On November 3, 2022 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported financial results and recent highlights for the third quarter ended September 30, 2022 (Press release, Cardiff Oncology, NOV 3, 2022, View Source [SID1234622976]).
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"We recently announced Phase 1b/2 data that demonstrate onvansertib’s ability to generate durable responses in KRAS-mutated mCRC patients, with various underlying mutations, when combined with standard-of-care FOLFIRI/bevacizumab. In addition, we observed an increase in objective response rate and progression-free survival in the bevacizumab-naïve subgroup of patients, providing key learnings to maximize ovansertib’s therapeutic and commercial potential," said Mark Erlander, PhD, chief executive officer of Cardiff Oncology. "In the fourth quarter we plan to activate ONSEMBLE, a randomized Phase 2 trial in our lead KRAS/NRAS-mutated mCRC program. This trial is designed to corroborate the robust signal of efficacy provided by the Phase 1b/2 results and position onvansertib for a possible accelerated approval opportunity by demonstrating its contribution over standard-of-care alone."
Dr. Erlander continued, "With a clear strategic focus and projected cash runway into 2025, we believe we are well positioned to generate value from each of our programs in the coming months and years."
Recent highlights for the quarter ended September 30, 2022 include:
KRAS/NRAS-mutated mCRC Program:
ONSEMBLE, a Phase 2, open-label, randomized trial for second line treatment of KRAS/NRAS-mutated mCRC, on track for activation in Q4 2022
The Company designed the ONSEMBLE trial to corroborate the robust efficacy signal observed in the Phase 1b/2 trial of onvansertib plus standard-of-care (SoC) FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC, demonstrate onvansertib’s contribution above SoC alone and confirm the optimal dose. ONSEMBLE is expected to enroll approximately 150 patients who will be randomized 1:1:1 to receive SoC alone, SoC plus 20 mg onvansertib, or SoC plus 30 mg onvansertib, with onvansertib administered on days 1-5 and 15-19 of 28-day treatment cycles. The primary endpoint of the trial is objective response rate (ORR). Progression-free survival (PFS) and duration of response (DoR) will be key secondary endpoints. Activation of the trial is expected in Q4 2022, and topline data are expected in 2H 2024.
Phase 1b/2 mCRC data show durable response to treatment across multiple KRAS-mutation variants, as well as an objective response rate and median progression-free survival that substantially exceed those observed in historical control trials
Data from the Phase 1b/2 trial of onvansertib plus FOLFIRI/bevacizumab in second line KRAS-mutated mCRC were presented during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 and on a company webcast on September 12, 2022. Key data and conclusions featured in these presentations include:
•Objective response rate (ORR) across all evaluable patients was 35% (n=48) as compared to an ORR of 5-13% observed historically1-4, and the median duration of response (mDoR) across all evaluable patients was 11.7 months
•Median progression-free survival (mPFS) was 9.3 months across all evaluable patients, as compared to mPFS of ~4.5 – 5.7 months observed historically in combination trials that included the standard-of-care FOLFIRI with bevacizumab1-4
Subgroup analysis from Phase 1b/2 mCRC trial shows improved ORR and mPFS in bevacizumab naïve patients
A recently reported subgroup analysis from the ongoing Phase 1b/2 clinical trial of onvansertib plus FOLFIRI/bevacizumab in second line KRAS-mutated mCRC showed an ORR of 69% and mPFS of 13.5 months in bevacizumab naïve patients (n=13). These data compare favorably to historical control trials in mCRC, which show an ORR of approximately 25% and a mPFS of approximately 6.9 months in bevacizumab naïve patients4-9. The observed increase in ORR in bevacizumab naïve patients in the Phase 1b/2 trial was seen consistently across all patient characteristics and demographics. Based on these findings, the Company plans to stratify for prior bevacizumab exposure within the randomization of the ONSEMBLE trial and conduct preclinical studies to explore the apparent synergy between onvansertib and bevacizumab.
Data presented at the ESMO (Free ESMO Whitepaper) conference suggest combining onvansertib with irinotecan (a component of FOLFIRI) overcomes irinotecan-resistance in RAS-mutated mCRC
Findings from Cardiff Oncology’s Expanded Access Program (EAP) of onvansertib in KRAS-mutated mCRC as well as preclinical data from patient-derived xenograft (PDX) models of irinotecan-resistant, RAS-mutated mCRC were featured in a poster at the ESMO (Free ESMO Whitepaper) Congress 2022. Highlights from the presentation include:
•EAP patients with prior irinotecan treatment (43 of 51) showed clinical benefit following treatment
•The combination of onvansertib and irinotecan showed significantly greater anti-tumor activity compared to onvansertib monotherapy in 5 of 6 tested PDX models of irinotecan-resistant, RAS-mutated CRC
Collectively, these results support the observed mDoR in Cardiff Oncology’s ongoing Phase 1b/2 trial in KRAS-mutated mCRC and suggest onvansertib may combine with irinotecan to overcome mechanisms driving intrinsic and refractory resistance.
Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) Program:
Preliminary data provide early signal of efficacy and compare favorably to historical control trials
Preliminary data from five evaluable patients in an ongoing open-label Phase 2 trial of onvansertib in combination with nanoliposomal irinotecan and 5-FU in second-line metastatic PDAC showed one patient achieving an initial partial response (PR) and three patients achieving stable disease (SD). Based on prior clinical studies, the historical ORR and mPFS for second-line mPDAC patients are 7.7% and 3.1 months, respectively10,11. All four patients achieving a PR or SD remained on study without disease progression as of the data cut-off date and all have shown tumor shrinkage from baseline. Additional data from the ongoing Phase 2 trial are expected in mid-2023.
Investigator-initiated Trials
Trials in triple negative breast cancer (TNBC) and small cell lung cancer (SCLC) enrolled first patients
A single-arm, Phase 1b/2 trial of onvansertib in combination with paclitaxel in patients with unresectable locally advanced or metastatic TNBC recently enrolled its first patient at Dana Farber Cancer Institute (DFCI). Preliminary data from the trial are expected in late 2023 or early 2024. For more information, please visit NCT05383196.
A single-arm, two-stage, Phase 2 trial of onvansertib monotherapy in patients with relapsed SCLC recently enrolled its first patient at the University of Pittsburgh Medical Center (UPMC). Preliminary data from the trial are expected in mid-2023. For more information, please visit NCT05450965.
Third Quarter 2022 Financial Results:
Liquidity, cash burn and cash runway
As of September 30, 2022, Cardiff Oncology had approximately $114 million in cash, cash equivalents, and short-term investments.
Net cash used in operating activities for the third quarter of 2022 was approximately $7.5 million, an increase of approximately $2.0 million from $5.5 million for the same period in 2021. Based on its current expectations and projections, the Company believes its current cash resources are sufficient to fund its operations into 2025.
Operating Expenses
The overall increase in research and development expenses was primarily related to chemistry, manufacturing, and controls ("CMC"); and clinical pharmacology studies to support the development of our lead drug candidate, onvansertib. Salaries and staff costs increased primarily due to additional hires in senior management and our clinical operations team.
The overall increase in selling, general and administrative expense was primarily due to higher salaries costs from merit increases and additional new hires. An increase in D&O insurance costs also contributed to higher selling, general and administrative expenses in the current period, offset by a reduction in recruiting fees from the prior period.