1641P - ABCG transporter and SRPK1 kinase inhibition of chemotherapy resistance: A phase Ib clinical trial of safety and maximum tolerated dose for SCO-101 in combination with gemcitabine and nab-paclitaxel in inoperable pancreatic cancer

Background

Gemcitabine (Gem) and nab-paclitaxel (Nab) is a standard treatment for pts with inoperable pancreatic cancer (iPC), but a high frequency of chemoresistance is observed clinically. SCO-101 is a compound for oral use that was shown to revert drug resistance in preclinical studies: In taxane-resistant cancer cells SCO-101 resensitized tumor cells to taxane and reduced the active efflux of ATP Binding Cassette G2 substrate molecules from irinotecan resistant colon cancer cells. Moreover, SCO-101 inhibits Serinine-Arginine Protein Kinase 1, which may increase sensitivity of tumor cells to Gem. In clinical phase I studies, SCO-101 was well tolerated after single (up to 200 mg) and multiple (up to 150 mg daily for 14 days) doses.

Methods

This open-label, phase Ib study was conducted at four centers in Denmark and Germany as a standard 3+3 dose escalation study with increasing doses of SCO-101 and 80% dose of Gem-Nab in pts with iPC. Here we report on the primary objective to determine safety and Maximum Tolerated Dose (MTD) by evaluation of Dose-Limiting Toxicities (DLTs) related to SCO-101 during the first treatment cycle.

Results

22 pts were included. Median age was 65 years (range 51-77) and 16 had ECOG PS=0. 11 pts had prior PC-related surgery and 19 had previously received chemotherapy. SCO-101 was dosed once daily for 6 days on days 1-6 and 15-20 on a bi-weekly schedule and chemotherapy given on day 6, 13 and 20. MTD was determined to be 200mg (Table). DLTs included increased conjugated bilirubin and decreased platelet count.

Table: 1641P

Results of dose escalation

Conclusions

The combination of SCO-101 and Gem-Nab was generally well tolerated. DLTs were observed in 2 pts in the cohort treated with 250mg of SCO-101, hence MTD for SCO-101 concurrent with Gem-Nab was determined to be 200mg once daily for 6 days on a bi-weekly schedule. A full description of toxicities is pending.

Clinical trial identification

NCT04652206.

Editorial acknowledgement

The authors M.L and S.S contributed equally.

Legal entity responsible for the study

Region Nordjylland.

Funding

Scandion Oncology A/S.

Disclosure

M. Ladekarl: Financial Interests, Institutional, Research Grant: Scandion Oncology A/A. A. Reinacher-Schick: Financial Interests, Personal, Invited Speaker: Amgen, Roche, Merck, Bristol Myers Squibb, MSD, MCI Group, AstraZeneca; Financial Interests, Personal, Advisory Board: Amgen, Roche, Merck, Bristol Myers Squibb, AstraZeneca, Pierre Fabre; Financial Interests, Personal, Other, Travel support: Roche, Amgen, Pierre Fabre; Financial Interests, Institutional, Research Funding: Roche, Ipsen, Roche, Celgene, Ipsen, Amgen, Alexion Pharmaceuticals, AstraZeneca, Lilly, Servier, AIO Studien GmbH, Rafael Pharmaceutics, Erytech Pharma, BioNTech. J. Stenvang: Financial Interests, Personal, Stocks/Shares: Scandion Oncology A/S; Financial Interests, Personal, Full or part-time Employment: Scandion Oncology A/S; Financial Interests, Personal, Other, Co-founder: Scandion Oncology A/S. A. Zurlo: Financial Interests, Personal, Full or part-time Employment: Scandion Oncology A/S. N. Lindland Roest: Financial Interests, Personal, Full or part-time Employment: Scandion Oncology A/S. All other authors have declared no conflicts of interest.