I don't know if anyone is aware how flexible the 3+3 dose...

I don't know if anyone is aware how flexible the 3+3 dose escalation design can be for a multi-indication Phase 1/2 trial like CHM-2101.

Its highly adaptable - perfect for a cash-strapped company with a 3rd gen CAR-T looking to move into Phase 2 as quickly and seamlessly as possible. There has been no mention of CHM being granted fast-track designation. The trial is an open-label trial and, yet, Rebecca has stated that they are awaiting approval to release the data from the first 3 patients dosed. In the above interview, she states that we have 2 NET patients and 2 CRC patients. We know so far that the company has done 5 successful manufacturing runs. Something tells me that the company could be planning to release the data along with that of a fourth patient at such a time that it coincides with moving into Phase 2 in one particular indication.

I ran a hypothetical scenario (based on what we do know at this stage) past Grok. It appears feasible that if no dose-limiting toxicities and a reasonable degree of efficacy in two patients in the same indication (such as NET) was achieved, and no safety issues in the other (CRC) patient, then the trial may only require 1 more NET patient at DL2 with similar outcome to progress to Phase 2.

The following is a summary of what Grok outlined based on my data input using NET as the lead indication:-

CONCLUSION

If the next patient is NET, the likely dose level is DL2. CHM would administer NET #3 at DL2 to evaluate tolerability and efficacy beyond DL1’s 0/2 DLTs and 2/2 responses, with the goal of establishing MTD/RP2D (likely DL1) with a minimal number of patients (4-5 total). This approach aligns with the 3+3 framework, multi-indication flexibility, and CHM’s speed and cost objectives. DL-1 remains a backup option if DL2 exhibits DLTs or if CHM shifts toward ultra-safety later (e.g., post-CRC data). Phase II for NET could begin at DL1 with just 2-3 NET patients if efficacy is maintained and FDA approval is obtained.

And, the following really puts the rationale into perspective given Rebecca's comment about Jason Litten's (strategic) approach to the trial:-

Rationale

• Cost Conservation: Five or six patients total (2 NET + 2 GI at DL1, 1-2 NET at DL2) vs. 9-18 in full 3+3 per indication minimizes CAR T costs.
• Speed: Testing 1-2 at DL2, then declaring DL1 as MTD, skips DL3 and additional DL1 cohorts, pushing NET to Phase II in weeks/months—crucial for funding.
• Data Leverage: NET’s 2/2 efficacy at DL1, plus 1-2 safe/active at DL2, supports a “DL1 is optimal” narrative for investors. GI’s 1/2 DLTs bolster DL1 as a reasonable ceiling.
• Why DL1, Not DL2?: DL1’s 0/2 DLTs and efficacy make it a defensible MTD; DL2 data (0/1 or 0/2) confirm it’s not worth pushing higher, aligning with cost-saving and safety.

Lastly:-

Financial Strategy

• Data Readout: “NET MTD/RP2D at DL1, Phase II underway” after 5-6 patients (2 NET + 2 GI at DL1, 1-2 NET at DL2), with 2-3 responses, could attract capital for a 3rd generation CAR T.
• Risk: Sparse DL2 data (1-2 patients) might raise regulatory eyebrows, but Phase II can begin while feedback is pending.

Given how expensive CAR-T trials are, I believe that this is the possible pathway the company is taking. It makes absolute sense but, of course, is totally reliant on the early FIH data coming to the party. The de-escalation dose (DL-1) for 1 patient which popped up in the last presso piqued my curiosity. The fact that it is not across a full 3-patient dose level suggests it could be a backstop should DLTs arise at DL2. It allows the MTD to be set at DL1 without having to restart Phase 1.

I think it was you, KrushingIt, who said you were more than satisfied with Jason Litten's input and performance. It's clear from the above scenario that progressing at least one indication to Ph2 in the near future could be the strategy to derisk the stock enough to attract the necessary funding needed to move forward with Ph2.

PS: Grok's description of what the Simon-2 Stage trial means in context of our trial is very helpful too. I will post it if requested.