Cardiff Oncology Announces Positive Update from its Randomized Phase 2 Trial of Onvansertib in First-line RAS-mutated mCRC

Rhea-AI Summary

Cardiff Oncology (NASDAQ: CRDF) reported positive Phase 2 CRDF-004 results for onvansertib in first-line RAS-mutated metastatic colorectal cancer (mCRC). In an intent-to-treat analysis (data cut Jan 22, 2026) the 30 mg onvansertib + FOLFIRI/bevacizumab arm showed a confirmed objective response rate of 72.2% versus 43.2% for pooled standard of care, and a PFS hazard ratio 0.37 vs SoC (p=0.048) with median PFS not reached versus 10.97 months for SoC. Safety was manageable with no major additive toxicity. The company selected the 30 mg dose for a planned registrational program and expects final data and registrational plans in H1 2026.

Positive

• Confirmed ORR 72.2% for onvansertib 30 mg + FOLFIRI/bev
• PFS HR 0.37 versus SoC with p=0.048
• Median PFS not reached for 30 mg arm versus 10.97 months SoC
• 30 mg dose selected for planned registrational program
• Treatment well-tolerated with no major additive toxicity reported

Negative

• ORR p-value = 0.051 (did not meet conventional 0.05 significance)
• Small arm sizes (n=18 for each onvansertib dose) limit statistical power
• PFS confidence interval upper bound marginally >1 (uncertain robustness)

Market Reaction

-32.69% $1.98 6.8x vol

15m delay 16 alerts

-32.69% Since News

-1.9% Trough in 0 min

$1.98 Last Price

$1.85 $2.10 Day Range

-$65M Valuation Impact

$133M Market Cap

6.8x Rel. Volume

Following this news, CRDF has declined 32.69%, reflecting a significant negative market reaction. Argus tracked a trough of -1.9% from its starting point during tracking. Our momentum scanner has triggered 16 alerts so far, indicating notable trading interest and price volatility. The stock is currently trading at $1.98. This price movement has removed approximately $65M from the company's valuation. Trading volume is exceptionally heavy at 6.8x the average, suggesting significant selling pressure.

Data tracked by StockTitan Argus (15 min delayed). Upgrade to Silver for real-time data.

Key Figures

ORR 30 mg arm: 72.2% ORR SoC: 43.2% Median PFS SoC: 10.97 months +5 more

8 metrics

ORR 30 mg arm 72.2% Confirmed objective response rate vs SoC in CRDF-004 ITT population

ORR SoC 43.2% Confirmed objective response rate in combined SoC arms (n=37)

Median PFS SoC 10.97 months Median progression-free survival (95% CI 9.43–15.44)

6-mo PFS rate 30 mg 94.1% PFS rate at 6 months (95% CI 83.6–100) for onvansertib 30 mg

6-mo PFS rate SoC 88.8% PFS rate at 6 months (95% CI 77.4–100) in SoC arms

PFS HR vs SoC 0.37 Hazard ratio for PFS, onvansertib 30 mg vs SoC (p=0.048)

Trial size SoC 37 patients Number of patients in combined SoC arms in CRDF-004

Trial ID NCT06106308 CRDF-004 Phase 2 trial identifier on clinicaltrials.gov

Market Reality Check

Price: $2.94 Vol: Volume 614,575 is 0.76x t...

normal vol

$2.94 Last Close

Volume Volume 614,575 is 0.76x the 20-day average of 804,050, suggesting no pre-news rush into the stock. normal

Technical Shares at $2.94 are trading above the 200-day MA of $2.72, but still 41.08% below the 52-week high.

Peers on Argus

CRDF gained 1.38% while peers showed mixed moves: ACTU, GNLX, SKYE up, AVTX and ...

CRDF gained 1.38% while peers showed mixed moves: ACTU, GNLX, SKYE up, AVTX and ONCY down, indicating a stock-specific reaction rather than a coordinated biotech move.

Previous Clinical trial Reports

5 past events · Latest: Dec 08 (Positive)

Same Type Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Dec 08	CMML Phase 1 data	Positive	+10.9%	Phase 1 CMML data showed ~40% preliminary efficacy and good tolerability.
Jul 29	mCRC Phase 2 update	Positive	-24.8%	Positive CRDF-004 data with 49% ORR in 30mg arm vs 30% control.
Apr 15	CRDF-004 enrollment	Neutral	-4.4%	Completion of Phase 2 CRDF-004 enrollment and trial design details.
Dec 10	Initial CRDF-004 data	Positive	+54.9%	Initial Phase 2 data with 64% ORR in 30mg arm vs 33% control.
Oct 30	JCO publication	Positive	+0.0%	JCO publication of second-line mCRC Phase 2 data with strong bev-naïve results.

Pattern Detected

Clinical trial updates have triggered wide swings, from -24.77% to +54.92%, with both sharp rallies and selloffs on positive data.

Recent Company History

Over the past 15 months, Cardiff Oncology has repeatedly reported clinical progress with onvansertib across mCRC and CMML. Early CRDF-004 data in Dec 2024 and subsequent Phase 2 updates in Apr and Jul 2025 showed dose-dependent efficacy and favorable safety, yet market reactions ranged from a 54.92% spike to a -24.77% drop. A CMML Phase 1 poster in Dec 2025 also produced a double-digit gain. Today’s randomized Phase 2 update extends this sequence of efficacy-focused announcements in first-line RAS-mutated mCRC.

Historical Comparison

clinical trial

+19.0 %

Average Historical Move

Historical Analysis

Clinical-trial headlines for CRDF have averaged a 19% move. Against that backdrop, today’s modest 1.38% gain looks restrained versus past reactions to onvansertib data.

Typical Pattern

Clinical updates trace a path from initial CRDF-004 data in 2024, through full enrollment and multiple interim reads in 2025, to the current randomized Phase 2 results supporting a registrational program.

Market Pulse Summary

The stock is dropping -32.7% following this news. A negative reaction despite today’s positive rando...

Analysis

The stock is dropping -32.7% following this news. A negative reaction despite today’s positive randomized Phase 2 update would fit the pattern seen on Jul 29, 2025, when favorable CRDF-004 data coincided with a -24.77% move. History shows that clinical wins have not always translated into sustained strength, as the market has also focused on trial risk, timelines, and capital requirements. Such a decline would not, by itself, negate the reported efficacy and safety profile.

Key Terms

progression-free survival, objective response rate, hazard ratio, metastatic colorectal cancer, +4 more

8 terms

progression-free survival medical

"dose-dependent improvement in overall response rates and durability trends as measured by progression-free survival"

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

objective response rate medical

"Objective Response Rate (per BICR) a"

The objective response rate (ORR) is the percentage of patients in a clinical trial whose tumors measurably shrink or disappear according to preset rules. Investors use it as a quick, objective signal of a drug’s ability to produce a clear treatment effect—like counting how many plants visibly respond after applying a new fertilizer—and higher ORR can improve odds of regulatory approval, commercial success, and company valuation.

hazard ratio medical

"PFS HR (vs SoC)"

A hazard ratio is a way scientists compare the chance of something happening over time between two groups, like patients taking different medicines. If the ratio is high, it means one group is more likely to experience the event sooner or more often, which helps determine how effective a treatment is or how risky a situation might be.

metastatic colorectal cancer medical

"first-line (1L) RAS-mutated metastatic colorectal cancer (mCRC)"

Metastatic colorectal cancer is cancer that started in the colon or rectum and has spread to other parts of the body, most often the liver or lungs, making it harder to treat. For investors, it matters because advanced disease drives demand for more intensive treatments, ongoing clinical trials, and long-term care costs; think of it like a fire that has jumped from one room to multiple rooms, requiring bigger, more expensive responses and creating larger market opportunities and regulatory scrutiny.

bevacizumab medical

"FOLFIRI/bevacizumab (bev) or FOLFOX/bev"

A targeted cancer and eye‑disease drug that works by blocking a protein tumors and abnormal eye tissue use to grow new blood vessels, effectively 'cutting off the supply lines' they need to expand. Investors watch it because sales, patent status, regulatory approvals, and competing copies (biosimilars) can drive significant revenue shifts, affect treatment standards, and influence the maker’s stock and competing firms’ market prospects.

blinded independent central review medical

"Objective Response Rate (per BICR) a"

Blinded independent central review is a quality-control step in clinical trials where outside medical experts, who do not know which patients received the experimental therapy, re-examine key measurements (like scans or lab results) to prevent bias. Think of it as neutral referees watching game footage without knowing the teams, which gives investors greater confidence that the trial results are fair, more reliable for regulators, and less likely to be overturned or disputed.

treatment-emergent adverse event medical

"neutropenia being the most common treatment-emergent adverse event"

An event is called a treatment-emergent adverse event when a new or worsening unwanted health effect appears after a person starts a drug or medical treatment, typically measured from the first dose onward in clinical studies. Investors watch these events because they can stop or slow product approval, raise development costs, or undermine market confidence—like a widely reported defect in a new gadget that triggers recalls and damages sales.

Phase 3 trial medical

"encouraging enough to test in a large Phase 3 trial"

A Phase 3 trial is a large, late-stage test of a new drug or medical treatment done on many people to make sure it really works and is safe. For investors, it matters because a successful Phase 3 usually means the company can ask regulators to sell the product and could earn lots of money, while failure can sharply reduce the company’s value.

AI-generated analysis. Not financial advice.

- Onvansertib added to FOLFIRI/bev first-line standard of care regimen showed dose-dependent improvement in overall response rates and durability trends as measured by progression-free survival in patients with RAS-mutated mCRC –

- Data support selection of 30 mg onvansertib dose for registrational program in first-line RAS-mutated mCRC –

- Data validate previously reported positive results from Phase 2 trial of onvansertib with FOLFIRI/bev in second-line mCRC bev-naïve patients, as published in the Journal of Clinical Oncology –

- Onvansertib continues to be safe and well-tolerated –

- Company expects to provide final data and registrational plans in first half of 2026 –

- Company to hold conference call today at 8:30 a.m. ET/5:30 a.m. PT -

SAN DIEGO, Jan. 27, 2026 (GLOBE NEWSWIRE) -- Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, today announced a positive update from CRDF-004, a randomized dose-finding Phase 2 clinical trial evaluating onvansertib in combination with standard of care (SoC) regimens (FOLFIRI/bevacizumab (bev) or FOLFOX/bev) in patients with first-line (1L) RAS-mutated metastatic colorectal cancer (mCRC). In an intent-to-treat analysis, the clinical data show dose-dependent benefits across multiple efficacy measures in patients receiving onvansertib with FOLFIRI/bev compared to patients receiving either SoC regimen. In this trial, onvansertib with FOLFIRI/bev also performed better than onvansertib with FOLFOX/bev.

Based on these results, the Company has selected the 30 mg dose of onvansertib with FOLFIRI/bev to bring forward in a registrational trial in 1L patients with RAS-mutated mCRC. Cardiff Oncology plans to initiate a registrational program later this year pending finalization of the trial design in consultation with the FDA, in which the Company expects to compare onvansertib with FOLFIRI/bev to SoC regimens, FOLFIRI/bev or FOLFOX/bev.

“These data demonstrate promising enhanced benefits of onvansertib when combined with FOLFIRI/bev in RAS-mutated mCRC patients,” said Mani Mohindru, PhD, interim Chief Executive Officer. “We observed a consistent, dose-dependent treatment benefit across multiple measures of efficacy, including achieving statistical significance for PFS compared to SoC even with relatively small patient numbers. The 30 mg onvansertib–FOLFIRI/bev arm outperformed both SoC arms with no significant additive toxicity, supporting findings from our previous Phase 2 trial in second-line RAS-mutated mCRC. While we continue to review data from the ongoing trial, our plan is to rapidly move forward with the onvansertib 30 mg dose in combination with FOLFIRI/bev and we believe confirmatory data from a registrational trial has the potential to make this regimen a new SoC for 1L treatment of RAS-mutated mCRC.”

Topline Results in intent-to-treat (ITT) population, data cut-off as of January 22, 2026

Parameter	SoCc (FOLFIRI/bev+FOLFOX/bev) (n=37)		FOLFIRI/bev (n=19)	Onv 20 mg +FOLFIRI/bev (n=18)	Onv 30 mg +FOLFIRI/bev (n=18)
Objective Response Rate (per BICR)a
Confirmed Responders	16		8	8	13
Confirmed ORR (%)	43.2		42.1	44.4	72.2 p-value = 0.051f (vs SoC)
Progression Free Survivalb
Median PFS (months, 95% CI)	10.97 (9.43-15.44)		10.97 (7.52-NR)	NR (7.49-NR)	NR (9.72-NR)
PFS HR (vs FOLFIRI/bev)				0.56 (0.18-1.73)d	0.38 (0.12-1.17)d
PFS HR (vs SoC)				0.57 (0.21-1.58)e	0.37 (0.13-1.02)e p-value = 0.048g (vs SoC)
PFS Rate at 6 months (95% CI)	88.8 (77.4-100)		79.5 (61.1-100)	88.1 (73.9-100)	94.1 (83.6-100)

Bev=bevacizumab; BICR=Blinded Independent Central Review; CI=confidence interval; HR=hazard ratio; NR=not reached; Onv=onvansertib; ORR=objective response rate; PFS=progression-free survival; SoC=standard of care.
^aORR is confirmed responses
^bProgressive disease events were based on combined BICR and Investigator assessments due to very small number of events in BICR assessment. The earliest reported date was used for a conservative estimate.
^cSoC is the combination of the FOLFIRI/bev and FOLFOX/bev arms
^dPFS HR is the comparison of the onvansertib arm to FOLFIRI/bev
^ePFS HR is the comparison of the onvansertib arm to SoC
^fFisher’s exact test
^gLog-rank test

“There is a clear need for improved first-line treatment options for patients with mCRC, especially the half of those with RAS-mutated disease,” said Dr. J Randolph Hecht, MD, Professor of Clinical Medicine at the David Geffen School of Medicine at UCLA. “Unfortunately, first-line treatment for these patients hasn’t improved significantly for more than two decades. Onvansertib has a novel mechanism of action and these preliminary responses and PFS results in combination with FOLFIRI/bevacizumab are encouraging enough to test in a large Phase 3 trial. If such a trial were positive, it could become a new standard of care for these patients.”

Onvansertib in combination with both chemo/bev regimens was well-tolerated. There were no major or unexpected toxicities observed and no additive adverse events. Grade 3 or higher adverse events were infrequent, with neutropenia being the most common treatment-emergent adverse event across both the onvansertib combination and standard of care arms.

Conference Call and Webcast
Cardiff Oncology will host a conference call and live webcast today, January 27, 2026 at 8:30 a.m. ET / 5:30 a.m. PT. Individuals interested in listening may do so by using the link in the "Events" section of the Company's website. A replay will be available in the investor relations section on the Company's website following the completion of the call.

CRDF-004 Trial Design
The CRDF-004 Phase 2 trial was designed to evaluate two doses of onvansertib to identify the lowest maximally effective dose and to assess the safety, efficacy, and pharmacokinetics of onvansertib in combination with FOLFIRI/bevacizumab or FOLFOX/bevacizumab in first-line patients with KRAS- or NRAS-mutated metastatic colorectal cancer (mCRC). The trial’s endpoints include objective response rate (ORR), progression-free survival (PFS), duration of response, and safety.

For additional information about the trial, please visit www.clinicaltrials.gov (Trial ID: NCT06106308).

About Onvansertib
Onvansertib is a highly specific, oral PLK1 inhibitor currently in mid-stage clinical development for RAS-mutated metastatic colorectal cancer. It is also being evaluated in multiple other cancers through investigator-initiated studies, including metastatic pancreatic ductal adenocarcinoma (mPDAC), small cell lung cancer (SCLC), triple-negative breast cancer (TNBC), and chronic myelomonocytic leukemia (CMML). Promising monotherapy clinical results from an ongoing CMML trial were recently presented at the American Society of Hematology annual meeting in December 2025. CMML represents a rare disease with significant unmet need.

About Cardiff Oncology, Inc.
Cardiff Oncology is a clinical-stage biotechnology company advancing innovative cancer treatments focused on PLK1 inhibition, a validated oncology target with practice-changing potential. Our lead asset, onvansertib, is a highly specific, oral PLK1 inhibitor currently being evaluated in a Phase 2 trial for first-line treatment of RAS-mutated metastatic colorectal cancer (mCRC), addressing a large, underserved patient population with high unmet need. Onvansertib is also under investigation in other PLK1-driven cancers through ongoing investigator-initiated trials and has shown robust single agent clinical activity in hard-to-treat tumors. By targeting tumor vulnerabilities, we aim to overcome treatment resistance and deliver improved clinical outcomes for patients.

For more information, please visit https://www.cardiffoncology.com.

Forward-Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified using words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Cardiff Oncology's expectations, strategy, plans or intentions. These forward-looking statements are based on Cardiff Oncology's current expectations and actual results could differ materially. There are several factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidate; results of preclinical studies or clinical trials for our product candidate could be unfavorable or delayed; our need for additional financing; risks related to business interruptions, including the outbreak of COVID-19 coronavirus and cyber-attacks on our information technology infrastructure, which could seriously harm our financial condition and increase our costs and expenses; uncertainties of government or third party payer reimbursement; dependence on key personnel; limited experience in marketing and sales; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. There are no guarantees that our product candidate will be utilized or prove to be commercially successful. Additionally, there are no guarantees that future clinical trials will be completed or successful or that our product candidate will receive regulatory approval for any indication or prove to be commercially successful. Investors should read the risk factors set forth in Cardiff Oncology's Form 10-K for the year ended December 31, 2024, and other periodic reports filed with the Securities and Exchange Commission. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Forward-looking statements included herein are made as of the date hereof, and Cardiff Oncology does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.

Investor Contact:
Candice Masse
Astr Partners
candice.masse@astrpartners.com

Media Contact:
Amy Bonanno
Lyra Strategic Advisory
abonanno@lyraadvisory.com

FAQ

What were the key CRDF-004 Phase 2 results for CRDF on Jan 27, 2026?

The 30 mg onvansertib + FOLFIRI/bev arm showed ORR 72.2% and PFS HR 0.37 vs SoC (p=0.048) with median PFS not reached (data cut Jan 22, 2026).

Why did Cardiff Oncology (CRDF) choose the 30 mg onvansertib dose?

The company selected 30 mg because the 30 mg + FOLFIRI/bev arm showed the strongest dose-dependent efficacy and acceptable safety in CRDF-004.

What is the planned next step for onvansertib in RAS-mutated mCRC (CRDF)?

Cardiff plans a registrational program comparing onvansertib 30 mg + FOLFIRI/bev to standard regimens, with trial design finalization with the FDA and initiation expected later in 2026.

How significant are the efficacy signals for CRDF-004 given the trial size?

Efficacy signals include a p=0.048 for PFS versus SoC, but small arm sizes (n=18) and borderline statistics (e.g., ORR p=0.051) warrant confirmatory Phase 3 data.

What safety findings did Cardiff report for onvansertib in CRDF-004?

Onvansertib combinations were reported as well-tolerated with no major unexpected toxicities and grade ≥3 events infrequent; neutropenia was the most common treatment-emergent AE.