sankyo reported Updated results from a subgroup analysis of a phase 1/2 trial showed that ifinatamab deruxtecan (I-DXd) continues to demonstrate durable responses in patients with heavily pretreated advanced small cell lung cancer (SCLC) (Press release, Daiichi Sankyo, SEP 10, 2023, View Source [SID1234635048]). These data were presented today during an oral presentation (OA05.05) at the 2023 World Conference on Lung Cancer (#WCLC23) hosted by the International Association for the Study of Lung Cancer.

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Ifinatamab deruxtecan is a specifically engineered potential first-in-class B7-H3 directed antibody drug conjugate (ADC) designed using Daiichi Sankyo’s (TSE: 4568) proprietary DXd ADC technology.

Lung cancer is the second most common cancer worldwide and SCLC represents about 15% of all cases.1,2 Approximately 65% of all SCLC tumors have a moderate-to-high expression of B7-H3, which is associated with disease progression and lower survival.2,3,4

A confirmed objective response rate (ORR) of 52.4% (95% CI: 29.8-74.3) was observed in 21 patients with advanced SCLC receiving ifinatamab deruxtecan (6.4 to 16.0 mg/kg) in the dose escalation part of the phase 1/2 trial. One complete response (CR) and 10 partial responses (PRs) were seen. A median duration of response (DOR) of 5.9 months (95% CI: 2.8-7.5) was observed. Median progression-free survival (PFS) was 5.6 months (95% CI: 3.9-8.1) and median overall survival (OS) was 12.2 months (95% CI: 6.4-NA) as of data cutoff of January 31, 2023.

Tumor reduction seen with ifinatamab deruxtecan was observed across a broad range of B7-H3 protein expression levels and no apparent trend of correlation between clinical efficacy parameters and B7-H3 protein expression was observed.

"With limited effective treatment options beyond traditional chemotherapy and immunotherapy, small cell lung cancer can be difficult to treat," said Melissa Johnson, MD, Director, Lung Cancer Research, Sarah Cannon Research Institute. "The high response rate, along with the fact that all patients except one experienced a reduction in tumor size with ifinatamab deruxtecan, is promising."

The safety profile of ifinatamab deruxtecan in patients with SCLC was consistent with previous reports in the overall population of this phase 1/2 trial. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 36.4% of patients. The most common (>20%) TEAEs occurring in patients were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%) and decreased appetite (22.7%). There was one grade 2 event confirmed to be treatment-related interstitial lung disease (ILD) or pneumonitis as determined by an independent adjudication committee. There was one grade 5 event of COVID-19 pneumonia that was determined not to be treatment related.

"In addition to the response rate seen with ifinatamab deruxtecan, we are further encouraged by the median overall survival seen in these patients at approximately one year," said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. "Additional evaluation of this B7-H3 directed antibody drug conjugate is underway in our ongoing phase 2 trial in patients with previously treated extensive-stage small cell lung cancer and we look forward to learning these results."

In the subset of patients with SCLC, two patients (9.1%) had brain metastases at baseline. Patients were heavily pretreated receiving a median of two prior lines of systemic therapy in the locally advanced/metastatic setting (range, 1-7), including platinum-based chemotherapy (100%), immunotherapy (81.8%), taxane chemotherapy (22.7%) and irinotecan or topotecan chemotherapy (22.7%). The median duration of follow up was 11.7 months (95% CI: 4.63-12.88) and two patients remain on treatment with ifinatamab deruxtecan.

Summary of SCLC Subset Analysis of Phase 1/2 Trial

Efficacy Measure

Patients with SCLC receiving doses of ifinatamab deruxtecan

(between 6.4 and 16.0 mg/kg)

n=21

Confirmed ORR, % (95% CI)

52.4% (29.8-74.3)
CR, n (%)

1 (4.8%)
PR, n (%)

10 (47.6%)
DOR, median (95% CI), months

5.9 months (2.8-7.5)
PFS, median (95% CI), months

5.6 months (3.9-8.1)
OS, median (95% CI), months

12.2 months (6.4-NA)
CR, complete response; DOR, duration of response; NA, not applicable; ORR, objective response rate; OS, overall survival; PR, partial response; PFS, progression-free survival.

About the Phase 1/2 Trial
The phase 1/2 trial is the first-in-human, open-label study evaluating the safety, tolerability and preliminary activity of ifinatamab deruxtecan in adult patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerable to standard treatment or for whom no standard treatment exists.

The phase 1 part of the trial (dose escalation) is assessing the safety and tolerability of increasing doses of ifinatamab deruxtecan to determine the maximum tolerated dose or recommended dose for expansion (RDE). This portion of the trial enrolled approximately 100 patients with advanced/unresectable or metastatic SCLC, squamous non-small cell lung cancer (NSCLC), metastatic castration-resistant prostate cancer (CRPC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma, bladder cancer, sarcoma, endometrial cancer, melanoma or breast cancer.

The phase 2 part of the trial (dose expansion) is evaluating the safety, tolerability and preliminary activity of ifinatamab deruxtecan in patients with squamous NSCLC, metastatic CRPC or ESCC.

The dose escalation part of the trial is evaluating dose-limiting toxicity and safety. The dose expansion part of the trial is evaluating ORR, DOR, disease control rate, PFS, OS and safety. Pharmacokinetic endpoints, exploratory biomarker and immunogenicity endpoints also will be assessed.

Patient enrollment in the ESCC and squamous NSCLC cohorts of the dose expansion part of the trial remains underway in Asia and North America. For more information, please visit ClinicalTrials.gov.

About Small Cell Lung Cancer
Lung cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide.1 The two main types of lung cancer include NSCLC, which represents more than 80 to 85% of all cases, and SCLC, which comprises about 15% of cases.2 The five-year survival rate is only 3% for patients diagnosed with advanced SCLC.5

About B7-H3
B7-H3 is a transmembrane protein that belongs to the B7 family, which also includes PD-L1.6 B7-H3 is overexpressed in a wide range of cancer types, including lung, prostate and esophageal, and its overexpression has been shown to correlate with poor prognosis in some cancers, making B7-H3 a promising therapeutic target.2,4,7,8,9,10 There are no B7-H3 directed medicines approved for the treatment of any cancer.

About Ifinatamab Deruxtecan
Ifinatamab deruxtecan (I-DXd) is an investigational potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Ifinatamab deruxtecan is being evaluated in a global development program, which includes IDeate-01, a phase 2 monotherapy trial in patients with previously treated extensive-stage SCLC, and a phase 1/2 first-in-human trial in collaboration with Sarah Cannon Research Institute.

About the DXd ADC Portfolio of Daiichi Sankyo
The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Four additional Daiichi Sankyo DXd ADCs include patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd; DS-7300), a B7-H3 directed ADC, raludotatug deruxtecan (R-DXd; DS-6000), a CDH6 directed ADC, and DS-3939, a TA-MUC1 directed ADC.

Designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.