On June 4, 2021 Cullinan Oncology, Inc. (Nasdaq: CGEM) ("Cullinan"), an oncology company seeking to drive shareholder returns by focusing on the patient, reported additional details pertaining to Cullinan Pearl’s ongoing Phase 1/2a trial of CLN-081 in Non-Small Cell Lung Cancer (NSCLC) patients whose tumors harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations (Press release, Cullinan Oncology, JUN 4, 2021, View Source [SID1234583537]). CLN-081 is an orally available, irreversible EGFR inhibitor, utilizing a unique pyrrolopyrimidine scaffold that was designed to selectively target cells expressing mutant EGFR variants, including exon 20, while sparing cells expressing wild type (WT) EGFR.

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These data will be featured in an on-demand poster presentation available this morning at 9:00 am EDT at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and during a company sponsored webinar at 10:30 am EDT today, which can be accessed here or in the ‘Events’ section on Cullinan’s investor website.

"We remain encouraged with CLN-081’s emerging profile," stated Owen Hughes, Cullinan’s Chief Executive Officer. "In heavily pretreated patients, CLN-081 continues to show antitumor activity across the dose range, with a safety profile that appears to be differentiated, most specifically with respect to GI adverse events."

The current analysis of the ongoing trial evaluated a total of 45 NSCLC patients with EGFR exon 20 insertion mutations who received at least one dose of CLN-081 as of the April 1, 2021, data cutoff, and were evaluable for safety. CLN-081 was dosed orally, at dose levels including 30, 45, 65, 100 and 150 mg twice daily (BID). As of the data cutoff, 42 of 45 patients were response evaluable across all dose cohorts tested.

Overall Safety:

Regarding treatment related adverse events (TRAEs) associated with WT EGFR inhibition:

Rash has been limited to Grade 1 and 2 events (76% of patients experienced an event across all doses as of the data cutoff); events were manageable with conventional supportive care; no patients have experienced Grade ≥3 TRAE rash.

Similarly, diarrhea has been mostly limited to Grade 1 and 2 events (22% across the dose range) as of the data cutoff, with a single Grade ≥3 TRAE at the highest dose tested to date, 150 mg BID, which resolved with supportive care. No prophylactic regimen has been required to ameliorate the incidence or severity of diarrhea to date.
Overall Efficacy:

Objective partial responses (PR) were observed in 21 of 42 (50%) response evaluable patients treated across all dose levels.

Of the 21 PRs as of the data cutoff, 13 were confirmed (31% confirmed objective response rate), 5 were pending confirmation (i.e., patient had not reached their second post-baseline disease assessment as of the data cutoff), and 3 will remain unconfirmed.

41 of 42 (98%) response evaluable patients have achieved a best response of stable disease (SD) or PR, with 76% of all patients showing some degree of tumor regression at the initial scan post baseline (week 6).
100 mg BID Expansion Cohort:

In February 2021, Cullinan announced a Phase 2a expansion at the 100mg BID cohort, allowing enrollment of up to 36 patients.

Safety: Treatment-related rash has been limited to Grade 1 and 2 events (66%), manageable with conventional supportive care; no patients have experienced Grade ≥3 TRAE rash. In addition, the overall incidence of treatment-related diarrhea was 26%, with no Grade ≥3 events to date.

Efficacy: As of the data cutoff, objective responses were observed in 7 of 13 (54%) response evaluable patients; 6 of which were confirmed (46%) and 1 will remain unconfirmed.

Of the 13 response evaluable patients, 9 (69%) patients achieved disease control (PR of any duration or SD ≥ 6 months) as of the data cutoff; an additional 3 patients had stable disease and remained on treatment but had started therapy less than 6 months prior to data cutoff.
"We are pleased with the CLN-081 safety and efficacy data to date in our Phase 1/2a trial. CLN-081 has demonstrated antitumor activity in patients post systemic chemotherapy, including among patients who were also treated previously with other EGFR inhibitors and/or cancer immunotherapy, across the range of CLN-081 doses tested to date, and across a spectrum of exon-20 mutational sub-types," said Jon Wigginton, M.D., Chairman of the Cullinan Oncology Scientific Advisory Board and Senior Advisor. "We are working diligently to evaluate CLN-081 in additional patients, and to set the stage for further clinical advancement of CLN-081 in this group of patients with significant unmet need."

About CLN-081

CLN-081 is an orally available, irreversible EGFR inhibitor that was designed to selectively target cells expressing mutant EGFR variants, including Ins20, while sparing cells expressing wild type EGFR. In preclinical studies, CLN-081 demonstrated inhibition against traditional sensitizing mutations (exon 19 deletions and L858R), Ins20 (the third most common EGFR mutation), and other less common mutations (G719X, L861Q, and S768I).

Cullinan is evaluating various doses of CLN-081 in a Phase 1/2a trial in patients with NSCLC harboring Ins20 mutations that have progressed post chemotherapy. Based on pre-specified efficacy and safety criteria, Cullinan recently initiated Phase 2a dose expansion in the 100 mg BID dosing cohort, which will enable enrollment of up to 36 patients at this dose level, inclusive of 13 previously enrolled patients.