Operator
Welcome to the Cardiff Oncology Clinical Development Update Conference Call. [Operator Instructions] As a reminder, this call is being recorded today, Tuesday, September 26, 2023.
I would now like to turn the conference over to Kiki Patel of Gilmartin Group. Please go ahead.
Kiki Patel
Thank you, operator. Slides for today's investor call can be found on the home page and the Events and Presentation tab of the Cardiff Oncology website www cardiffoncology.com. Joining us on the call today from Cardiff Oncology are Chief Executive Officer, Mark Erlander; and Chief Medical Officer, Dr. Fairooz Kabbinavar.
During this call, management will make forward-looking statements, including without limitation statements related to guidance, results and the timing of data readouts for onvansertib clinical. These forward-looking statements are based on the company's current expectations and inherently involve significant risks and uncertainties. Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties.
Factors that could cause results to be different from these statements include factors the company describes in the section titled Risk Factors in our annual report on Form 10-K for the year ended December 31, 2022, filed with the SEC on March 2, 2023. Cardiff Oncology undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events or changes in its expectations.
With that, I turn the call over to Chief Executive Officer, Mark Erlander.
Mark Erlander
Well, thank you, Kiki, and good afternoon, everyone. We are pleased that you've joined us today for this clinical development update. As you know, on August 7, we provided a comprehensive look at our lead program in first-line RAS-mutated metastatic colorectal cancer or mCRC. And today, we are providing an update on 2 earlier-stage programs as they compare to CRC: in metastatic pancreatic ductal adenocarcinoma, which we will refer to as metastatic PDAC; and extensive-stage relapsed small cell lung cancer.
I would like to start on Slide 3 by highlighting -- providing the highlights of the important data that we will be announcing today. For PDAC, we will be discussing 3 separate clinical trials. For the first trial, CRDF-001, we will be providing an update to the data we released last September, showing efficacy and tolerability in second-line PDAC setting for the combination of onvansertib with standard of care.
The second PDAC trial is a biomarker discovery trial that we have never discussed publicly before. This trial examines how a 10-day course of onvansertib monotherapy impacted well-known and validated response biomarkers. This trial was not designed to treat patients for traditional measures of efficacy response. As you will see, 1 of the 2 patients we have treated so far had a significant biomarker response or FOLFIRI Index and CA-199.
And additionally, we are excited to see that extensive genomic transcriptome analysis for this response of patient showed that at baseline a high hypoxia-related signal, which was inhibited after 10 days of onvansertib monotherapy. These results are exciting because they are consistent with our preclinical colorectal cancer finding.
Finally, we will provide clarity on our path forward, which consists of the third PDAC trial, which we will discuss today. Based on the totality of the clinical and preclinical data, our plan is to shift onvansertib's development in metastatic PDAC to the first-line setting through a new investigator-initiated trial.
Next is the exciting data from the onvansertib monotherapy investigator-initiated trial in relapsed extensive-stage small cell lung cancer. Here, we are able to report today a confirmed partial response within the first 7 patients. This is a very significant milestone because it demonstrates single-agent activity or onvansertib in a very challenging indication.
On Slide 4, before we get into the new clinical data, I would like to briefly review the important attributes of our drug, onvansertib, that we believe will enable us to become the first-in-class well-tolerated PLK1 inhibitor. Onvansertib is a small molecule, oral and has a 24-hour half-life, allowing for flexible dosing schedules. Together with onvansertib's high specificity for PLK1 versus PLK2 and 3, we believe that these factors explain why we have observed in over 300 patients across 4 different clinical trials that onvansertib is well tolerated even when combined with a variety of chemotherapies.
On Slide 5, we show our development pipeline. During our last company call on August 7, as you know, we announced a first-line clinical development path for a lead program in RAS-mutated metastatic CRC. One of the additions to our pipeline that you can see on this slide is a new investigator-initiated trial in first-line metastatic PDAC planned at the Oregon Health & Science University Knight Cancer Institute.
In a moment, our Chief Medical Officer, Dr. Kabbinavar, will provide the rationale for this move. Similar to our shift in -- to first line in metastatic CRC, our development strategy follows our data, both clinical and preclinical, to enable onvansertib to benefit the largest possible patient populations. These investigator-initiated trials are a highly capital-efficient way to evaluate onvansertib in new indications.
On Slide 6, we provide a sense for the scale of the opportunity for onvansertib. But before we look at the absolute numbers of patients, I want to address why onvansertib can target these large populations. Fundamentally, there are 2 ways to approach drug development in oncology.
On the left-hand side, we have the approach where our drug targets a specific oncogenic driver mutation, such as ROS1 [ and RET ]. However, if you look to the right, you can see that this focus on a specific mutation significantly narrows the targeted patient population.
The second approach to oncology drug development is to inhibit a target that does not have an oncogenic alteration. As a PLK1 inhibitor, onvansertib is in this category, along with other large oncology drugs by PARP inhibitors, immunotherapy checkpoint inhibitors and anti-angiogenics, which are some of the most widely used cancer therapies ever developed. PLK1 is not mutated in cancer cells but rather is overexpressed by tumors and plays an integral role in tumor cell proliferation and survival.
If you look to the right, you can see that with this approach, the number of patients that can be positively impacted by onvansertib is much larger than for some of the oncogenic mutation-targeted therapies. So while our development efforts are highly focused on our lead mCRC program, we are also evaluating onvansertib's potential with other large cancer indications.
With this, I would like to turn the call over to Dr. Fairooz Kabbinavar, who is our Chief Medical Officer, to walk you through the exciting results from our metastatic PDAC and Small Cell Lung Cancer program. Not only do these data demonstrate onvansertib has efficacy against both of these difficult-to-treat diseases, but in PDAC and small cell lung cancer, we have efficacy signals for onvansertib monotherapy. Fairooz?
Fairooz Kabbinavar
Thank you, Mark. It's a pleasure to speak with all of you today. Let's start on Slide 8, highlighting the 3 different trials in our PDAC program. The first is a CRDF-001 PDAC Phase II trial. We first announced data from this trial in September 2022, and we have an important update to provide today. After that, I'll present some early results from an investigator-initiated biomarker discovery trial that we have not discussed publicly before. And finally, I'll share our conclusions from examining the data from these 2 PDAC trials that shines the light on path forward to advancing our PDAC programs to the frontline setting. Specifically, we'll be sharing with you the plan for a new investigator-initiated trial in first-line metastatic PDAC.
Slide 9. I'll start by focusing on CRDF-001 Phase II trial. Slide 10 shows the design of CRDF-001 Phase II trial. Enrollment criteria includes patients with metastatic PDAC who have progressed on frontline Gemzar/Abraxane combination chemotherapy, patients have measurable disease according to RECIST 1.1, an ECOG performance status of 0 or 1 and normal organ function.
This is a single-arm trial, so all patients will receive chemotherapy regimen of 5-Fluorouracil, leucovorin and nanoliposomal irinotecan every 2 weeks. And for the first 5 days of each 14-day chemotherapy cycle, patients receive onvansertib and 15-milligram per meter square dose on a daily basis. The brand end point is objective response rate according to RECIST 1.1, and disease control rate is the secondary endpoint.
On Slide 9 -- Slide 11, you can see that patients on onvansertib plus chemotherapy proved to have a higher response rate compared to historical controls. In this trial, we have 21 patients evaluable for radiographic response as of September 13, 2023 with 1 confirmed partial response and 3 partial responses that are waiting for confirmatory scan, giving us an objective response rate of 19%, 4 responders out of 21 patients. Compared to the historical benchmark, 19% objective response rate achieved in this trial is superior to the 7.7% response rate seen in the second-line setting. And it also comes very close to the frontline historical 23% objective response rate of Gem/Abraxane. So we are very excited about the results observed to date in this trial.
On Slide 12, we see the swimmer plot showing the patient responses to continued therapy over time. Importantly, 2 of the 3 partial responses still awaiting a confirmatory scan occurred at 6 months scan for patients 27 and patient 31.
On Slide 13, you can see in the spider plot how the responses from these 2 late responding patients deepened over time. And I hear well past the historical median progression-free survival of 3.1 month is the dotted line that you see in the middle of the graph there.
Slide 14 -- on Slide 14, we have the -- we see the [indiscernible] for the 23 evaluable patients of progression-free survival as of September 13, 2023. You can see that patients onvansertib plus chemotherapy appeared to have an improved progression-free survival compared to the historical control. The median progression-free survival in CRDF-001 trial is 5 months, and the historical control for second-line median progression-free survival is 3.1 months. Once again, our second-line data approaches the benchmark of first-line median PFS setting, which is 5.5 months.
The probability of being progression-free at 16 weeks from our trial is 56%. That data is not available for second-line historical-controlled patients. But for the first-line patients, the probability of being progression-free at 16 weeks is 48%. So all in all, the response rate and the median progression-free survival appeared to demonstrate a higher signal of efficacy for onvansertib plus chemotherapy population in this indication.
I'd like to point out that the waterfall plot on the previous slide presented data from 21 patients and the progression-free survival curve included 23 patients. This difference is because 2 patients will receive 2 cycles of treatment did not receive a post specialized scan before leaving the product. And so they don't have a radiographic evaluation to report.
The fact that these 2 patients locked before receiving a post-baseline scan underscores one of the important lessons from this trial. While the totality of the data I will discuss suggest that we are seeing a signal of efficacy from onvansertib, we believe that second-line patients on the trial may have a disease that has progressed too far for therapy to be optimally effective.
Second-line patients seem to progress rapidly without giving an experimental drug time to work. After discussing this data with our investigators, we believe that our planned shift to the finalized setting will allow us to have a greater opportunity to fight this challenging disease at an earlier stage when the chances of patients responding to treatment are the highest.
As you can see on Slide 15, I will now move on to the second metastatic PDAC trial, which is an investigator-initiated biomarker discovery trial. This trial is being conducted at OHSU Knight Cancer Institute. As I said earlier, this is the first time we're discussing this trial, and we are pleased by early results which support our planned shifts to the frontline setting.
On Slide 15, we show the design for this trial, which aims to determine the biological action and the molecular activity of onvansertib monotherapy in patients with refractive metastatic PDAC. One of the aspects of this trial that made it intriguing for us is the fact that it explores single-agent activity for onvansertib. Patients received 10 days of daily onvansertib as a monotherapy and a dose of 12 milligrams per meter squared.
Before starting treatment with onvansertib, patients get a tumor biopsy and a research blood draw. And at the conclusion of the 10 days of monotherapy, patients will receive another tumor biopsy and research blood draw. These biopsies and blood samples will be subject to the extensive multiomic analysis. After the 10 days of onvansertib monotherapy, patients going to receive standard of care only regardless of their response to onvansertib.
We are interested in participating in this unique trial because it would enable us for the first time to determine the sole biological action of onvansertib in tumors within a clinical setting.
On Slide 17, you can see the biomarker response data, including Ki67 and CA 19-9 for the 2 patients evaluated to date on this drug. Intriguingly, 1 of the 2 patients, #28, showed a robust biomarker response to the 10 days of onvansertib monotherapy. Ki67 is a marker of rapid cell turnover and tumor proliferation. And for patient 28, this level responded well with an 86% reduction in Ki67 when comparing the 3 different levels to the levels immediately after 10 days of treatment with onvansertib alone. This result is consistent with onvansertib's mechanism of action established in preclinical models, where it inhibits tumor cell proliferation by cell cycle G2 [indiscernible]. This is the first clinical demonstration of this mechanism of action.
CA 19-9 is the most extensively studied and validated serum biomarker in PDAC, which provides a clinically meaningful surrogate for response to treatment. In other words, a downward movement in CA 19-9 reflects the tumor response to treatment versus an upward moment reflects a lack of response. We are encouraged by the ability of onvansertib to provide an approximately 30% reduction in this clinical biomarker with only 10 days of monotherapy.
On the right hand of the slide, you will see the second patient who did not have a biomarker response. Ki67 remain unchanged in the pre- and post-treatment period, and the CA 19-9 increased at the 10-day mark. Thus far, we have had 1 biomarker responder and 1 nonresponder to onvansertib monotherapy. And both these patients have liver metastases, and their biopsies were taken from the liver [ mets ].
When we compare the biomarker data from patients 28 and 23, we found an important and intriguing difference, which appears to validate one of the critical findings we discussed on the colorectal cancer program call in August 2023. On our MCIC call, we discussed the role of cellular hypoxia as a hallmark of cancer and provided extensive preclinical data about onvansertib's role in the inhibited F1a, which have [ hypoxia-induced ] factor 1 alpha response pathway.
Returning now to this PDAC biomarker trial. When we looked at the whole genome transcriptome from patient 28's pre-treatment biopsy, we found that this patient has a much higher level of hypoxia-related gene expression than patient 23. And the post-treatment biopsy for patient 28 shows that the hypoxia-related gene expression was significantly reduced. This finding appears to once again validate onvansertib's role in anti-[indiscernible] and potentially explain patient 28's strong biomarker response to onvansertib monotherapy treatment. Overall, we believe that cellular hypoxia may be a biomarker for predicting response to onvansertib, and we plan to explore this in our future clinical products.
We do understand that 2 patients is a small number. But given the clear biomarker signal in the monotherapy trial, it gives us additional evidence of onvansertib's in the metastatic PDAC setting. When viewed together with the response rate and the survival data from the ongoing CRDF-001 trial, this support our broader conclusion about the future of metastatic PDAC program, and we have a signal of efficacy that is worth exploring in a new trial in the first-line setting.
Slide 18. As you can see on this slide, I'll be discussing this path forward in the first-line metastatic PDAC setting in the next slide.
Slide 19 shows the proposed design of the new Phase II trial that will combine onvansertib with the standard of care Gemzar and Abraxane. This investigator-initiated trial will be conducted at OHSU Knight Cancer Institute, which is the same institution that is conducting the current biomarker discovery trial. The enrollment criteria will include patients who are treatment-naive with an ECOG performance of 0 or 1. They'll have unresectable or locally advanced or metastatic pancreatic cancer with measurable disease according to RECIST 1.1. Patients will be divided into 2 cohorts on a nonrandomized basis. The first cohort of patients will receive 10 days of monotherapy as a lead-in, and there'll be biopsies in retail blood draws before and after treatment, similar to the biomarker discovery trial I just discussed. After the lead-in period, the patients will then move on to receive a combination of standard-of-care chemotherapy and onvansertib.
The second cohort of patients will not receive onvansertib monotherapy lead-in but will move straight to the combination regimen as shown on the right-hand side of the Slide 19. Importantly, we have preclinical data demonstrating synergy of onvansertib with Abraxane, which adds to our rationale for evaluating this combination in this product. This combination of regimen consists of gemcitabine or Gemzar and Abraxane on days 1, 8 and 15 of a 4-week cycle. Patients will receive daily onvansertib with chemotherapy on days 1 to 5, 8 to 12 and days 15 to 19. Patients will be monitored with blood work on a weekly basis.
The rationale for this twofold approach is to allow us to further explore biomarkers that will predict response to onvansertib. While in the second cohort, we'll determine the safety and efficacy of onvansertib plus the standard-of-care Gem/Abraxane, which could be informative for the planning of the future registration trial.
Shifting our program to the frontline setting is an important and exciting move for Cardiff Oncology and follows our internal assessment and investigator recommendations based on the clinical and preclinical data. We anticipate the trial will begin enrollment in the first half of 2024.
As you can see on Slide 20, I'll now move on to the next item on our agenda, where we will share results from the investigator-initiated trial in extensive-stage Small Cell Lung Cancer.
Slide 21. I'll start by sharing with you preclinical data in Small Cell Lung Cancer xenografts on this slide. On the right-hand side of the slide, you will see that treatment with onvansertib monotherapy results in reduction in tumor volume that is superior for CISPLATIN in both CISPLATIN sensitive and CISPLATIN resistant [ cell lines ]. Our goal then was to see if these encouraging results in the preclinical models showing single-agent activity with onvansertib could be translated to the clinical setting.
Slide 22 shows the design of the ongoing extensive-stage Small Cell Lung Cancer clinical trial. Importantly, like the PDAC biomarker trial, this is another example of exploring treatment with onvansertib as a monotherapy. However, in this trial, the treatment follows a more traditional clinical program -- clinical regimen.
The enrollment criteria is relatively simple. The trial includes patients who have relapsed after receiving 1 or 2 prior lines of therapy and have extensive-stage disease. This is a single-arm trial with 2-stage design. In the first stage, 15 patients will be enrolled. If 2 or more responses are seen, we will move to the second stage where an additional 20 patients will be added. The primary end point is objective response rate according to RECIST 1.1. The secondary objective is progression-free survival and overall survival.
The treatment scheme is as follows. Patients will receive 15 milligrams per meter squared of onvansertib monotherapy on a daily basis for the first 2 weeks of a 3-week cycle from day 1 to day 14 in a 21-day cycle. And then patients will have treatment-free days period from days 15 through day 21.
On Slide 23, we have the preliminary safety and efficacy results from this trial. Preliminary data shows that safety of the first 6 patients reviewed by the University of Pittsburgh Medical Center Institutional Review Board, the IRB has allowed the investigator to continue to enroll patients with no conditions [ adapt ].
On the efficacy side, 7 patients have been enrolled, of which 1 had a confirmed partial response, 3 have had stable disease and 3 have had progressive disease. The disease control rate, which includes partial responses and stable disease, is 57%. That is 4 of the 7 patients, as you can see on the slide.
The single partial response observed is very exciting to oncologists like me who treat Small Cell Lung Cancer, even in the small subset of 7 patients and is particularly important that such an early signal of efficacy is coming from an oral small molecule monotherapy.
On Slide 23 to 28, we have presented the baseline and post-cycle 2 scans for the patient in the trial who had a confirmed partial response. But before discussing the images, I want to remind you that small cell lung cancer is an extremely difficult disease to treat. For 30 long years, CISPLATIN and etoposide were the only standard-of-care treatment available for these patients. And then in 2019, in a study that I was involved in, izolizumab was added to this chemotherapy with improvement in survival to a little over 1 year, and this has become the new standard of care.
Once patients fail in the frontline setting, the options in second line and beyond are not very effective. The outcome for the second- or third-line refractory patients is extremely grim with the response rates that range between 18% to 25% range. And the median progression-free survival ranges between 2 to 3 months with an overall survival, again, a very abysmal 4 to 6 months.
At the end of the day, regardless of what chemotherapy agent we used, these numbers have remained unchanged. And hence, there's a significant and urgent unmet need to go deeper options for these patients.
Turning on to the scans. As you can see, on the baseline scan on the left-hand side, there's a fairly large tumor in the front of the chest in the anterior mediastinum. And if you look at the restaging scan down 6 weeks later after patients had received 2 cycles of treatment on the right-hand side, the tumor has shrunk dramatically. The investigator assessed this as a 50% shrinkage of the tumor, qualifying these patients to have a partial response. On the subsequent 6-week scans later, the partial response was confirmed.
I understand it is just 1 patient, but it is still very exciting, especially because this demonstrates a signal in activity for onvansertib. Our current plans are to continue enrolling in this trial by exploring the single-agent activity. But importantly, our expectation is that a future clinical path forward in Small Cell Lung Cancer is likely to include a combination of -- combination regimen of onvansertib and paclitaxel. While the onvansertib [indiscernible] data activity would give us reason to be optimistic, our preclinical data suggests the combination of onvansertib and chemotherapy would be the most powerful approach to treating this difficult disease.
Now I will hand things back over to Mark to close the call. Mark?
Mark Erlander
Well, thank you, Fairooz. Turning to Slide 25. We highlight our data readouts at Cardiff Oncology. Today, we have delivered on our guidance of sharing data on our metastatic PDAC and Small Cell Lung Cancer programs with the exciting results that Fairooz has just shared with you. The next anticipated milestone will be our lead program in first-line metastatic colorectal cancer, where we anticipate an interim readout from our randomized trial in mid-2024.
I would like to note that we have removed an estimated time of data release from the triple-negative breast cancer investigator-initiated trial as we are still in a dose-escalation phase of the trial. We will provide an update when possible. From a financial perspective, at the end of June, Cardiff Oncology had $89.4 million in cash. Our cash burn averages around $8 million per quarter, providing a cash runway into 2025.
In conclusion, we at Cardiff Oncology are very excited about the data we have shared with you today in metastatic PDAC and Small Cell Lung Cancer and also what we shared with you last month regarding metastatic CRC. Together, these achievements reflect the immense opportunity we see for onvansertib to provide a meaningful benefit to patients living with and fighting cancer.
With this, we are ready to take your questions. Operator?
Operator
[Operator Instructions] Our first question comes from the line of Marc Frahm of Cowen.
Marc Frahm
I guess moving forward with this first-line PDAC trial, I guess, with these early cohorts of patients, what would you view as kind of proof of concept that would justify moving into larger first-line trials?
Mark Erlander
Can you repeat that, Marc? It was kind of garbled at the end.
Marc Frahm
Sorry. Just as you get -- start getting data in the first-line trial, what would you view as kind of proof of concept to justify kind of expanding that program out from these initial running cohorts?
Mark Erlander
Oh, yes, yes. As you know, we're coming off some really exciting data in the second line. And there, we're having a 19% response rate. When we look at first line, as we noted in that one slide, 23% is the response rate. The PFS is a little over 5 months. So we'll be looking for a 50% increase in those response rates and PFS.
Marc Frahm
Okay. That's helpful. And then just in the -- kind of on the second-line trial, there's no more enrollment happening? Is that correct? These are all the patients that will ever be in that trial? And then, I guess, you mentioned the next update being from colorectal. But should we expect an update from this with a longer follow-up and maybe an attempt to hopefully confirm some of these responses that are still on but ongoing?
Mark Erlander
Yes. Thanks, Mark. Yes, we will be following up on -- in this Phase II trial in pancreatic. As you've noted, we'll be following up because we'll have some confirmatory scans. And we have a couple more patients, and then we're pretty much hitting what we had planned to do in this trial -- in this Phase II trial. So we are, in essence, in the wrapping up of this particular trial.
Operator
Please stand by for our next question, which comes from the line of Joe Catanzaro of Piper Sandler.
Joseph Catanzaro
I have maybe 2. First one, just wondering if you could speak a little bit more to the safety you're observing within the combination in pancreatic cancer. I guess I'm specifically interested in the rates of high-grade neutropenia that you may be seeing. And it looks like there were 2 discontinuations due to AE on the swimmers plot. Just wanted to see if maybe you could say what those were. And I have one follow-up.
Mark Erlander
Yes. I think what we probably should do there is follow up with you because we don't have those specifics here in the slide deck, Joe, I know we have a call with you coming up later today. But Fairooz, would you want to speak to those 2 in general?
Fairooz Kabbinavar
Yes. So there's 2 patients that came up with toxicity. Again, this is -- remember, this is a pancreatic cancer patients that have in the second- and third-line setting. And so it's a rapid decline in the functionality. And even with a little bit of toxicity, these patients have come off the study.
As far as the severity of toxicity, I have not seen any Grade 3 or 4 toxicity that required us to withhold treatment or decrease the dose of the patients. But we'll provide the details when we speak with you on one-on-one.
Joseph Catanzaro
Okay. And then I guess my follow-up, maybe sort of along the lines of Mark's earlier question on establishing proof of concept. I think if I remember back to last year, you had said that in second-line PDAC, you'd see proof of concept as a 20% ORR and median PFS of 6 months or greater. So appreciate small numbers here, but I guess what gives you confidence to move forward even if maybe you're coming up just short of that internal hurdle that you previously stated?
Mark Erlander
Thanks, Joe. Yes, we're coming off of -- the trial results are pretty much in line with what we were looking for. And I think also, the other thing that we're looking at is what is currently standard of care, which keep in mind is 7.7%, and the median PFS is at 3.1 months. So we are looking at this.
And then secondly is the exciting work that came out of the discovery trial, where we saw this really amazing response -- biomarker response with single monotherapy with onvansertib. So when we really look at that in totality, along with our preclinical data, that's really what made the decision to move to first line.
Operator
Our next question comes from the line of Alexandra Ramsey of William Blair.
Alexandra Ramsey
Congrats on the new data. So I had a couple of quick questions. The first one was on historical control data for PDAC, the 7.7% response rate. I think that says that that's from the label for [indiscernible]. And I was just wondering if you could kind of just illustrate for me the difference between that 7.7% response rate. And then I believe 7% response rate that was reported in the final overall survival analysis from NAPOLI-1, I was just kind of curious what the difference there is.
And then as my second question, I was just wondering if going forward, if outside of colorectal cancer, you're kind of planning for these other indications to be explored through investigator-sponsored trials to kind of preserve capital or if there's any indications that you think you might bring more in-house development going forward.
Mark Erlander
Sure. Thank you very much. The 7.7% comes from, as you know, the FDA insert, which is looking at confirmed responses. So that's where that comes from. The NAPOLI publication had hired but had many unconfirmed responses. So that's point number one. And so -- and we're very confident with the -- our trial results so far with the 4 PRs that we've seen.
Keep in mind that you notice that 2 of those PRs actually occurred with deepening responses and occurred 6 months out, so versus a 3.1 median PFS. So we're very excited about that data. I think going forward, as I mentioned on the call, we do believe that it's very capital-efficient to be able to explore these other indications initially through these investigator-initiated trials, and we would continue to do that.
Operator
Please standby for our next question, which comes from the line of Raghuram Selvaraju of H.C. Wainright.
Raghuram Selvaraju
I was wondering if you could comment on the broader regulatory environment at this time, particularly in regard to the use of partial responses, confirmed or unconfirmed, from single or non-randomized studies and if in a general sense, your strategy focusing on earlier-line settings is partly in keeping with what you see as the ongoing evolution of the regulatory environment within oncology.
Mark Erlander
Well, thank you, Ram, for that question. As you know, our plan right now in metastatic colorectal cancer in first line is a randomized trial where we combine with standard of care versus standard care alone. And we will continue to go down that road with the FDA agreeing to our plan. One thing I'll note there that's very exciting for us is that the FDA has agreed to us using the objective response rate in first-line setting for accelerated approval in a randomized trial.
So -- and I think as we look forward in these other trials, as we did mention on the call, we are looking at them in combination therapy. Having said that, we're very excited about the single-agent activity we've seen both in the pancreatic trial as well as in the monotherapy in small cell. But our clinical development path is really using a combination, which then -- would require then a randomized trial for accelerated approval.
Raghuram Selvaraju
Okay. And then another general question on the biomarker front is, do you feel that at this juncture, you have sufficient information from a biomarker perspective to have elucidated mechanistically what you feel is most important to elucidate about the MOA of onvansertib? And would you characterize the positioning at this point in your biomarker strategy to effectively be shifting more towards personalized medicine and identifying those patient subpopulations most likely to respond? Just give us a sense of where you feel you are in that process of the evolution of your biomarker strategy.
Mark Erlander
Yes. Thanks, Ram. First of all, we are seeing really great response rates in combination therapy. As you know, in second-line metastatic CRC, we had a 73% response rate without any kind of biomarker play per se, and that's why we moved into first line.
Having said all that, we continue to explore biomarkers as part of our programs because we do believe that understanding how and why patients are responding can only help future patients and future targeting of identifying those most likely to respond. But in high level, it's an ongoing process, and we will continue to see and report out what we find.
Raghuram Selvaraju
Okay. And then just very quickly, I'm assuming that nothing so far in your clinical experience with onvansertib would indicate that onvansertib is particularly effective in a specific subset of KRAS-mutant cancers. In other words, regardless of what the mutant KRAS phenotype, what the mutant KRAS background is, you would expect a roughly similar likelihood of responsiveness to onvansertib. Is that correct?
Mark Erlander
That is correct, and thank you for bringing forward that question because it's a very important one. We have reported already, as you know, within that Phase II or the second-line trial that we have activity across the board, across all mutant subtypes. This is really important because it differentiates us from the G12C-targeted therapies that really only address a very small sliver of metastatic colorectal cancer.
Operator
Please stand by for our next question, which comes from the line of Joel Beatty of Baird.
Joel Beatty
Congrats on the data. The first one is, could you discuss the likelihood of all 3 of the unconfirmed partial responses to confirm? And related to that, there also appears to be a few patients with stable disease that they got closed responses. Are there any potential for any of those patients to confirm later on?
Mark Erlander
Thanks, Joe, for that question. First of all, we're coming off of some pretty exciting data in our second-line trial. And as you know, we really, on purpose, showed that slide of the swimmer plot showing that you can see that we had -- and also the spider plot, where you see for these patients who did have a PR, they continue to have scan after scan a more deepening and deepening of response. We feel very confident about those kinds of responses because they're all the way up to 6 months, is -- which is double what the median PFS is.
Now as far as going forward into first line, obviously, we'll follow these patients and we will, as I've mentioned earlier, subsequently report that data. But we are -- we believe we have enough information now, enough -- strong enough data to be able to move into first line with this investigator-initiated trial that we described.
Joel Beatty
Great. And then I guess another question on the historical controls that showed a 7.7% response rate in second line. Could you discuss how your baseline characteristics in your study compared to the baseline characteristics of those patients?
Mark Erlander
Yes. They're similar. In essence, it's relapsed/refractory second line that have progressed on first line. And specifically, they exactly match that because these are patients that also progressed on Gem/Abraxane in first line.
Operator
At this time, I would now like to turn the conference back over to Mark Erlander for closing remarks. Sir?
Mark Erlander
Well, thank you, operator. And the slides of the investor call can be found in our home page. And really, you can look at www.cardiffoncology.com. And I would like to say, thank you all for your attention, and we are really excited to share this data with you all, and we look forward to sharing data in the future. Thank you.
Operator
This concludes today's conference call. Thank you for participating. You may now disconnect.
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