Clinical trial NCT05374538
Conditions: Non-small Cell Lung Cancer
Keywords: KRAS G12C mutation AURA kinase VIC-1911 KRAS G12C sotorasib
Sponsor: Vitrac Therapeutics, LLC
Start date: 2022-11-09; Completion date: 2023-08-26
Enrollment: 3 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is a Phase 1a/1b study of aurora kinase A inhibitor VIC-1911 administered as monotherapy and in combination with sotorasib for the treatment of locally advanced or metastatic KRAS G12C-mutant non-small cell lung cancer(NSCLC).

Detailed description:
Selected subjects will include males and females age ≥18 years; histologically confirmed locally advanced or metastatic KRAS G12C-mutated NSCLC; received at least 1 prior line of cancer therapy with a PD-1 or PD-L1 inhibitor with or without platinum-based chemotherapy; recovered from all acute toxicities (≤ Grade 1) due to prior therapy; adequate renal and hepatic function; and no known history of significant cardiac, hepatic or ocular disease.

Dose Escalation Phase:

Following screening, a total of up to 36 subjects are anticipated to establish the dose limiting toxicity (DLT) and maximum tolerated doses (MTDs) of VIC-1911 monotherapy and VIC-1911 in combination with sotorasib therapy.

Cohort 1a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will receive VIC-1911 monotherapy. Up to 24 subjects are anticipated in this cohort.

Cohort 1b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy or are naïve to KRASG12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy. Up to 12 subjects are anticipated in this cohort.

A 3+3 dose escalation schema will be followed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of VIC-1911 and VIC-1911 plus sotorasib combination. A total of at least 6 subjects will be treated at the MTD in each group before initiating the Expansion Phase.

Expansion Phase:

Following screening, a total of 104 subjects with KRAS G12C-mutated locally advanced or metastatic NSCLC are anticipated to expand the disease treatment settings of VIC-1911 as monotherapy or in combination with sotorasib. VIC-1911 monotherapy and VIC-1911 plus sotorasib combination therapy will be administered orally at the MTDs established during the Dose Escalation Phase.

Cohort 2a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will receive VIC-1911 monotherapy. (n=29)

Cohort 2b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy.(n=29)

Cohort 2c: Subjects who are naïve to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy. (n=46)

VIC-1911 and sotorasib will be taken in the fasted state, 1 hour before or 2 hours after a meal.

Subjects who demonstrate clinical benefit (CR, PR or SD) will be allowed to continue therapy with VIC-1911 and sotorasib until progression of disease, observation of unacceptable adverse events, intercurrent illness or changes in the subject's condition that prevents further study participation.

Disease response will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST v.1.1).

Blood for hematology, coagulation parameters and serum chemistry determinations and urine will be collected, ECGs will be taken and ophthalmologic exams will be conducted during the study.

Blood will be taken for PK assessment of VIC-1911 and PD assessment of circulating tumor DNA biomarker determinations.

Tumor biopsies will be taken from consenting subjects at Screening and on-study for correlative biomarker determinations. Results will be correlated with clinical outcome.

Arms: arm 1: Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC refractory to or relapsed on prior KRASG12C inhibitor therapy will receive VIC-1911 monotherapy. arm 2: Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC refractory to or relapsed on prior KRASG12C inhibitor therapy or are naive to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy.

Only Dose Level 1 was opened and all 3 subjects received sotorasib 960 mg QD PO, VIC-1911 75 mg BID PO. arm 3: Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC refractory to or relapsed on prior KRASG12C inhibitor therapy will receive VIC-1911 monotherapy. arm 4: Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC refractory to or relapsed on prior KRASG12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy. arm 5: Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC naive to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy.
Interventions: intervention 1: VIC-1911 intervention 2: sotorasib
Intervention descriptions: intervention 1: VIC-1911 tablets for oral administration intervention 2: Sotorasib tablets for oral administration

Protocol documents:
Prot_SAP_000.pdf: 
Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
1 
November 11, 2022 
 
Amendment 2 
 
 
 
 
 
 
CLINICAL STUDY PROTOCOL 
 
Protocol Number: 
 
 
 
VIC-1911-01 
Protocol Title: 
A Phase 1a/1b Study of Aurora Kinase A Inhibitor 
VIC-1911 as Monotherapy and in Combination with 
Sotorasib for the Treatment of KRAS G12C-Mutant 
Non-Small Cell Lung Cancer 
 
Sponsor: 
VITRAC Therapeutics, LLC 
 
27 Strathmore Road 
Natick, MA  01760 
 
 
 
Original Protocol 
 
 
 
Date: 10 May 2022 
Amendment 1 
 
 
 
 
Date: 14 September 2022 
Amendment 2  
 
 
 
 
Date: 11 November 2022 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
2 
November 11, 2022 
 
Amendment 2 
 
 
INVESTIGATOR SIGNATURE PAGE 
 
I have reviewed the above-titled protocol and agree that it contains all the information necessary 
to conduct the study as required. I will conduct the trial in accordance with the principles of the 
International Conference on Harmonisation (ICH) Good Clinical Practice, the Declaration of 
Helsinki and the applicable U.S. Food and Drug Administration (FDA) regulations. 
I will maintain as confidential all written and verbal information provided to me by the Sponsor, 
including but not limited to, the protocol, electronic case report forms (eCRFs), investigator’s 
brochure, material supplied at investigator meetings, minutes of teleconferences, etc. Such material 
will only be provided as necessary to site personnel involved in the conduct of the trial, the 
Institutional Review Board (IRB) or local regulatory authorities. 
I will obtain written informed consent from each prospective trial subject or each prospective trial 
subject’s legal representative prior to conducting any protocol-specified procedures. The Informed 
Consent Document (ICD) used will have the approval of the IRB. 
I will maintain adequate source documents and record all observations, treatments and procedures 
pertinent to trial subjects in their medical records. I will accurately complete and submit the eCRFs 
supplied by the Sponsor in a timely manner. I will ensure that my facilities and records will be 
available for inspection by representatives of the Sponsor, the IRB or local regulatory authorities. 
I will ensure that I and my staff are available to meet with representatives of the Sponsor during 
regularly scheduled monitoring visits. 
I will report all serious adverse events (SAEs) according to the guidelines stipulated in the protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
3 
November 11, 2022 
 
Amendment 2 
 
 
1. 
SYNOPSIS 
Protocol Number: VIC-1911-01 
Name of Sponsor/Company: 
VITRAC Therapeutics, LLC 
Name of Investigational Product: 
VIC-1911 
Name of Active Ingredient: C23H22Cl2FN5O3 HCl  
Title of Study: A Phase 1a/1b Study of Aurora Kinase A Inhibitor VIC-1911 Monotherapy and in 
Combination with Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Lung Cancer 
Principal Investigators: The study will be conducted at Yale Cancer Center, Sarah Goldberg, MD, 
MPH, Principal Investigator (PI) and Study Chair; New York University Perlmutter Cancer Center, 
Vamsidhar Velcheti, MD, PI; University of California Davis Comprehensive Cancer Center, Jonathan 
Reiss, MD, PI; University of Maryland Cancer Center, Katherine Scilla, MD, PI; Emory University 
Winship Cancer Center, Jennifer Carlisle, MD, PI. Additional clinical sites may be added to complete 
enrollment in a timely manner. 
Study Period (42 months):  
Estimated Date First Subject Enrolled: October 2022 
Estimated Date Last Subject Completed: March 2026 
Phase of Development: 1 
 
Objectives:  
Primary: 
• Phase 1a (Dose Escalation Phase): To determine the safety, tolerability, maximum tolerated dose 
(MTD) and Recommended Phase 2 Dose (RP2D) of: 
• 
VIC-1911 monotherapy in subjects previously treated with KRAS G12C inhibitor therapy, 
• 
VIC-1911 in combination with sotorasib (LUMAKRAS™) in subjects previously treated with 
KRAS G12C inhibitor therapy, and  
• 
VIC-1911 in combination with sotorasib in subjects naïve to KRAS G12C inhibitor therapy 
• Phase 1b (Expansion Phase): To determine the objective response rate (ORR), defined as complete 
response (CR) or partial response (PR), for: 
• 
VIC-1911 monotherapy in subjects previously treated with KRAS G12C inhibitor therapy,  
• 
VIC-1911 in combination with sotorasib in subjects previously treated with KRAS G12C 
inhibitor therapy, and  
• 
VIC-1911 in combination with sotorasib in subjects naïve to KRAS G12C inhibitor therapy 
Secondary: 
The following parameters will be evaluated for VIC-1911 monotherapy and in combination with 
sotorasib:  
• Phase 1a (Dose Escalation Phase):  
• 
ORR 
• 
Duration of response (DoR) 
• 
Time to response (TTR) 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
4 
November 11, 2022 
 
Amendment 2 
 
 
Protocol Number: VIC-1911-01 
• 
Disease control rate (DCR), defined as stable disease (SD), CR or PR  
• 
Progression-free survival (PFS) 
• 
Overall survival (OS) 
• 
Pharmacokinetics (PK) of VIC-1911 monotherapy and in combination with sotorasib 
• 
Pharmacodynamics of tumor biomarker determinations pre- and on-study summarized and 
correlated with clinical outcome 
• 
In subjects refractory to or relapsed on prior KRAS G12C inhibitor therapy, the effect of prior 
KRAS G12C de novo resistance (KRAS G12C inhibitor treatment ≤ 3 months) versus KRAS 
G12C acquired resistance (KRAS G12C inhibitor treatment > 3 months) on clinical outcome 
• 
Phase 1b (Expansion Phase):  
• 
Safety and tolerability of VIC-1911 as monotherapy and in combination with sotorasib 
• 
Duration of response (DoR) 
• 
Time to response (TTR) 
• 
Disease control rate (DCR), defined as SD, CR or PR  
• 
Progression-free survival (PFS) 
• 
Overall survival (OS) 
• 
Pharmacodynamics of circulating tumor DNA (ctDNA) and tumor biomarker determinations 
pre- and on-study summarized and correlated with clinical outcome 
• 
In subjects refractory to or relapsed on prior KRAS G12C inhibitor therapy, the effect of prior 
KRAS G12C de novo resistance (KRAS G12C inhibitor treatment ≤ 3 months) versus KRAS 
G12C acquired resistance (KRAS G12C inhibitor treatment > 3 months) on clinical outcome 
Methodology:  
This is a non-randomized, open-label Phase 1a/1b study of aurora kinase A inhibitor VIC-1911 
administered as monotherapy and in combination with sotorasib for the treatment of locally advanced 
or metastatic KRAS G12C-mutant non-small cell lung cancer (NSCLC). 
Selected subjects will include males and females age ≥18 years with histologically confirmed locally 
advanced or metastatic KRAS G12C-mutated NSCLC, received at least 1 prior line of cancer therapy 
with a PD-1 or PD-L1 inhibitor with or without platinum-based chemotherapy (unless subject is not 
eligible or refuses chemotherapy or PD-1/PD-L1 therapy), previously treated with or naïve to KRAS 
G12C inhibitor therapy, recovered from all acute toxicities (< Grade 1) due to prior therapy, have 
adequate hematologic, renal and hepatic function and no known history of significant cardiac, hepatic 
or ocular disease. 
Phase 1a (Dose Escalation Phase):  
Following screening, a total of up to 36 subjects are anticipated to establish the MTDs of VIC-1911 
monotherapy and VIC-1911 in combination with sotorasib therapy.  
Cohort 1a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will 
receive VIC-1911 monotherapy. Up to 24 subjects are anticipated in this cohort.  
VIC-1911 monotherapy will be administered orally twice daily (b.i.d.) at doses of 25, 50, 75 and 90 mg 
(total daily doses of 50, 100, 150 and 180 mg) repeated every 28 days (=1 cycle). Subjects will take 
their VIC-1911 b.i.d. doses in the fasted state (1 hour before or 2 hours after the morning and evening 
meal), with the two doses approximately 12 hours apart.  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
5 
November 11, 2022 
 
Amendment 2 
 
 
Protocol Number: VIC-1911-01 
VIC-1911 Monotherapy Dose Escalation Levels: 
Dose Level 
VIC-1911 (PO b.i.d.) 
1 
25 mg  
2 
50 mg 
3 
75 mg 
4 
90 mg 
VIC-1911-related adverse events (AEs) will lead to dose reductions as indicated in Section 5.5.1.2.  
Cohort 1b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy or are 
naïve to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy. Up 
to 12 subjects are anticipated in this cohort.  
VIC-1911 will be administered orally twice daily (b.i.d.) at the doses indicated below on Days 1-4, 8-
11, and 15-18, repeated every 28 days (=1 cycle), and sotorasib will be administered once daily at the 
doses indicated below. Both VIC-1911 and sotorasib will be taken together in the fasted state (1 hour 
before or 2 hours after the morning meal and after the evening meal [VIC-1911 only]) with the VIC-
1911 b.i.d. doses approximately 12 hours apart. 
Combination VIC-1911 Plus Sotorasib Dose Escalation Levels: 
Dose Level 
VIC-1911 (PO b.i.d.)a 
Sotorasib (PO q.d.) 
1 
75 mg 
960 mg 
2 
150 mg 
960 mg 
3 
200 mg 
960 mg 
a Days 1-4 x 3 weeks q 28 days 
VIC-1911-related or sotorasib-related AEs will lead to individual dose reductions as indicated in 
Section 5.5.1.2. 
Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will be enrolled 
alternatingly into Cohort 1a (VIC-1911 monotherapy) and Cohort 1b (VIC-1911 plus sotorasib) by dose 
level (e.g., Dose Level 1 in Cohort 1a will be filled, then Dose Level 1 in Cohort 1b, then Dose Level 
2 in Cohort 1a, etc.). In Cohort 1b, VIC-1911 pharmacokinetics will be analyzed from Dose Level 1 
before Dose Level 2 is initiated to assess the impact of co-administration of VIC-1911 plus sotorasib 
on the pharmacokinetics of VIC-1911. If necessary, a dose adjustment to VIC-1911 will be made prior 
to initiating Dose Level 2. This information will be used to make a dose adjustment for Dose Level 3, 
if necessary.   
A 3+3 dose escalation schema will be followed for each cohort. A total of 3 subjects per cohort will be 
dosed and followed for 28 days through Cycle 1 for dose limiting toxicity (DLT). If 0 of 3 subjects 
experiences a DLT in Cycle 1, the next higher dose level cohort will open. However, if a DLT is 
experienced in 1 of 3 subjects, the cohort will be expanded to 6 subjects. If 2 or more of 6 subjects per 
cohort experience DLT, further dose escalation will be subject to Safety Review Committee (SRC) 
review and recommendation. The highest dose level below the dose level eliciting DLT in ≥ 2 of 6 
subjects will be declared the VIC-1911 monotherapy MTD or the combination VIC-1911 plus sotorasib 
MTDs. A total of 6 subjects will be treated at the MTD(s) in each cohort.  
For dose de-escalation, if 1 of 3 subjects experiences a DLT at the de-escalated dose level, the cohort 
will be expanded to 6 subjects. If ≥ 2 of 6 subjects at that dose level experience a DLT, no further 
subjects will be treated at that dose level and the next lower dose level to enroll 0 of 3 or < 2 of 6 
subjects without DLT will be declared the MTD.  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
6 
November 11, 2022 
 
Amendment 2 
 
 
Protocol Number: VIC-1911-01 
Subjects in all cohorts who demonstrate clinical benefit (CR, PR or SD) will be allowed to continue 
therapy with VIC-1911 monotherapy or VIC-1911 and sotorasib combination therapy until progression 
of disease (unless the subject is still benefiting clinically in the opinion of the treating physician, after 
discussion with the Medical Monitor, as described in Section 7.1.1.), observation of unacceptable AEs, 
intercurrent illness or changes in the subject’s condition that prevents further study participation.   
DLT is defined as any one of the following events considered at least possibly related to VIC-1911 
and/or sotorasib occurring within the first 28 days of study treatment (=DLT evaluation period): 
• Grade 4 hematologic toxicity for > 1 day 
• Grade 3 febrile neutropenia (defined as absolute neutrophil count (ANC) < 1000/mm3 with a single 
temperature of ≥ 38.3C [≥ 101F] or sustained temperature of ≥ 38.0C [≥ 100.4F] for more than 
1 hour)  
• Grade 3 hematologic toxicity with complications (e.g., thrombocytopenia with bleeding) 
• Failure of Grade 3 thrombocytopenia, ANC or hemoglobin (Hb) to recover to Grade ≤ 1 within 4 
weeks despite the use of platelet and red blood cell (RBC) transfusions and/or growth factors 
• > Grade 3 non-hematologic toxicity not due to disease progression (excluding nausea, vomiting, 
constipation, pain, diarrhea or rash that is adequately controlled with supportive care and resolves 
to ≤ Grade 2 within 48 hours), or electrolyte disturbances unresponsive to correction within 24 
hours 
• Laboratory abnormalities that satisfy the 3 components of Hy’s Law of drug-induced liver injury: 
1) ALT or AST elevation ≥ 3 times the upper limit of normal (ULN), 2) total bilirubin elevation > 
2 times the ULN without initial findings of cholestasis (i.e., absence of alkaline phosphatase activity 
> 2 times the ULN), and 3) no other reason to explain the combination of increased ALT/AST and 
total bilirubin, such as viral hepatitis, preexisting or acute liver disease, or another drug capable of 
causing the observed injury  
• A treatment interruption for ≥ Grade 3 drug-related toxicity in Cycle 1 exceeding 7 days or inability 
to begin Cycle 2 for > 7 days due to drug-related toxicity. 
• Other important medical event not clearly due to underlying disease or extraneous causes  
A DLT evaluable subject is one who receives study treatment and does not meet the criteria for subject 
replacement during the DLT evaluation period. 
No intra-subject dose escalation will be allowed from previous dose levels until the subject has received 
≥ 3 cycles of their assigned dose, and all subjects at the higher dose level have completed Cycle 1 at 
that dose level (e.g., 3 – 6 subjects, as required to establish safety of the higher dose level) and no ≥ 
Grade 3 toxicity, irrespective of causality, was observed during the previous treatment cycle. Subjects 
who experience a DLT may continue treatment in subsequent cycles at the next lower dose level(s) 
until disease progression (or until no longer benefiting clinically) or unacceptable toxicity.  
Subjects who experience DLT at the first dose level in each cohort will not be dose-reduced and will 
be discontinued.  
A total of at least 6 subjects will be treated at the MTD in each group before initiating the Expansion 
Phase. 
An SRC, consisting of the actively recruiting investigators, Sponsor Medical Monitor, and study staff, 
will review safety and efficacy data from each cohort monthly or more often as necessary. Intermediate 
dose levels may be added if it is recommended to do so by the SRC.  
Phase 1b (Expansion Phase): Following screening, a total of 104 subjects with KRAS G12C-mutated 
locally advanced or metastatic NSCLC are anticipated to expand the disease treatment settings of VIC-


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
7 
November 11, 2022 
 
Amendment 2 
 
 
Protocol Number: VIC-1911-01 
1911 as monotherapy or in combination with sotorasib. VIC-1911 monotherapy and VIC-1911 plus 
sotorasib combination therapy will be administered orally at the MTDs/RP2Ds established during the 
Dose Escalation Phase. 
VIC-1911 and sotorasib will be taken in the fasted state, 1 hour before or 2 hours after a meal. VIC-
1911 dose reductions for suspected VIC-1911-related toxicity will be followed in accordance with those 
established in the Dose Escalation Phase. Sotorasib dose reductions for suspected sotorasib-related 
toxicity will be 480 mg q.d. (Dose Level -1) and 240 mg q.d. (Dose Level -2) in accordance with the 
LUMAKRAS U.S. Product Label. Further detail on dose reduction guidelines for VIC-1911 and 
sotorasib are found in Section 5.5.1.2. 
Subjects who demonstrate clinical benefit (CR, PR or SD) will be allowed to continue therapy with 
VIC-1911 and sotorasib until progression of disease (unless the subject is still benefiting clinically in 
the opinion of the treating physician, after discussion with the Medical Monitor, as described in Section 
7.1.1.), observation of unacceptable AEs, intercurrent illness or changes in the subject’s condition that 
prevents further study participation.   
The statistical objective is the evaluation of the ORR, defined as CR or PR. The sample sizes are based 
on Simon’s 2-stage optimal design.   
Cohort 2a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will 
receive VIC-1911 monotherapy. The null hypothesis that the true OR rate (p0) ≤ 5% will be tested 
against a one-sided alternative true OR rate (p1) ≥ 20%. In the first stage, 10 subjects will be accrued. 
If there are 0 ORs in these 10 subjects, the cohort will be terminated due to futility. If there is at least 1 
OR in these 10 subjects, 19 additional subjects will be accrued for a total of n = 29 evaluable subjects. 
The null hypothesis will be rejected if 4 or more responses are observed in a total of 29 evaluable 
subjects. The design yields a type 1 error rate of 0.05% and power of 80% when the true response rate 
is at least 20% and provides evidence of clinical utility to move forward with continued clinical 
development in this patient population.  
Cohort 2b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will 
receive VIC-1911 plus sotorasib combination therapy. The null hypothesis that the true OR rate (p0) ≤ 
5% will be tested against a one-sided alternative true OR rate (p1) ≥ 20%. In the first stage, 10 subjects 
will be accrued. If there are 0 ORs in these 10 subjects, the cohort will be terminated due to futility. If 
there is at least 1 OR in these 10 subjects, 19 additional subjects will be accrued for a total of n = 29 
evaluable subjects. The null hypothesis will be rejected if 4 or more responses are observed in a total 
of 29 evaluable subjects. The design yields a type 1 error rate of 0.05% and power of 80% when the 
true response rate is at least 20% and provides evidence of clinical utility to move forward with 
continued clinical development in this patient population.  
Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will be enrolled 
alternatingly into Cohort 2a (VIC-1911 monotherapy) and Cohort 2b (VIC-1911 plus sotorasib) (e.g., 
one subject in Cohort 2a, next subject in Cohort 2b, next subject in Cohort 2a, etc.). 
Cohort 2c: Subjects who are naïve to KRAS G12C inhibitor therapy will receive VIC-1911 plus 
sotorasib combination therapy. The null hypothesis that the true OR rate (p0) ≤ 30% will be tested 
against a one-sided alternative true OR rate (p1) ≥ 50%. In the first stage, 15 subjects will be accrued. 
If there are 5 or fewer ORs in these 15 subjects, the cohort will be terminated due to futility. If there is 
at least 6 ORs in these 15 subjects, 31 additional subjects will be accrued for a total of n = 46 evaluable 
subjects. The null hypothesis will be rejected if 19 or more responses are observed in a total of 46 
evaluable subjects. The design yields a type 1 error rate of 0.05% and power of 80% when the true 
response rate is at least 50% and provides evidence of clinical utility to move forward with continued 
clinical development in this patient population. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
8 
November 11, 2022 
 
Amendment 2 
 
 
Protocol Number: VIC-1911-01 
A sample size of n = 46 evaluable subjects also yields a type 1 error rate of 0.05% and power of 79% 
when the median PFS is 10 months (from 6 months historical) based on a one-sample log-rank test.  
During the Expansion Phase, we will use continuous monitoring for excess toxicity using a Popcock-
type boundary,32 with the following assumptions: DLT event probability = 0.30 (30%) with 0.05 (5%) 
desired probability of stopping early.  
The maximum planned sample sizes for the Expansion Phase Cohorts 2a and 2b are n = 29 each. In 
each of these cohorts, sequential boundaries will be used to monitor the rates of DLTs. The accrual will 
be halted if excessive DLTs are seen, that is, if the number of subjects with a DLT is equal to or exceeds 
bn out of n subjects with full follow-up through C1D28. This is a Pocock-type stopping boundary that 
yields the probability of crossing the boundary at most (probability of early stopping) when the rate of 
DLT is equal to the acceptable rate (event probability θ). For the maximum planned samples sizes of n 
= 29 for each Cohorts 2a and 2b, the boundary is equivalent to testing the null hypothesis, after each 
subject, that the event rate is equal to 0.3, using a one-sided test level of 0.017846.  
The maximum planned sample size for the Expansion Phase Cohort 2c is n = 46. In this cohort, 
sequential boundaries will be used to monitor the rates of DLTs. The accrual will be halted if excessive 
DLTs are seen, that is, if the number of subjects with a DLT is equal to or exceeds bn out of n subjects 
with full follow-up through C1D28. This is a Pocock-type stopping boundary that yields the probability 
of crossing the boundary at most (probability of early stopping) when the rate of DLT is equal to the 
acceptable rate (event probability θ). For the maximum planned samples size of n = 46 for Cohort 2c, 
the boundary is equivalent to testing the null hypothesis, after each subject, that the event rate is equal 
to 0.3, using a one-sided test level of 0.011900. 
Each cohort in the Expansion Phase will be stopped if the number of subjects with a DLT is equal to or 
exceeds bn out of n subjects with completed follow up through C1D28. See Section 11.2. 
An SRC, consisting of the actively recruiting investigators, Sponsor Medical Monitor, and study staff, 
will review safety and efficacy data from each cohort monthly or more often as necessary.  
Study Assessments: 
Blood for hematology, coagulation parameters and serum chemistry determinations will be collected 
within 28 days prior to Cycle 1 Day 1; on Days 1 and 15 of Cycles 1-3; on Day 1 of each subsequent 
cycle and at the End of Treatment Visit.  
Urine will be collected for urinalysis within 28 days prior to Cycle 1 Day 1, on Day 1 of each subsequent 
cycle and at the End of Treatment visit. 
Electrocardiograms (ECGs) will be taken within 28 days prior to Cycle 1 Day 1, pre-dose and 
approximately 2 hours post-dose on Cycle 1 Day 1 and Day 15, and at the End of Treatment visit. 
Ophthalmic exams will be conducted within 28 days prior to Cycle 1 Day 1 and at the End of Treatment 
visit. Additional ophthalmologic examinations will be conducted during the study, if clinically 
indicated. Subjects should be educated on, and be instructed to, immediately report any signs of 
potential ocular toxicity so that the toxicity is identified and managed in a timely fashion. 
Blood for PK assessment of VIC-1911 plasma concentrations will be collected at Cycle 1 Day 1 and 
Day 15 pre-dose, 15 and 30 minutes, 1, 2, 4, 8 and 24 hours following the first daily dose, and pre-first 
dose Cycles 2, 4 and 6. On Cycle 1 Day 1 and Day 15, the evening dose of VIC-1911 will be held and 
subjects will receive only a single morning dose of VIC-1911 to collect a full pharmacokinetic profile 
following a single dose of study drug at steady state (Dose Escalation Phase only). 
Blood for assessment of ctDNA will be collected in the Expansion Phase Cohorts 2b and 2c pre-dose 
Cycle 1 Day 1 and at progression of disease for biomarker assessment.  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
9 
November 11, 2022 
 
Amendment 2 
 
 
Protocol Number: VIC-1911-01 
If clinically feasible, tumor biopsies will be collected on all subjects (Dose Escalation and Expansion 
phases) at Screening (archived or fresh) and on subjects in the Expansion Phase only at Cycle 3 Day 1 
and at time of progression for biomarker assessment.  
Results of ctDNA and tumor biomarker assessment also will be correlated with clinical outcome (e.g., 
objective response, disease progression, resistance development). 
Disease assessments will be based on computed tomography (CT) or magnetic resonance imaging 
(MRI). Assessments will be obtained every 8 weeks until documented progressive disease (PD).   
Number of Subjects and Centers (planned): Phase 1a (Dose Escalation Phase): Up to 36 subjects are 
anticipated. Phase 1b (Expansion Phase): Up to 104 subjects are anticipated. The total number of 
subjects anticipated for the study is up to 140 across 5 clinical sites. Additional clinical sites may be 
added to complete enrollment in a timely manner. 
Duration of Study: Accrual in the Dose Escalation Phase is expected to be 18 months. Accrual in the 
Expansion Phase is expected to be 18 months, with the last subject followed for up to 6 months. The 
total study duration is expected to be 42 months. The anticipated accrual rate in the Dose Escalation 
Phase is ~ 2 – 3 subjects per month, and in the Expansion Phase is ~6 subjects per month. 
Inclusion Criteria: 
1. Males and females  18 years of age 
2. Have locally advanced or metastatic histologically or cytologically confirmed NSCLC, KRAS 
G12C-mutated 
3. The presence of a KRAS G12C mutation should be established prior to entry as assessed in a 
CLIA qualified laboratory. Testing may be done on tumor tissue (archival or fresh) or on ctDNA 
from blood.   
4. Have received at least 1 prior line of cancer therapy with a PD-1 or PD-L1 inhibitor with or 
without platinum-based chemotherapy (unless subject is not eligible or refuses chemotherapy or 
PD-1/PD-L1 therapy) and have documented progression of disease on all prior cancer therapies  
5. Phase 1a (Dose Escalation Phase): 
5.1 Cohort 1a: (VIC-1911 monotherapy): Locally advanced or metastatic NSCLC refractory to 
or relapsed on at least 1 prior cancer therapy as noted above, and relapsed/refractory on KRAS 
G12C inhibitor therapy as the most recent cancer therapy prior to study 
5.2 Cohort 1b: (VIC-1911 plus sotorasib): Locally advanced or metastatic NSCLC:  
5.2.1 Refractory to or relapsed on at least 1 prior cancer therapy as noted above, and 
relapsed/refractory on KRAS G12C inhibitor therapy as the most recent cancer therapy 
prior to study, or  
5.2.2 Refractory to or relapsed on at least 1 prior cancer therapy as noted above, and naïve to 
KRAS G12C inhibitor therapy  
6. Phase 1b (Expansion Phase):  
6.1 Cohort 2a: (VIC-1911 monotherapy): Locally advanced or metastatic NSCLC refractory to 
or relapsed on at least 1 prior cancer therapy as noted above, and relapsed/refractory on KRAS 
G12C inhibitor therapy as the most recent cancer therapy prior to study 
6.2 Cohort 2b: (VIC-1911 plus sotorasib): Locally advanced or metastatic NSCLC refractory to 
or relapsed on at least 1 prior cancer therapy as noted above, and relapsed/refractory on KRAS 
G12C inhibitor therapy as the most recent cancer therapy prior to study 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
10 
November 11, 2022 
 
Amendment 2 
 
 
Protocol Number: VIC-1911-01 
6.3 Cohort 2c: (VIC-1911 plus sotorasib): Locally advanced or metastatic NSCLC refractory to 
or relapsed on at least 1 prior cancer therapy as noted above, and naïve to KRAS G12C 
inhibitor therapy  
7. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 
8. Have discontinued previous treatments for cancer, except for sotorasib for subjects to receive 
VIC-1911 plus sotorasib combination treatment, and have resolution, except where otherwise 
stated in the inclusion criteria, of all clinically significant toxic effects of prior cancer treatment, 
surgery, or radiotherapy to Grade ≤ 1  
9. Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2  
10. Life expectancy of ≥ 3 months  
11. Subjects with brain metastases: 
11.1 KRAS G12C inhibitor naïve: Subjects with clinically stable (i.e., no increase in 
corticosteroid requirement) asymptomatic brain metastases are allowed without prior local 
therapy, as long as all lesions are each ≤ 1 cm. Prior local therapy is required (e.g., 
stereotactic radiosurgery [SRS], stereotactic body radiation therapy [SBRT], or surgery) 
for any lesion > 1 cm or any lesion that is symptomatic 
11.2 KRAS G12C inhibitor pretreated: Subjects with clinically stable (i.e., no increase in 
corticosteroid requirement) asymptomatic brain metastases following prior local therapy 
(e.g., SRS, SBRT or surgery) are allowed    
12. Adequate hematologic without ongoing transfusion support: 
12.1 Hemoglobin (Hb) ≥ 8 g/dL 
12.2 Absolute neutrophil count (ANC) ≥ 1.0 x 109 cells/L 
12.3 Platelets ≥ 75 x 109 cells/L 
13. 
Adequate renal and hepatic function: 
13.1 Calculated creatinine clearance ≥ 50 mL/minute x 1.73 m2 per the Cockcroft-Gault formula 
13.2 Total bilirubin ≤ 1.5 times the ULN, unless due to Gilbert’s disease, or < 3 times the ULN 
for subjects with liver metastases 
13.3 ALT/AST ≤ 2 times the ULN, or < 3 times the ULN for subjects with liver metastases 
14. Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women 
of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone 
a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months 
(i.e., who has had menses any time in the preceding 24 consecutive months). Sexually active 
WCBP and male subjects must agree to use adequate methods to avoid pregnancy (oral, 
injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier 
contraceptive with spermicide; or vasectomized partner) throughout the study and for 28 days 
after the completion of study treatment.  
15. Ability to provide written informed consent 
Exclusion Criteria: 
1. Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial 
infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) 
Class III or Class IV  
2. QT interval corrected for rate (QTc) > 480 msec on the ECG obtained at Screening using 
Fridericia method for QTc calculation 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
11 
November 11, 2022 
 
Amendment 2 
 
 
Protocol Number: VIC-1911-01 
3. Medications that are inhibitors or inducers of UDP-glucuronosyltransferases (UGTs) are 
prohibited in the Dose Escalation Phase 
4. History of corneal epithelial cysts or other ocular events leading to blurred vision, or has 
medically relevant abnormalities identified on screening ophthalmologic examination  
5. Symptomatic pneumonitis/interstitial lung disease requiring medical intervention 
6. Symptomatic central nervous system metastasis 
7. Leptomeningeal carcinomatosis 
8. Inability to swallow oral medication 
9. Gastrointestinal conditions that could impair absorption or tolerance of study drugs 
10. Current hematologic malignancies 
11. Second, active primary solid tumor malignancy that, in the judgement of the Investigator or 
Sponsor Medical Monitor, may affect the interpretation of results, with the exception of 
carcinoma in situ of any origin, non-muscle invasive bladder cancer, and Gleason < 3+3 prostate 
cancer 
12. Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis 
C virus (HCV) requiring treatment within the last week prior to study treatment 
13. Other active infection requiring IV antibiotic usage within the last week prior to study treatment 
14. Unable to tolerate marketed dose of KRAS G12C inhibitor on prior therapy for subjects to be 
enrolled in the combination VIC-1911 plus sotorasib treatment cohorts. Alternatively, these 
subjects may be able to enroll in the VIC-1911 monotherapy treatment cohort, upon discussion 
with the Medical Monitor and Study Chair. 
15. Previous MEK or EGFR inhibitor therapy  
16. Any other medical intervention or other condition which, in the opinion of the Principal 
Investigator, could compromise adherence to study requirements or confound the interpretation 
of study results 
17. Receipt of an investigational product on a clinical trial within 5 elimination half-lives or within 
28 days, whichever is shorter, prior to C1D1 on this study, or currently enrolled in a clinical trial 
involving an investigational product or any other type of medical research judged not to be 
scientifically or medically compatible with this study 
18. Previously completed or withdrawn from any other study investigating an aurora kinase A 
inhibitor 
19. Known hypersensitivity to VIC-1911 or its components 
20. If female, pregnant, breast-feeding, or planning to become pregnant 
Criteria for Evaluation: 
Safety: Safety will be assessed through the monitoring of AEs, clinical laboratory parameters 
(hematology, coagulation parameters, serum chemistry, urinalysis), vital sign measurements, 
electrocardiograms (ECGs), ophthalmologic examinations and physical examinations. AEs will be 
classified according to the Medical Dictionary for Regulatory Affairs (MedDRA, version 24.0 or 
higher) and graded according to the National Cancer Institute Common Terminology Criteria for 
Adverse Events (NCI CTCAE, version 5.0 or higher). 
Efficacy: Efficacy assessments will be determined on the basis of CT and/or MRI scans with best ORR 
at protocol-specified time points. DoR, TTR, DCR, PFS, and OS will be determined.  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
12 
November 11, 2022 
 
Amendment 2 
 
 
Protocol Number: VIC-1911-01 
Pharmacokinetics: Pharmacokinetic determinations of VIC-1911 will be made. Additionally, any 
identified drug-drug interactions (DDIs) between VIC-1911 and sotorasib will be characterized.   
Pharmacodynamics: The results of ctDNA and tumor biomarker determinations will be correlated with 
clinical outcome (e.g., objective response, disease progression, resistance development). 
Investigational Product, Dosage and Mode of Administration: VIC-1911 is an inhibitor of aurora 
kinase A (AURA kinase). VIC-1911 is supplied in 10 mg and 25 mg tablets for oral administration. 
VIC-1911 should be stored at room temperature (15 - 25C), protected from light.  
Sotorasib (LUMAKRAS) is commercially available and will be provided by the investigational site. 
Reference Therapy: None 
Statistical Methods: 
Efficacy Endpoints and Analyses: Response rates (ORR [CR+PR]) and DCR [CR+PR+SD]) will be 
summarized using number and percentage of subjects with a best response of CR, PR, SD or PD 
assessed by RECIST v 1.1, along with 2-sided, 95% confidence intervals for the proportions.  
In subjects refractory to or relapsed on prior KRAS G12C inhibitor therapy, the effect of KRAS G12C 
de novo resistance (prior KRAS G12C inhibitor treatment ≤ 3 months) versus KRAS G12C acquired 
resistance (prior KRAS G12C inhibitor treatment > 3 months) on clinical outcome will be determined. 
Determinations of DoR, TTR, PFS and OS will be made using the Kaplan-Meier product- limit method. 
Subjects who do not have disease response (for TTR) or progression (for PFS, OS) will be censored at 
the last follow-up time.  
DoR will be calculated from the date of first response to the date of progression or death. 
TTR will be calculated from the date of first treatment to the date of first response. PFS will be 
calculated from the date of first treatment to the date of first evidence of progression or death. 
OS will be calculated from the date of first treatment to the date of death from any cause; subjects who 
do not experience death will be censored at the last follow-up time.  
SAS Version 9.4 for Windows (SAS Institute, Cary, NC) or higher will be used for all analyses. 
Pharmacokinetic Endpoint Analyses: Because plasma concentrations will be determined at a limited 
number of time points during the study, a complete pharmacokinetic profile of VIC-1911 at each dose 
level may not be possible. Limited pharmacokinetic analyses will be performed, as VIC-1911 
monotherapy and when given in combination with sotorasib. Additionally, any identified DDIs between 
VIC-1911 and sotorasib will be characterized.  
Pharmacodynamic Endpoint Analyses: Results of ctDNA and tumor biomarker assessment will be 
summarized and correlated with clinical outcome (e.g., objective response, disease progression, 
resistance development). 
Safety Endpoints and Analyses: Safety endpoints for AEs include the following: incidences of all 
treatment-emergent adverse events (TEAEs) and all serious adverse events (SAEs); incidences of 
TEAEs and SAEs by severity; incidences of TEAEs and SAEs by relationship to study medications; 
incidences of all Grade 3 and 4 TEAEs and by severity and relationship to study medications; and 
discontinuation of subjects from the study due to AEs or death. Safety endpoints for AEs, clinical 
laboratory tests, vital signs, ECGs, ophthalmologic examinations and physical examinations will be 
specified in the statistical analysis plan. All safety endpoints will be summarized using descriptive 
statistics. 
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
13 
November 11, 2022 
 
Amendment 2 
 
 
TABLE OF CONTENTS 
1. 
SYNOPSIS ...................................................................................................................3 
2. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................19 
3. 
INTRODUCTION ......................................................................................................24 
3.1. 
VIC-1911 Summary ....................................................................................................24 
3.1.1. 
Preclinical Pharmacology ...........................................................................................24 
3.1.1.1. 
In Vitro ........................................................................................................................24 
3.1.1.2. 
In Vivo .........................................................................................................................29 
3.1.2. 
Preclinical Pharmacokinetics ......................................................................................33 
3.1.3. 
Preclinical Toxicology ................................................................................................34 
3.2. 
Rationale for Targeting RAS Mutations in NSCLC ...................................................34 
3.3. 
Rationale for Targeting AURA Kinase in NSCLC ....................................................35 
3.4. 
Possible Risks and Side Effects ..................................................................................37 
3.4.1. 
VIC-1911 Monotherapy Phase 1 Study in Advanced Solid Tumors ..........................37 
3.4.2. 
Clinical Studies of Other AurA Kinase Inhibitors ......................................................38 
3.4.3. 
Sotorasib (LUMAKRAS™) .......................................................................................38 
3.4.3.1. 
Warnings and Precautions23 ........................................................................................38 
3.4.3.2. 
Adverse Reactions ......................................................................................................39 
3.4.4. 
Potential Overlapping Toxicities of VIC-1911 in Combination with 
Sotorasib .....................................................................................................................39 
3.5. 
Dose Rationale ............................................................................................................39 
3.5.1. 
VIC-1911 ....................................................................................................................39 
3.5.2. 
Sotorasib .....................................................................................................................39 
4. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................41 
4.1. 
Primary Objectives .....................................................................................................41 
4.2. 
Secondary Objectives .................................................................................................41 
5. 
INVESTIGATIONAL PLAN .....................................................................................43 
5.1. 
Overall Study Design ..................................................................................................43 
5.2. 
Number of Subjects and Centers ................................................................................47 
5.3. 
Treatment Assignment ................................................................................................47 
5.4. 
Duration of Study .......................................................................................................48 
5.5. 
Dose Adjustment Criteria ...........................................................................................48 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
14 
November 11, 2022 
 
Amendment 2 
 
 
5.5.1. 
Safety Criteria for Adjustment or Stopping Doses .....................................................48 
5.5.1.1. 
Toxicity Grading Criteria ...........................................................................................48 
5.5.1.2. 
Dose Modifications and Dose Reductions ..................................................................48 
5.5.1.3. 
Schedule Adjustments for Toxicity ............................................................................51 
5.5.2. 
Supportive Care Guidelines ........................................................................................51 
5.6. 
Criteria for Study Termination ...................................................................................52 
6. 
STUDY POPULATION .............................................................................................53 
6.1. 
Subject Inclusion Criteria ...........................................................................................53 
6.2. 
Subject Exclusion Criteria ..........................................................................................55 
6.3. 
Discontinuation of Subjects ........................................................................................56 
6.3.1. 
Replacement of Study Subjects ..................................................................................56 
7. 
TREATMENT OF SUBJECTS ..................................................................................58 
7.1. 
Description of Treatment Plan ....................................................................................58 
7.1.1. 
Treatment Duration .....................................................................................................58 
7.2. 
Concomitant Medications ...........................................................................................58 
7.2.1. 
Permitted Medications ................................................................................................58 
7.2.2. 
Prohibited Medications and Medications to be Avoided ............................................58 
7.3. 
Treatment Compliance ................................................................................................59 
7.4. 
Randomization and Blinding ......................................................................................59 
8. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................60 
8.1. 
VIC-1911 ....................................................................................................................60 
8.1.1. 
Study Drug Description ..............................................................................................60 
8.1.2. 
Study Drug Packaging and Labeling ..........................................................................60 
8.1.3. 
Study Drug Storage .....................................................................................................60 
8.1.4. 
Administration ............................................................................................................60 
8.2. 
Sotorasib .....................................................................................................................61 
8.2.1. 
Description ..................................................................................................................61 
8.2.2. 
Packaging and Labeling ..............................................................................................61 
8.2.3. 
Storage ........................................................................................................................61 
8.2.4. 
Administration ............................................................................................................61 
8.3. 
Study Drug Accountability .........................................................................................63 
8.4. 
Study Drug Handling and Disposal ............................................................................63 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
15 
November 11, 2022 
 
Amendment 2 
 
 
9. 
STUDY PROCEDURES ............................................................................................64 
9.1. 
Screening Procedures ..................................................................................................64 
9.2. 
Requirements During Treatment Cycle 1 ...................................................................64 
9.2.1. 
Cycle 1, Day 1 ............................................................................................................64 
9.2.2. 
Cycle 1, Day 15 (± 1 day) ...........................................................................................65 
9.3. 
Cycles 2 and 3 (to be performed within 3 days prior to Day 1 of each cycle, 
unless otherwise specified) .........................................................................................66 
9.4. 
Cycle 4 and beyond (To be performed within 3 days prior to Day 1 of each 
cycle, unless otherwise stated) ....................................................................................66 
9.5. 
At Relapse or Progression of Disease .........................................................................67 
9.6. 
End of Treatment (28 Days After Last Dose of VIC-1911 or VIC-1911 Plus 
Sotorasib Study Medication ± 5 days) ........................................................................67 
9.7. 
Long-Term Follow-Up ...............................................................................................68 
10. 
DESCRIPTION OF ASSESSMENTS .......................................................................69 
10.1. 
Safety Assessments .....................................................................................................69 
10.2. 
Safety Parameters .......................................................................................................69 
10.2.1. 
Vital Signs ..................................................................................................................69 
10.2.2. 
Weight and Height ......................................................................................................69 
10.2.3. 
Physical Examination .................................................................................................69 
10.2.4. 
Electrocardiogram (ECG) ...........................................................................................69 
10.2.5. 
Ophthalmologic Tests .................................................................................................69 
10.2.6. 
Laboratory Assessments .............................................................................................70 
10.3. 
Adverse Events and Serious Adverse Events .............................................................70 
10.3.1. 
Definition of Adverse Events .....................................................................................70 
10.3.1.1. 
Adverse Event .............................................................................................................70 
10.3.1.2. 
Serious Adverse Event ................................................................................................71 
10.3.1.3. 
Unexpected Adverse Event .........................................................................................71 
10.3.1.4. 
Adverse Event Reporting Period ................................................................................72 
10.3.1.5. 
Recording of Adverse Events .....................................................................................72 
10.3.1.6. 
Adverse Event Reporting ............................................................................................73 
10.3.1.7. 
Adverse Event and Serious Adverse Event Follow-Up ..............................................74 
10.3.1.8. 
Ongoing Safety Evaluation .........................................................................................74 
10.4. 
Efficacy Assessments .................................................................................................74 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
16 
November 11, 2022 
 
Amendment 2 
 
 
10.4.1. 
Efficacy Endpoints ......................................................................................................75 
10.4.1.1. 
Primary Efficacy Endpoint .........................................................................................75 
10.4.1.2. 
Secondary Efficacy Endpoints ....................................................................................75 
10.4.2. 
Timing of Assessments to Determine Objective Response ........................................75 
10.4.3. 
Timing of ctDNA and Tumor Pharmacodynamic Assessments .................................75 
10.5. 
Pharmacokinetic Assessment ......................................................................................75 
10.6. 
Pharmacodynamic Assessment ...................................................................................76 
11. 
STATISTICAL METHODOLOGY ...........................................................................77 
11.1. 
Determination of Sample Size ....................................................................................77 
11.2. 
Monitoring Guidelines (Early Stopping Rules for Excess Toxicity) ..........................78 
11.3. 
Analysis Populations ..................................................................................................80 
11.4. 
Statistical Analysis Methods.......................................................................................80 
11.4.1. 
Safety Analysis ...........................................................................................................80 
11.4.1.1. 
Adverse Events ...........................................................................................................80 
11.4.1.2. 
Laboratory Data ..........................................................................................................81 
11.4.1.3. 
Vital Signs ..................................................................................................................81 
11.4.1.4. 
Other Safety Data .......................................................................................................81 
11.4.2. 
Efficacy Analysis ........................................................................................................81 
11.4.2.1. 
Primary Efficacy Endpoint .........................................................................................81 
11.4.2.2. 
Secondary Efficacy Endpoints ....................................................................................81 
11.4.3. 
Pharmacokinetic Endpoint Analysis ...........................................................................82 
11.4.4. 
Pharmacodynamic Endpoint Analysis ........................................................................82 
12. 
STUDY MANAGEMENT .........................................................................................83 
12.1. 
Data Management .......................................................................................................83 
12.2. 
Monitoring ..................................................................................................................83 
12.3. 
Audits and Inspections ................................................................................................83 
12.4. 
Amendments ...............................................................................................................83 
12.5. 
Institutional Review Board .........................................................................................84 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................85 
14. 
ETHICS ......................................................................................................................86 
14.1. 
Ethics Review .............................................................................................................86 
14.2. 
Ethical Conduct of the Study ......................................................................................86 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
17 
November 11, 2022 
 
Amendment 2 
 
 
14.3. 
Written Informed Consent ..........................................................................................86 
15. 
DATA HANDLING AND RECORDKEEPING .......................................................87 
15.1. 
Health Insurance Portability Accountability Act of 1996 ..........................................87 
15.2. 
Financial Disclosure ...................................................................................................87 
15.3. 
Inspection of Records .................................................................................................87 
15.4. 
Access to Original Records ........................................................................................87 
15.5. 
Retention of Records ..................................................................................................87 
16. 
LIST OF REFERENCES ............................................................................................88 
APPENDIX A. EASTERN COOPERATIVE GROUP (ECOG) PERFORMANCE 
STATUS SCALE ........................................................................................................91 
APPENDIX B. COCKCROFT-GAULT FORMULA FOR CALCULATION OF 
CREATININE CLEARANCE ....................................................................................92 
APPENDIX C. NEW YORK HEART ASSOCIATION (NYCA) CLASSIFICATION 
FOR HEART FAILURE – THE STAGES OF HEART FAILURE...........................93 
APPENDIX D. SCHEDULE OF STUDY PROCEDURES .......................................................94 
APPENDIX E. RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
(RECIST 1.1)32 ...........................................................................................................97 
APPENDIX F. VIC-1911-01 TUMOR CORRELATIVE ANALYSIS PLAN .........................110 
APPENDIX G. ETHICAL STANDARDS ...............................................................................112 
 
LIST OF TABLES 
Table 1: Abbreviations and Specialist Terms ................................................................................19 
Table 2: VIC-1911 IC50 Values Against Aurora Kinases A, B and C ...........................................24 
Table 3: VIC-1911 IC50s for AurA Kinase and AurB Kinase in HeLa and NCI- H460 
Cells ............................................................................................................................25 
Table 4:VIC-1911 Cell Line Sensitivity: Gene Abnormality Status of MYC Amplification .........26 
Table 5: VIC-1911 IC50s in Human Cancer Cell Lines vs. Other Aurora Kinase 
Inhibitors .....................................................................................................................27 
Table 6: IC50s (nM) for VIC-1911 and Osimertinib Against Osimertinib-Resistant 
NSCLC Human Cancer Cell Lines .............................................................................28 
Table 7: VIC-1911 Monotherapy Dose Escalation Levels ............................................................43 
Table 8: Combination VIC-1911 Plus Sotorasib Dose Escalation Levels .....................................44 
Table 9: VIC-1911 Dose Modification Guidelines ........................................................................50 
Table 10: Sotorasib (LUMAKRAS) Dose Reduction Guidelines23 ..............................................50 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
18 
November 11, 2022 
 
Amendment 2 
 
 
Table 11: Sotorasib (LUMAKRAS) Dose Modification Guidelines23 ..........................................51 
Table 12: Clinical Laboratory Parameters .....................................................................................70 
Table 13: Reporting Guidelines for Adverse Events .....................................................................73 
 
LIST OF FIGURES 
Figure 1: Accumulation of Phospho-histone H3 in VIC-1911 (TAS-119) Treated HeLa 
Cells (A) and NCI-H460 cells (B) ..............................................................................25 
Figure 2: Activity of VIC-1911 Plus Sotorasib Against Intrinsic Resistance to KRAS 
G12C-Mutant NSCLC Human Cell Lines ..................................................................28 
Figure 3: Activity of VIC-1911 Plus Sotorasib Against Acquired Resistance to KRAS 
G12-C-Mutant NSCLC Human Cell Line NCI-H358 ................................................29 
Figure 4: Anti-tumor Efficacy of VIC-1911 (formerly TAS-119.Na) Against A427 
Human Lung Carcinoma Xenografts in a Nude Mouse Model ..................................30 
Figure 5: Anti-tumor Efficacy of VIC-1911 or LY3295668 Against NCI-H69 Human 
SCLC in a Nude Mouse Xenograft Model .................................................................31 
Figure 6: Anti-tumor Efficacy of VIC-1911 Plus Osimertinib Against NCI-H1975-OR 
Human NSCLC in a Nude Mouse Xenograft Model ..................................................31 
Figure 7: Synergistic Activity of VIC-1911 and Sotorasib Combination Treatment in 
KRAS G12C-Mutant Human Cell Line NCI-H358 ....................................................32 
Figure 8: Synergistic Activity of VIC-1911 and Sotorasib Combination Treatment in 
NSCLC KRAS G12C-Mutant PDX Xenograft Model ...............................................32 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
19 
November 11, 2022 
 
Amendment 2 
 
 
2. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
AE 
Adverse event 
AKT 
Protein kinase B 
ALT 
Alanine transaminase 
ANC 
Absolute neutrophil count 
APTT 
Activated partial thromboplastin time 
AST 
Aspartate transaminase 
AUC 
Area under the concentration-time curve (exposure) 
AurA 
Aurora A 
AurB 
Aurora B 
AurC 
Aurora C 
BCRP 
Breast cancer resistance protein 
b.i.d. 
Twice daily 
BRAF, B-Raf 
BRAF is the human proto-oncogene that encodes the 
serine/threonine-protein kinase B-Raf 
BUN 
Blood urea nitrogen 
C 
Centigrade 
Cmax 
Maximum plasma concentration 
CLIA 
Clinical Laboratory Improvement Amendments 
CR 
Complete response 
CT 
Computed tomography 
ctDNA 
Circulating tumor DNA 
CTCAE 
Common terminology criteria for adverse events 
CYP 
Cytochrome P450 
DCR 
Disease control rate 
DDI 
Drug-drug interaction 
DLT 
Dose limiting toxicity 
DoR 
Duration of response 
ECG 
Electrocardiogram 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
20 
November 11, 2022 
 
Amendment 2 
 
 
Abbreviation or Specialist Term 
Explanation 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
ED50 
Concentration for 50% effectiveness 
EDTA 
Ethylenediaminetetraacetic acid 
EGFR 
Epidermal growth factor receptor 
ERK 
Extracellular signal-regulated kinase 
F 
Bioavailability 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
GALT 
Gut-associated lymphoid tissue 
G protein 
guanine nucleotide-binding proteins 
GCP 
Good Clinical Practice 
G-CSF 
Granulocyte colony-stimulating factor 
GDP 
Guanosine diphosphate 
GI 
Gastrointestinal 
GLP 
Good Laboratory Practice 
GM-CSF 
Granulocyte-macrophage colony-stimulating factor 
GPT 
Guanosine triphosphate 
GVHD 
Graft versus host disease 
Hb 
Hemoglobin 
HBV 
Hepatitis B virus 
HCG 
Human chorionic gonadotropin 
HCV 
Hepatitis C virus 
HDPE 
High density polypropylene 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
HNSTD 
Highest non-severely toxic dose 
HSCT 
Hematopoietic stem cell transplantation 
HRAS 
Harvey RAS 
IC50 
Concentration for 50% maximal inhibition 
ICD 
Informed consent document 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
21 
November 11, 2022 
 
Amendment 2 
 
 
Abbreviation or Specialist Term 
Explanation 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
ILD 
Interstitial lung disease 
IND 
Investigational New Drug 
IOP 
Intraocular pressure 
IV 
Intravenous 
IRB 
Institutional Review Board 
Kg 
Kilogram 
Ki 
Inhibition constant 
Kinact 
Rate of inactivation 
Km 
Binding affinity or Michaelis-Menten constant 
KRAS 
Kirsten RAS 
L 
Liter 
LDH 
Lactate dehydrogenase 
LFT 
Liver function test 
LOF 
Loss of function 
MDR1 
Multidrug resistance protein 1 
MedDRA 
Medical Dictionary for Regulatory Activities 
MEK 
Mitogen-activated protein kinase kinase 
Mg 
Milligram 
mL 
Milliliter 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
mTORC1 
Mammalian target of rapamycin complex 1 
NCI 
National Cancer Institute 
nM 
Nanomolar 
NOAEL 
No adverse effect level 
NRAS 
Neuroblastoma rat sarcoma 
NSCLC 
Non-small cell lung cancer 
NYHA 
New York Heart Association 
OCT 
Optical coherence tomography 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
22 
November 11, 2022 
 
Amendment 2 
 
 
Abbreviation or Specialist Term 
Explanation 
OR 
Objective response 
ORR 
Objective response rate 
OS 
Overall survival 
PD 
Progressive disease 
PD-1 
Programmed death protein 1 
PD-L1 
Programmed death ligand 1 
PFS 
Progression-free survival 
P-gp 
P-glycoprotein 
pHH3 
Phospho-histone H3 
PI 
Principal Investigator 
PI3K 
Phosphoinositide 3-kinase 
PK 
Pharmacokinetic 
PO 
Per os (oral) 
PPS 
Per protocol set 
PR 
Partial response 
PT (INR) 
Prothrombin time (international normalized ratio) 
PTX 
Paclitaxel 
q.d. 
Once daily 
q.o.d. 
Every other day 
QTc 
QT interval corrected for rate 
RAF 
Rapidly accelerated fibrosarcoma 
RAL/RALGDS 
Ras-like/Ral guanine nucleotide dissociation stimulator 
RAS 
Rat sarcoma  
RASA1 
Gene encoding RAS-GAP activating protein 
RAS-GAP 
RAS oncogene GTP-ase activating protein 
RBC 
Red blood cell 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RET 
Ret proto-oncogene 
ROS 
Proto-oncogene encoding receptor tyrosine kinase protein 
RP2D 
Recommended Phase 2 dose 
SAE 
Serious adverse event 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
23 
November 11, 2022 
 
Amendment 2 
 
 
Abbreviation or Specialist Term 
Explanation 
SCLC 
Small cell lung cancer 
SD 
Stable disease 
SRC 
Safety Review Committee 
STD10 
Severely toxic dose in 10% of animals 
T1/2  
Half-life 
Tmax 
Time to maximum plasma concentration 
T/C 
Tumor growth inhibition ratio 
TEAE 
Treatment-emergent adverse event 
TGD 
Tumor growth delay 
TK 
Toxicokinetic 
TRKA 
Tropomyosin receptor kinase A 
TRKB 
Tropomyosin receptor kinase B 
TRKC 
Tropomyosin receptor kinase C 
UGT 
Uridine 5’-diphospho (UDP)-glucuronosyltranferase 
ULN 
Upper limit of normal 
Vd 
Volume of distribution 
WCBP 
Woman of child-bearing potential 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
24 
November 11, 2022 
 
Amendment 2 
 
 
3. 
INTRODUCTION 
3.1. 
VIC-1911 Summary  
VIC-1911 is a novel, selective, and orally active small molecular inhibitor of Aurora A (AurA) 
kinase under development for the treatment of solid tumors, hematologic malignancies and the 
prevention of acute graft versus host disease (GVHD) following hematopoietic stem cell 
transplantation (HSCT). AurA kinase, a key regulator in mitotic cell division, is associated with 
spindle assembly checkpoint and regulation of the transition from G2 to M phase.1 AurA gene 
amplification and/or overexpression are reported in various tumor types, including breast, lung, 
gastro-esophageal, bladder, ovary, prostate, pancreas and hematologic malignancies.2,3,4,5 
Overexpression of AurA kinase also is associated with disease progression and survival in various 
cancers.6,7,8,9 Elevated levels of AurA kinase are reported to override the mitotic spindle 
checkpoint activated by treatment with chemotherapeutic agents like taxanes, and are linked to 
taxane resistance.10,11 
VIC-1911 has demonstrated activity in nonclinical studies at concentrations and doses which have 
been shown to selectively inhibit AurA, a pharmacokinetic profile supportive of twice daily 
administration with either a daily b.i.d. continuous 28-day cycle or a Day 1-4, 8-11, 15-18 b.i.d. 
intermittent 28-day cycle. An acceptable safety profile was demonstrated in nonclinical (both 
continuous and intermittent regimens) and clinical studies (intermittent regimen), including 
combination treatment with paclitaxel and docetaxel. Additional information is found in the VIC-
1911 Investigator’s Brochure.12 
3.1.1. 
Preclinical Pharmacology  
3.1.1.1. 
In Vitro 
VIC-1911 selectively inhibited human recombinant AurA kinase (half maximal inhibitory 
concentration [IC50] 1.04 nM) versus Aurora B (AurB) kinase (IC50 95 nM) or Aurora C (AurC) 
kinase (IC50 36.5 nM), with 91- and 35-fold higher selectively, respectively, for AurA (Table 2).  
Table 2: VIC-1911 IC50 Values Against Aurora Kinases A, B and C 
Aurora Kinase 
AurA* 
AurB 
AurC 
IC50 (nM) 
1.04 ± 0.09 
95 ± 11 
36.5 ± 6.2 
 
 
 
 
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
25 
November 11, 2022 
 
Amendment 2 
 
 
VIC-1911 inhibited AurA kinase autophosphorylation in cervical cancer HeLa (IC50: 13.9 nM) 
and non-small cell cancer (NSCLC) NCI-H460 cells (IC50:13.7 nM) showing selectivity for AurA 
over AurB of > 720-fold in HeLa cells and > 730-fold in NCI-H460 cells (Table 3). 
Table 3: VIC-1911 IC50s for AurA Kinase and AurB Kinase in HeLa and NCI- H460 Cells 
Cell Line 
IC50 (pAurA) 
IC50 (pAurB) 
Ratio* 
HeLa 
13.9 
>10000 
>720 
NCI-H460 
13.7 
>10000 
>730 
*Ratio of the IC50 (i.e., IC50 AurB  / IC50 AurA) 
VIC-1911 showed no significant inhibition against a panel of 301 other human protein kinases 
except for recombinant human Ret proto-oncogene (RET) (S891A) (IC50 25.8 nM), proto-
oncogene tyrosine protein kinase ROS (ROS) (IC50 29.3 nM), tropomyosin receptor kinase A 
(TRKA) (IC50 1.46 nM), tropomyosin receptor kinase B (TRKB) (IC50 1.53 nM) and tropomyosin 
receptor kinase C (TRKC) (IC50 1.47 nM).  
Incubation of both HeLa and NCI-H460 cells with VIC-1911 dose-dependently increased the 
number of phosphorylated histone H3 (pHH3)-positive cells (a selective marker of AurA 
inhibition) with ED50 values of 105.8 and 132.1 nM, in HeLa and H460 cells, respectively (Figure 
1). VIC-1911 also induced the accumulation of pHH3-positive cells in both OCUM- 2M and 
MDA-MB-231 cells (data not shown).  
Figure 1: Accumulation of Phospho-histone H3 in VIC-1911 (TAS-119) Treated HeLa Cells 
(A) and NCI-H460 cells (B) 
(A)  
 
 
 
(B) 
 
In a 240 human tumor cell line study, VIC-1911 inhibited cell growth, with most potency (IC50) 
demonstrated against lung NCI-H69 (14 nM), neuroblastoma IMR-32 (14 nM) and colon SW48 
(18.9 nM). Among the 10 most sensitive cell lines, 4 possessed MYC amplification (N- myc or c-
myc) and 4 other cell lines showed CTNNB1 (β-catenin) mutation (Table 4).  
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
26 
November 11, 2022 
 
Amendment 2 
 
 
Table 4:VIC-1911 Cell Line Sensitivity: Gene Abnormality Status of MYC Amplification  
and CTNNB1 Mutation  
Rank Orde r 
Ce ll line 
IC50 (μmol/L) 
CTNNB1 
MYC 
Tumor Type 
1 
NCI-H69 
0.014 
wt  
N-myc amp 
Lung 
2 
IMR-32 
0.014 
wt 
N-myc amp 
Neuroblastoma 
3 
SW48 
0.0189 
mut 
wt 
Colon 
4 
AGS 
0.0204 
mut 
wt 
Stomach 
5 
CHP-212 
0.0262 
wt 
N-myc amp 
Neuroblastoma 
6 
HCT-116 
0.0265 
mut 
wt 
Colon 
7 
SW-13 
0.0269 
wt 
wt 
Endocrine 
8 
MC-IXC 
0.0274 
wt 
c-myc amp 
Neuroblastoma 
9 
CRO-AP2 
0.0287 
wt 
wt 
Hematopoietic 
10 
A427 
0.0291 
mut 
wt 
Lung 
11 
MDA MB 
453 
0.0304 
wt 
wt 
Breast 
12 
KPL-1 
0.0327 
wt 
wt 
Breast 
13 
CEM-C1 
0.0337 
unknown 
unknown 
Hematopoietic 
14 
SR 
0.0343 
wt 
wt 
Hematopoietic 
15 
Daoy 
0.0349 
wt 
wt 
CNS 
16 
G-401 
0.0363 
wt 
wt 
Kidney 
17 
BeWo 
0.0378 
unknown 
unknown 
Placenta 
18 
CAMA-1 
0.0384 
wt 
wt 
Breast 
19 
KHOS-240S 
0.0396 
unknown 
unknown 
Soft Tissue 
20 
NCI-H520 
0.0432 
wt 
L-myc amp 
Lung 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
27 
November 11, 2022 
 
Amendment 2 
 
 
VIC-1911 exhibited nM potency against an additional 12 human cancer cell lines, 9 with Rb LOF 
mutation, reported to be more sensitive to AurA kinase inhibition. Specific AurA kinase inhibitors 
VIC-1911 and LY3295668 showed similar potency against all cell lines tested, different from 
AurB kinase inhibitor, barasertib, and AurA kinase selective inhibitor, alisertib (Table 5). 
Table 5: VIC-1911 IC50s in Human Cancer Cell Lines vs. Other Aurora Kinase Inhibitors 
Cell Line 
Tumor Type 
Compound (IC50. nM) 
 
 
Control 
Barasertiba 
Alisertibb 
LY3295668c 
VIC-1911c 
NCI-H524 
SCLC 
447 
2.7 
9.6 
19.8 
6.1 
DU-4475 
Breast 
15.7 
21.3 
13.9 
86.1 
39.4 
NCI-H446 
SCLC 
10,000 
8.7 
1.5 
12.1 
3.8 
NCI-H82 
SCLC 
1858 
1.2 
2.6 
17.9 
24.8 
U-266 
Plasma cell 
myeloma 
354 
10,000 
8.2 
44.7 
26.1 
NCI-H69 
SCLC 
1535 
19.1 
6.6 
16.1 
5.3 
NCI-H1734 
NSCLC 
242 
224 
15.1 
45.5 
61.8 
SW48 
Large 
Intestine 
14.0 
2.3 
0.3 
6.3 
3.6 
HCT-116 
Large 
Intestine 
63.0 
10,000 
0.4 
8.3 
26.7 
MDA-
MB468 
Breast 
(TNBC) 
34.8 
5,531 
0.8 
7.9 
7.0 
MDA-
MB231 
Breast 
(TNBC) 
164 
3964 
1953 
23.2 
26.8 
NSCLC = non-small cell lung cancer 
SCLC = small cell lung cancer 
TNBC = triple negative breast cancer 
a AurB kinase inhibitor 
b Selective AurA kinase inhibitor 
c Specific AurA kinase inhibitor 
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
28 
November 11, 2022 
 
Amendment 2 
 
 
VIC-1911 enhanced the antiproliferative effect in osimertinib-acquired resistant cells, and VIC-
1911 plus osimertinib treatment enhanced the magnitude of the response in osimertinib-resistant 
cells (Table 6). 
Table 6: IC50s (nM) for VIC-1911 and Osimertinib Against Osimertinib-Resistant NSCLC 
Human Cancer Cell Lines 
 
IC50 (nM) 
Drug 
NCI-H1975 
NCI-1975-OR 
HCC827 
HCC827-OR 
VIC-1911 
38 
81 
192 
219 
Osimertinib 
7 
2589 
5.8 
5097 
OR = Osimertinib-resistant 
Combination VIC-1911 and sotorasib demonstrated synergy in KRAS G12C-mutated NSCLC cell 
lines with intrinsic and acquired sotorasib resistance (Figure 2 and  
Figure 3).13 
Figure 2: Activity of VIC-1911 Plus Sotorasib Against Intrinsic Resistance to KRAS G12C-
Mutant NSCLC Human Cell Lines 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
29 
November 11, 2022 
 
Amendment 2 
 
 
 
Figure 3: Activity of VIC-1911 Plus Sotorasib Against Acquired Resistance to KRAS G12-
C-Mutant NSCLC Human Cell Line NCI-H358 
 
3.1.1.2. 
In Vivo 
In athymic nude mice bearing human NSCLC KRAS-mutant A427 cell line xenografts, VIC-1911 
(100 mg/kg PO, b.i.d. x 4 days starting on D1 and D8) demonstrated maximum tumor growth delay 
(TGD) and overall survival benefit (p<0.006) vs. lower doses of 60 mg/kg PO, b.i.d. continuously 
for 14 days and 60 mg/kg p.o, b.i.d. x 4 days starting on D1 and D8. Evaluation of maximum tumor 
volume at D15 showed VIC-1911 (60 mg/kg PO, b.i.d x 14 days) significantly reduced tumor 
volume versus vehicle control (T/C; 21%) (p<0.01). VIC-1911 (60 mg/kg and 100 mg/kg) 
administered intermittently (cycled PO, b.i.d. x 4 days) was also efficacious with T/C; 30% and 
20% respectively (p<0.001). Positive control paclitaxel (PTX) (30 mg/kg IV, every other day 
[q.o.d.] x5), was efficacious, resulting in maximum TGD, 100% regression and a significant 
survival benefit compared to vehicle control (p<0.001) (Figure 4). 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
30 
November 11, 2022 
 
Amendment 2 
 
 
Figure 4: Anti-tumor Efficacy of VIC-1911 (formerly TAS-119.Na) Against A427 Human 
Lung Carcinoma Xenografts in a Nude Mouse Model 
 
 
The growth of small cell lung cancer (SCLC) NCI-H69 lung cancer xenografts was inhibited by 
treatment with AurA kinase inhibitors LY3295668 or VIC-1911. Continuous dosing of VIC-1911 
demonstrated more potent anti-tumor effect, with further reduction in tumor volume and longer 
time to tumor regrowth compared to the intermittent VIC-1911 dosing (p<0.0001 for all VIC-1911 
and LY3295668 dose groups versus vehicle control) (Figure 5).  
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
31 
November 11, 2022 
 
Amendment 2 
 
 
Figure 5: Anti-tumor Efficacy of VIC-1911 or LY3295668 Against NCI-H69 Human SCLC 
in a Nude Mouse Xenograft Model 
 
 In athymic nude mice bearing NSCLC NCI-H1975 osimertinib-resistant xenografts with VIC-
1911 (30 mg/kg b.i.d.) plus osimertinib (1 or 5 mg/kg q.d.) daily for 30 days demonstrated more 
potent antitumor effects and kept the tumors from regrowth for longer duration than VIC-1911 or 
osimertinib treatment alone (p<0.001) (Figure 6). 
Figure 6: Anti-tumor Efficacy of VIC-1911 Plus Osimertinib Against NCI-H1975-OR 
Human NSCLC in a Nude Mouse Xenograft Model 
 
VITRAC in-house preclinical studies demonstrated synergy with VIC-1911 and sotorasib on a 
continuous dosing schedule compared with their respective monotherapies in KRAS G12C-
mutated NSCLC xenograft models, NCI-H358 (Figure 7).14 VIC-1911 also demonstrated synergy 
with sotorasib on a continuous dosing schedule in a KRAS G12C-mutant patient-derived xenograft 
 
 
Dosing day 1-30 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
32 
November 11, 2022 
 
Amendment 2 
 
 
(PDX) model (LU-01-0030) (Figure 8).15 These findings suggest that combination VIC-1911 and 
sotorasib may be more active than sotorasib and VIC-1911 alone in KRAS G12C-mutated NSCLC 
that is naïve to G12C inhibitors.  
Figure 7: Synergistic Activity of VIC-1911 and Sotorasib Combination Treatment in KRAS 
G12C-Mutant Human Cell Line NCI-H358   
 
 
Figure 8: Synergistic Activity of VIC-1911 and Sotorasib Combination Treatment in 
NSCLC KRAS G12C-Mutant PDX Xenograft Model  
 
 
 
Safety pharmacology core battery studies showed that VIC-1911 had little to no effect on 
behavioral or physiological functions. Repeat daily dosing of VIC-1911 had no effect on 
cardiovascular function.  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
33 
November 11, 2022 
 
Amendment 2 
 
 
3.1.2. 
Preclinical Pharmacokinetics  
Nonclinical pharmacokinetic (PK) profiles of VIC-1911 have been characterized in rats and dogs 
in single-dose and repeat-dose studies after IV and p.o. administrations. Absorption of VIC-1911 
after oral dosing occurred rapidly in all species studied at doses up to 112 mg/kg b.i.d. with time 
to maximum plasma concentration (Tmax) 0.5 – 4.0 hours post-dose in rat and dog.  
Following repeat oral administration of VIC-1911 to the rat over the dose range 21-84 mg/kg/b.i.d. 
for durations up to 3 weeks (cyclical dosing, with 4 days dosing and 3 days off dosing per week), 
mean exposure to VIC-1911 was broadly dose proportional or greater than dose proportional 
(particularly at higher doses). VIC-1911 was rapidly absorbed after oral dosing to rats, and 
maximum concentrations (Cmax) was 0.5 – 1.0 hours post-dose (Tmax). 
Following a single oral gavage administration of VIC-1911 to dogs over the dose range 28-112 
mg/kg, rapid drug absorption was seen at all dose levels, however, there was no obvious trend in 
increased exposure with increasing dose level.  For example, dogs given a single dose at 42 mg/kg 
had plasma exposure substantially higher than those dosed at 56 mg/kg. b.i.d. Following repeated 
cyclical dosing, with 4 days dosing and 3 days off dosing per week, or 28-42 mg/kg b.i.d. 
(continuous dosing) for durations up to 3 weeks, exposure was, in general, of the same order of 
magnitude compared with that following a single administration. Exposures in males and females 
were broadly similar after gavage dosing, although individual variability was observed. There was 
little evidence of accumulation of VIC-1911 with repeated administration. 
In vitro investigations indicated that VIC-1911 is highly bound to plasma proteins in rat (98%), 
dog (94%) and human (99.4%). There was no evidence of saturation of protein binding over the 
concentration range 1-20 µM in plasma from all species and human plasma fractions. VIC-1911 
had low distribution to human blood cells in vitro. 
In vitro studies indicated that VIC-1911 is a substrate of human multidrug resistance protein 1 
(MDR1), but not breast cancer resistance protein (BCRP), and is not an inhibitor of either 
transporter. In addition, VIC-1911 is a substrate of OATP1B1 and OATP1B3, but not of OCT1. 
The Km of VIC-1911 for OATP1B1 is 0.6 µmol/L. The OATP1B1-mediated uptake of VIC-1911 
was inhibited by PTX and DTX. Although VIC-1911 inhibited the OATP1B1 and OATP1B3-
mediated transport of PTX and DTX, the impact of VIC-1911 on plasma levels of PTX and DTX 
was predicted to be low due to their high passive membrane permeability. 
In vitro incubations of VIC-1911 in human, rat and dog hepatocytes indicated a single major 
metabolite in all three species. Analysis of this component characterized it as the acyl glucuronide 
of VIC-1911. 
After oral dosing of radiolabeled VIC-1911 to rats, drug-related radioactivity was excreted 
primarily in the feces with 97.4% of the dose recovered by 72 hours, with < 1% recovered in urine. 
No quantifiable radioactivity was detected by 72 hours after dosing. In bile duct-cannulated rats, 
57.6% of administered radioactivity was excreted in bile after oral dosing. 
In vitro studies with human liver microsomes have shown that VIC-1911 has the potential to inhibit 
CYPP2C8 (IC50 = 25 µM) and CP3A4/5 (IC50 = 180 µM) including metabolism-dependent 
inhibition (CYP2C8 IC50 = 14 µM; CYP3A4/5 (IC50 = 72 µM). Human hepatocyte studies 
demonstrated VIC-1911 has induction potential for CYP3A4 at a concentration of 10 µM. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
34 
November 11, 2022 
 
Amendment 2 
 
 
3.1.3. 
Preclinical Toxicology 
AurA kinase regulates the correct development of the various phases of mitosis, and in humans is 
expressed at detectable levels in all somatic cells undergoing mitotic cell division. VIC-1911 acts 
to reduce or block AurA kinase activity and therefore prevent normal cell cycling at mitosis. 
Aberrations of the mitotic processes make it possible for apoptosis or single cell necrosis to occur. 
The treatment-related histopathological findings observed in these studies (widespread lymphoid 
atrophy and epithelial cell degeneration/regeneration) could therefore be directly or indirectly 
associated with the pharmacological effects of VIC-1911 in disruption of the mitotic process. 
In the rat, following VIC-1911 cyclical dosing (4 days on followed by 3 days off) for 3 cycles, or 
daily b.i.d. dosing for 21 days continuously, the severely toxic dose in 10% of the animals (STD10) 
was 63 mg/kg b.i.d. Major findings included body weight loss, reduced food consumption, 
reduction in hemoglobin, red blood cell (RBC) counts, packed cell volume and reticulocytes, 
elevated liver enzymes, total bilirubin and decreased albumin, degeneration and regeneration or 
hyperplasia of epithelial tissue (liver, eye, skin, tongue, esophagus, pancreas, parotid salivary 
gland, GI tract, adrenal, kidney, lung and heart), atrophy of lymphoid and/or hemopoietic tissues 
(bone marrow, spleen, thymus, GALT/Peyer’s patch, mesenteric and popliteal lymph nodes) and 
generally atrophic findings in reproductive tissues (testis, epididymis, seminal vesicle, prostate, 
ovary and uterus). These findings showed evidence of reversibility during the 2-week recovery 
period. 
In the dog, following VIC-1911 cyclical dosing (4 days on followed by 3 days off) for 3 cycles, or 
daily b.i.d. dosing for 21 days continuously, the highest non-severely toxic dose (HNSTD) was > 
84 mg/kg b.i.d. Major findings included vomiting, diarrhea, decreased food consumption, body 
weight loss, elevated liver enzymes, total bilirubin, widespread lymphoid atrophy, scattered 
individual epithelial cell degeneration/regeneration in a range of tissues, mucosal 
atrophy/inflammation in the gut and pyloric gastritis, bile duct hyperplasia/inflammation in liver 
and gall bladder inflammation, right atrial epicarditis and myocarditis, pulmonary alveolitis and 
minor metaphyseal congestion/trabecular atrophy in bone. These findings showed evidence of 
reversibility during the 2-week recovery period. 
The no adverse effect level (NOAEL) in rat and dog was 21 and 28 mg/kg b.i.d., respectively.  
VIC-1911 was not phototoxic. No genotoxicity or specific reproductive or developmental 
toxicology studies have been conducted.  
3.2. 
Rationale for Targeting RAS Mutations in NSCLC 
Lung cancer is the leading cause of cancer death in the United States.16 In the US, 228,820 new 
cases and 135,720 deaths were projected for lung cancer in 2020.16  
Rat Sarcoma (RAS) is the most commonly mutated gene in human malignancies, including 
NSCLC.17,18 RAS genes encode a family of small, membrane-bound, guanine nucleotide-binding 
proteins (G proteins), including Kirsten RAS (KRAS), neuroblastoma RAS (NRAS), and Harvey 
RAS (HRAS). KRAS mutation is the most common RAS gene mutation, accounting for 
approximately 80% of RAS mutations.19 RAS proteins are binary switches that cycle between an 
active guanosine triphosphate (GTP)-bound conformation and an inactive guanosine diphosphate 
(GDP)-bound conformation.17 GTP-bound RAS activates multiple downstream effector protein 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
35 
November 11, 2022 
 
Amendment 2 
 
 
pathways, including rapidly accelerated fibrosarcoma/ mitogen-activated protein kinase 
kinase/extracellular signal-regulated kinase (RAF/MEK/ERK), phosphoinositide 3-kinase/protein 
kinase B/mammalian target of rapamycin complex 1 (PI3K/AKT/mTORC1), and Ras-like/Ral 
guanine nucleotide dissociation stimulator (RAL/RALGDS). RAS mutations stabilize or “lock in” 
the active, GTP-bound mutant protein. These constitutively active GTP-bound mutant RAS 
proteins continuously activate downstream signaling and lead to uncontrolled cell proliferation 
and survival. As a result, RAS mutations are oncogenic drivers. KRAS gene mutations can occur at 
codon 12 due to a single point mutation with a glycine-to-cysteine substitution (KRAS G12C). In 
Western populations, approximately one-quarter to one-third of patients with NSCLC have a KRAS 
mutation.17 KRAS G12C mutations occur in  12%-16% of patients with NSCLC (approximately 
40% of all KRAS mutations).17,18 NSCLC with KRAS G12C mutations represents diseases with a 
poor prognosis.17,20,21 
Recently, a new class of KRAS G12C small molecule kinase inhibitors have been successfully 
developed.20,22 Sotorasib is the most advanced of these KRAS G12C inhibitors. Sotorasib is a 
highly selective, irreversible, oral inhibitor composed of a pyridine ring with two conformations 
that produce up to 25 covalent interactions with cysteine 12 in the KRAS G12C mutant 
protein.17,20,22 Sotorasib inhibition occurs by irreversibly locking the KRAS G12C protein in its 
inactive GDP-bound state, thus preventing its oncogenic activity. In preclinical studies, sotorasib 
inhibited KRAS signaling and impaired viability of KRAS G12C-mutated cell lines.  
Sotorasib received FDA accelerated approval in May 202123 based on results of the single-group, 
open-label, phase 2 CodeBreaK100 trial.24 In this trial, sotorasib was administered at a dose of 960 
mg orally once daily in 124 evaluable patients with KRAS G12C-mutated, locally advanced or 
metastatic NSCLC with disease progression after receiving standard first-line therapy. The 
majority (81%) of patients had previously received both platinum-based chemotherapy and 
inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1). The objective 
response rate was 37%, the median duration of response 11.1 months, the median progression-free 
survival 6.8 months, and the median overall survival 12.5 months. The most common adverse 
events (occurring in ≥ 20% of patients) were diarrhea, nausea, fatigue, arthralgia, and increases in 
aspartate or alanine aminotransferase levels. Sotorasib is now FDA indicated for the treatment of 
adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer, 
as determined by an FDA-approved test, who have received at least one prior systemic therapy. 
This indication was obtained under accelerated approval based on ORR and DOR.23 
While sotorasib monotherapy has been rightfully heralded as a significant breakthrough with an 
objective response rate of 37%, still nearly two-thirds of patients have intrinsic resistance to 
sotorasib and most responding patients will develop acquired resistance after approximately 12 
months.18 Thus, new therapeutic strategies are required to overcome intrinsic/de novo and acquired 
resistance to sotorasib.17 
3.3. 
Rationale for Targeting AURA Kinase in NSCLC 
AURA kinase is a key mitotic cell cycle regulator and is associated with spindle assembly 
checkpoint and regulation of the transition from G2 to M phase.1 AURA kinase gene amplification 
and/or overexpression are reported in multiple tumor types, including NSCLC.2,4 AURA kinase 
has been shown to be a mediator of intrinsic and acquired resistance to KRAS G12C inhibitors, 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
36 
November 11, 2022 
 
Amendment 2 
 
 
such as sotorasib, in G12C-mutated NSCLC.13,17,24,25 Augmented upstream AURA kinase 
signaling maintains or stabilizes the mutant KRAS G12C protein in an inhibitor-insensitive state, 
possibly by AURA kinase complexing with the mutant KRAS G12C protein. This complex then 
facilitates the interaction between mutated KRAS G12C protein and downstream CRAF protein.25 
This interaction induces cell-cycle progression and cell proliferation. Therefore, AURA kinase 
inhibition may disrupt these interactions between AURA kinase, mutant KRAS G12C and 
CRAF.19  
Preclinical studies have evaluated the impact of AURA kinase inhibition on intrinsic and acquired 
resistance to KRAS G12C inhibitors, such as sotorasib.13,25 AURA kinase expression was found 
to be increased in KRAS G12C-mutated NSCLC cells resistant to G12C inhibitors, including 
sotorasib.13,25 Combination AURA kinase and KRAS G12C inhibitors showed synergistic in vitro 
antiproliferative and in vivo antitumor effects in KRAS G12C-mutant models with acquired 
resistance to the G12C inhibitor.25 This confirmed the dependence of KRAS G12C inhibitor 
acquired resistance on AURA kinase and suggested that the addition of AURA kinase inhibition 
could overcome acquired resistance to G12C inhibition. 
As noted above, VIC-1911 is a highly selective, small molecular inhibitor of AURA kinase. AURA 
kinase inhibition with VIC-1911 demonstrated monotherapy activity in KRAS G12C-mutated 
human NSCLC cells with intrinsic and acquired resistance to the G12C inhibitor sotorasib, and 
combination VIC-1911 and sotorasib showed synergy in KRAS G12C-mutated NSCLC cell lines 
with intrinsic and acquired sotorasib resistance (Figure 2 and  
Figure 3).13 Interestingly, NSCLC cells with intrinsic resistance to sotorasib showed the most 
profound synergistic effects with the combination of VIC-1911 and sotorasib. These findings 
suggested that 1) AURA kinase activation led to both intrinsic and acquired resistance to sotorasib 
in KRAS G12C-mutated NSCLC and 2) the addition of VIC-1911 AURA kinase inhibition with 
sotorasib may be a potential therapeutic approach for intrinsic and acquired resistance to sotorasib.  
Additionally, VITRAC in-house preclinical studies showed synergy with VIC-1911 and sotorasib 
compared with their respective monotherapies in KRAS G12C-mutated NSCLC xenograft models, 
NCI-H358 (Figure 7) and in a KRAS G12C-mutated PDX) model (LU-01-0030) (Figure 8).15 
These findings suggest that combination VIC-1911 and sotorasib may be more active than 
sotorasib alone in KRAS G12C-mutated NSCLC that is naïve to G12C inhibitors.  
New therapeutic strategies are needed to overcome intrinsic and acquired sotorasib (KRAS G12C 
inhibitor) resistance, especially due to increased AURA kinase activity.13,17,25,26 Preclinical 
mechanistic and therapeutic studies suggest that the combination of VIC-1911 AURA kinase 
inhibition and sotorasib KRAS G12C inhibition may be a promising therapeutic approach in 
sotorasib resistant KRAS G12C mutated NSCLC.13,25 This combination may potentially overcome 
or delay sotorasib primary resistance and overcome sotorasib acquired resistance. In addition, 
preclinical studies suggest that VIC-1911 monotherapy may be a potential therapeutic approach in 
sotorasib resistant NSCLC and could be compared with the combination of VIC-1911 and 
sotorasib.13 Finally, preclinical synergy results support the combination of VIC-1911 AURA 
kinase inhibition and sotorasib KRAS G12C inhibition in sotorasib (G12C inhibitor) naive KRAS 
G12C-mutated NSCLC.13,25 This combination may potentially provide superior results to sotorasib 
alone based on these studies. This provides sufficient rationale to evaluate VIC-1911 monotherapy 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
37 
November 11, 2022 
 
Amendment 2 
 
 
and combination VIC-1911 plus sotorasib in patients with sotorasib intrinsic and acquired 
resistance and combination VIC-1911 plus sotorasib in KRAS G12C-mutated NSCLC naïve to 
sotorasib (KRAS G12C inhibitor) therapy, as proposed in this Phase 1a/1b study.  
3.4. 
Possible Risks and Side Effects 
3.4.1. 
VIC-1911 Monotherapy Phase 1 Study in Advanced Solid Tumors 
A Phase 1, open-label, non-randomized, dose-escalation study of VIC-1911 was conducted 
evaluating the safety, tolerability, PK, pharmacodynamics, pharmacogenomics and preliminary 
anti-tumor activity in patients with advanced, unresectable solid tumors.27 The study consisted of 
two phases, a Dose Escalation Phase to determine the maximum tolerated dose (MTD) and 
recommended Phase 2 dose (RP2D) of VIC-1911 given orally (PO) b.i.d., and an Expansion Phase, 
with VIC-1911 at the RP2D. In the Dose Escalation Phase, VIC-1911 doses were administered PO 
b.i.d. Days 1 – 4, 8 – 11 and 15 – 18 of a 28-day cycle in DL1, 2, 2.1, 2.2 and 3. In an expanded 
DL 2.1 (200 mg b.i.d.), doses were administered PO b.i.d. Days 1 – 4, 8 – 11, 15 – 18 and 22 – 25 
of a 28-day cycle (DL 2.1 continuous). 
A total of 74 patients were enrolled and treated in the study, 34 patients in the Dose Escalation 
portion and 40 patients in the Expansion portion. In the Dose Escalation Phase, the MTD was 
determined to be DL 2.2 (250 mg b.i.d.) and the RP2D was established at 200 mg b.i.d. 
administered on Days 1-4, 8-11 and 15-18 of a 28-day cycle. The Expansion portion included 10 
patients with SCLC, 9 patients with breast cancer, 13 patients with a MYC-amp/B-cat mutation, 
and 8 patients with other tumor types. All Expansion Phase patients received VIC-1911 at the 
RP2D of 200 mg PO b.i.d. Days 1 – 4, 8 – 11 and 15 – 18 of a 28-day cycle.  
In the Dose Escalation Phase, no patient had a confirmed complete response (CR) or a confirmed 
partial response (PR). A total of 14 (41.2%) patients had SD: 6 patients in DL 2 (150 mg b.i.d.), 4 
patients in DL 2.1 (200 mg b.i.d.), and 4 patients in DL 2.1 continuous (200 mg b.i.d. continuous). 
One patient in DL 2 (150 mg b.i.d.) had an unconfirmed PR.  
In the Expansion Phase, no patients had a confirmed CR or PR. A total of 14 (35.0%) patients had 
SD: 5 patients with SCLC, 1 patient with breast cancer, 5 patients with MYC-amp/B- cat mutation, 
and 3 patients with other solid tumors (2 patients with mesothelioma and 1 patient with colon 
cancer. The target ORR of ≥ 20% for each specific indication (or ≥ 10% for patients who were 
MYC+) for any indication was not met. Therefore, the study was discontinued.  
VIC-1911 mean maximum observed plasma concentration (Cmax) and area under the plasma 
concentration-time curve (AUC) increased with increasing dose in a dose proportional manner.  
The rate of phospho-histone H3 (pHH3) positive cells to total cells in paired skin samples was 
assessed. The mean pHH3 positive rate increased after VIC-1911 administration, thus confirming 
the mechanism of action of AurA kinase inhibition, with cell cycle arrest in mitotic assembly. 
In the Dose Escalation Phase, the most frequently reported treatment emergent adverse events 
(TEAEs) were fatigue (52.9%), diarrhea (41.2%), cough (29.4%), dyspnea (26.5%), and decreased 
appetite (26.5%). The most frequently reported TEAEs considered to be treatment-related were 
fatigue (32.4%), diarrhea (23.5%), nausea (14.7%), corneal epithelial microcysts (14.7%), 
vomiting (11.8%), vision blurred (11.8%), and decreased appetite (11.8%).  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
38 
November 11, 2022 
 
Amendment 2 
 
 
In the Expansion Phase, the most frequently reported TEAEs were diarrhea (45.0%), fatigue (35.0 
%), nausea (30.0%), ALT increased (25.0%), anemia (35.0%), and decreased appetite (32.5%). 
The most frequently reported TEAEs considered to be treatment-related were diarrhea (32.5%), 
decreased appetite (17.5%), ALT increased (15.0%), AST increased (15.0%), vision blurred 
(15.0%), anemia (15.0%), fatigue (15.0 %), nausea (12.5%), lipase increased (12.5%), and 
vomiting (12.5%).  
In the Dose Escalation Phase, the most frequently reported Grade 3 or higher TEAEs were diarrhea 
(14.7%) and lipase increased (11.8%). The most frequently reported Grade 3 or higher TEAEs 
considered to be treatment-related were diarrhea and lipase increased, each reported for 3 patients 
(8.8%).  
In the Expansion Phase, the most frequently reported Grade 3 or higher AEs were lipase increased 
(12.5%), and anemia (10.0%). The most frequently reported Grade 3 or higher TEAEs considered 
to be treatment-related was lipase increased, which occurred in 3 patients (7.5%). 
Despite > 97% of patients experiencing AEs in both the Dose Escalation and Expansion Phases of 
the study, VIC-1911 was well tolerated, as evidenced by the low frequency of treatment 
discontinuations due to AEs. Serious adverse events (SAEs) were reported for approximately 40% 
of patients in each Phase. One death on Day 30 was reported in the Dose Escalation Phase, which 
was due to rapid disease progression. Few patients experienced Grade 3 and 4 laboratory test 
results or deterioration of ECOG performance status from baseline.  
Nine patients experienced 11 ocular-related AEs (conjunctival hemorrhage [200 mg b.i.d.], corneal 
epithelial microcysts [200, 250 and 300 mg b.i.d.], keratitis [200 mg b.i.d.], and blurred vision 
[150 – 250 mg b.i.d.]). Expert review of the events determined that, as with other oncolytic agents, 
VIC-1911 may cause dose-dependent, temporary, and reversible ocular effects. 
3.4.2. 
Clinical Studies of Other AurA Kinase Inhibitors 
In Phase 1 and 2 clinical trials in advanced solid tumors with alisertib (N = 273), the most 
frequently reported TEAEs in ≥ 10% of subjects were neutropenia, alopecia, diarrhea, leucopenia, 
nausea, stomatitis, fatigue, decreased appetite, somnolence, vomiting, oral candidiasis, 
thrombocytopenia, anemia, febrile neutropenia and confusional state (memory impairment). The 
most frequently reported Grade ≥ 3 TEAEs were neutropenia, leucopenia, febrile neutropenia, 
anemia, diarrhea, fatigue, nausea, stomatitis and vomiting.28,29 
3.4.3. 
Sotorasib (LUMAKRAS™) 
3.4.3.1. 
Warnings and Precautions23 
• Hepatotoxicity: Monitor liver function tests every 3 weeks for the first 3 months of 
treatment than once monthly as clinically indicated. Withhold, reduce dose, or permanently 
discontinue LUMAKRAS based on the severity. 
• Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary 
symptoms. Immediately withhold LUMAKRAS for suspected ILD/pneumonitis and 
permanently discontinue if no other potential causes of ILD/pneumonitis are identified. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
39 
November 11, 2022 
 
Amendment 2 
 
 
3.4.3.2. 
Adverse Reactions 
The most common adverse reactions (≥ 20%) for LUMAKRAS are diarrhea, musculoskeletal pain, 
nausea, fatigue, hepatoxicity, and cough. The most common laboratory abnormalities ≥ 25% are 
decreased lymphocytes, decreased hemoglobin, increased AST, increased ALT, decreased 
calcium, increased alkaline phosphatase, increased urine protein and decreased sodium.23 
3.4.4. 
Potential Overlapping Toxicities of VIC-1911 in Combination with Sotorasib 
Based on the clinical toxicities of AurA kinase inhibitors, VIC-1911 and alisertib, and KRAS 
G12C inhibitor, sotorasib, potential overlapping toxicities of VIC-1911 in combination with 
sotorasib may include diarrhea, nausea, vomiting, decreased appetite, anemia, and increased liver 
enzymes (ALT and AST).  
3.5. 
Dose Rationale 
3.5.1. 
VIC-1911 
In the VIC-1911 Phase 1 study in advanced solid tumors, the MTD was 250 mg b.i.d. and the 
RP2D was 200 mg b.i.d., Days 1-4, 8-11 and 15-18 (e.g., 4 days on, 3 days off) for 3 weeks of a 
28-day cycle.  
For the combination VIC-1911 plus sotorasib dose groups in Phase 1a (Dose Escalation) and Phase 
1b (Expansion) of the study, VIC-1911 will be administered on the 4 days on, 3 days off schedule 
as described in Section 5.1 below.  
For the VIC-1911 monotherapy dose groups in the Dose Escalation and Expansion Phases of the 
study, VIC-1911 will be administered on a continuous dosing schedule. The rationale for 
continuous dosing is supported by preclinical studies in which continuous dosing was found to be 
more effective than intermittent dosing, and to maximize the potential for clinical benefit while 
reducing the potential for Cmax-related toxicities that were observed on the 4 days on 3 days off 
dosing schedule in the previous Phase 1 study (TO-TAS-119-102). To support the continuous 
dosing schedule, pharmacokinetic modeling was performed to predict exposure over a 1-month 
period under a continuous dosing regimen vs. the RP2D of 200 mg b.i.d. 4 days on 3 days off for 
3 weeks, repeated every 28 days. The exposure (AUC0-672) at 200 mg b.i.d. 4/3 for 3 weeks vs. 75 
mg and 100 mg b.i.d. continuous daily dosing was 437,000 vs. 374,000 and 498,000 h*ng/mL 
respectively. For the current study, we have set the threshold for observed cumulative exposure 
not to exceed the RP2D of 200 mg b.i.d. 4 days on, 3 days off for 3 weeks, repeated every 28 days 
cumulative exposure (AUC) of 437,000 h*ng/mL. Thus, the VIC-1911 doses in this study will 
start at 25 mg b.i.d. and escalate to 50, 75 and 90 mg b.i.d. in the Dose Escalation Phase, and the 
RP2D determined on the continuous schedule will be utilized in the Expansion Phase. See Section 
5.1.   
3.5.2. 
Sotorasib 
Sotorasib will be evaluated at the approved dose and schedule for treatment KRAS G12C-mutated 
locally advanced or metastatic NSCLC, 960 mg q.d., with dose reductions for toxicity.23 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
40 
November 11, 2022 
 
Amendment 2 
 
 
Therefore, in the combination Dose Escalation Phase of this study, VIC-1911 will be administered 
twice daily starting at Dose Level -1 from the MTD established in an earlier monotherapy Phase 
1 study (TO-TAS-119-102) on Days 1-4, 8-11 and 15-18 for 3 weeks repeated every 28 days in 
combination with sotorasib at a dose of 960 mg orally once daily continuously, with VIC-1911 
and sotorasib dose reduction criteria for management of toxicity. In the combination Expansion 
Phase, VIC-1911 plus sotorasib will be administered at the MTDs established for both drugs in the 
combination Dose Escalation Phase of the study.  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
41 
November 11, 2022 
 
Amendment 2 
 
 
4. 
TRIAL OBJECTIVES AND PURPOSE 
4.1. 
Primary Objectives  
• Phase 1a (Dose Escalation Phase): To determine the safety, tolerability, 
maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D) of: 
• VIC-1911 monotherapy in subjects previously treated with KRAS G12C 
inhibitor therapy, 
• VIC-1911 in combination with sotorasib (LUMAKRAS™) in subjects 
previously treated with KRAS G12C inhibitor therapy, and  
• VIC-1911 in combination with sotorasib in subjects naïve to KRAS G12C 
inhibitor therapy 
• Phase 1b (Expansion Phase): To determine the objective response rate (ORR), 
defined as complete response (CR) or partial response (PR), for: 
• VIC-1911 monotherapy in subjects previously treated with KRAS G12C 
inhibitor therapy,  
• VIC-1911 in combination with sotorasib in subjects previously treated with 
KRAS G12C inhibitor therapy, and  
• VIC-1911 in combination with sotorasib in subjects naïve to KRAS G12C 
inhibitor therapy 
4.2. 
Secondary Objectives  
The following parameters will be evaluated for VIC-1911 monotherapy and in combination with 
sotorasib:  
• Phase 1a (Dose Escalation Phase):  
• ORR 
• Duration of response (DoR) 
• Time to response (TTR) 
• Disease control rate (DCR), defined as SD, CR or PR  
• Progression-free survival (PFS) 
• Overall survival (OS) 
• Pharmacokinetics (PK) of VIC-1911 monotherapy and in combination with sotorasib 
• Pharmacodynamics of tumor biomarker determinations pre- and on-study summarized 
and correlated with clinical outcome 
• In subjects with refractory to or relapsed on prior KRAS G12C inhibitor therapy, the 
effect of prior KRAS G12C de novo resistance (KRAS G12C inhibitor treatment ≤ 3 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
42 
November 11, 2022 
 
Amendment 2 
 
 
months) versus KRAS G12C acquired resistance (KRAS G12C inhibitor treatment > 3 
months) on clinical outcome 
• Phase 1b (Expansion Phase):  
• Safety and tolerability of VIC-1911 monotherapy and in combination with sotorasib 
• Duration of response (DoR) 
• Time to response (TTR) 
• Disease control rate (DCR), defined as SD, CR or PR  
• Progression-free survival (PFS) 
• Overall survival (OS) 
• Pharmacodynamics of ctDNA and tumor biomarker determinations pre- and on-study 
summarized and correlated with clinical outcome 
• In subjects with refractory to or relapsed on prior KRAS G12C inhibitor therapy, the 
effect of prior KRAS G12C de novo resistance (KRAS G12C inhibitor treatment ≤ 3 
months) versus KRAS G12C acquired resistance (KRAS G12C inhibitor treatment > 3 
months) on clinical outcome 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
43 
November 11, 2022 
 
Amendment 2 
 
 
5. 
INVESTIGATIONAL PLAN 
5.1. 
Overall Study Design 
This is a non-randomized, open-label Phase 1a/1b study of aurora kinase A inhibitor VIC-1911 
administered as monotherapy and in combination with sotorasib for the treatment of locally 
advanced or metastatic KRAS G12C-mutant non-small cell lung cancer (NSCLC). 
Selected subjects will include males and females age ≥18 years with histologically confirmed 
locally advanced or metastatic KRAS G12C-mutated NSCLC, received at least 1 prior line of 
cancer therapy with a PD-1 or PD-L1 inhibitor with or without platinum-based chemotherapy 
(unless subject is not eligible or refuses chemotherapy or PD-1/PD-L1 therapy), previously treated 
with or naïve to G12C inhibitor therapy, recovered from all acute toxicities (< Grade 1) due to 
prior therapy, have adequate hematological, renal and hepatic function and no known history of 
significant cardiac, hepatic or ocular disease. 
Phase 1a (Dose Escalation Phase):  
Following screening, a total of up to 36 subjects are anticipated to establish the MTDs of VIC-
1911 monotherapy and VIC-1911 in combination with sotorasib therapy.  
Cohort 1a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will 
receive VIC-1911 monotherapy. Up to 24 subjects are anticipated in this cohort.  
VIC-1911 will be administered orally twice daily (b.i.d.) at doses of 25, 50, 75 and 90 mg (total 
daily doses of 50, 100, 150 and 180 mg) repeated every 28 days (=1 cycle) (Table 7). Subjects will 
take their VIC-1911 b.i.d. doses in the fasted state (1 hour before or 2 hours after the morning and 
evening meal), with the two doses approximately 12 hours apart. 
Table 7: VIC-1911 Monotherapy Dose Escalation Levels 
Dose Level 
VIC-1911 (PO b.i.d.) 
1 
25 mg 
2 
50 mg 
3 
75 mg 
4 
90 mg 
VIC-1911-related AEs will lead to individual dose reductions as indicated in Section 5.5.1.2.  
Cohort 1b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy or 
are naïve to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination 
therapy. Up to 12 subjects are anticipate in this cohort.  
VIC-1911 will be administered orally twice daily (b.i.d.) at the doses indicated below on Days 1-
4, 8-11, and 15-18 repeated every 28 days (=1 cycle) and sotorasib will be administered once daily 
at the doses indicated in Table 8. Both VIC-1911 and sotorasib will be taken together in the fasted 
state (1 hour before or 2 hours after the morning meal and after the evening meal [VIC-1911 only]), 
with the VIC-1911 b.i.d. doses approximately 12 hours apart.  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
44 
November 11, 2022 
 
Amendment 2 
 
 
Table 8: Combination VIC-1911 Plus Sotorasib Dose Escalation Levels 
Dose Level 
VIC-1911 (PO b.i.d.)a 
Sotorasib (PO q.d.) 
1 
75 mg  
960 mg 
2 
150 mg  
960 mg 
3 
200 mg 
960 mg 
a Days 1-4 x 3 weeks q 28 days 
VIC-1911 and sotorasib (LUMAKRAS)-related AEs will lead to individual dose reductions as 
indicated in Section 5.5.1.2.   
Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will be enrolled 
alternatingly into Cohort 1a (VIC-1911 monotherapy) and Cohort 1b (VIC-1911 plus sotorasib) 
by dose level (e.g., Dose Level 1 in Cohort 1a will be filled, then Dose Level 1 in Cohort 1b, then 
Dose Level 2 in Cohort 1a, etc.). In Cohort 1b, VIC-1911 pharmacokinetics will be analyzed from 
Dose Level 1 before Dose Level 2 is initiated to assess the impact of co-administration of VIC-
1911 plus sotorasib on the pharmacokinetics of VIC-1911. If necessary, a dose adjustment to VIC-
1911 will be made prior to initiating Dose Level 2. This information will be used to make a dose 
adjustment for Dose Level 3, if necessary.   
A 3+3 dose escalation schema will be followed for each cohort. A total of 3 subjects per cohort 
will be dosed and followed for 28 days through Cycle 1 for DLT. If 0 of 3 subjects experiences a 
DLT in Cycle 1, the next higher dose level cohort will open. However, if a DLT is experienced in 
1 of 3 subjects, the cohort will be expanded to 6 subjects. If 2 or more of 6 subjects per cohort 
experience DLT, further dose escalation will be subject to SRC review and recommendation. The 
highest dose level below the dose level eliciting DLT in ≥ 2 of 6 subjects will be declared the VIC-
1911 monotherapy MTD or the combination VIC-1911 plus sotorasib MTDs. A total of 6 subjects 
will be treated at the MTD(s) in each cohort.  
For dose de-escalation, if 1 of 3 subjects experiences a DLT at the de-escalated dose level, the 
cohort will be expanded to 6 subjects. If ≥ 2 of 6 subjects at that dose level experience a DLT, no 
further subjects will be treated at that dose level and the next lower dose level to enroll 0 of 3 or < 
2 of 6 subjects without DLT will be declared the MTD.  
Subjects in all cohorts who demonstrate clinical benefit (CR, PR or SD) will be allowed to continue 
therapy with VIC-1911 monotherapy or VIC-1911 plus sotorasib combination therapy until 
progression of disease (unless the subject is still benefiting clinically in the opinion of the treating 
physician, after discussion with the Medical Monitor, as described in Section 7.1.1.), observation 
of unacceptable AEs, intercurrent illness or changes in the subject’s condition that prevents further 
study participation.   
DLT is defined in Section 5.5.1.2.  
No intra-subject dose escalation will be allowed from previous dose levels until the subject has 
received ≥ 3 cycles of their assigned dose, all subjects at the higher dose level have completed 
Cycle 1 at that dose level (e.g., 3 – 6 subjects, as required to establish safety of the higher dose 
level) and no ≥ Grade 3 toxicity, irrespective of causality, was observed during the previous 
treatment cycle. Subjects who experience a DLT may continue treatment in subsequent cycles at 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
45 
November 11, 2022 
 
Amendment 2 
 
 
the next lower dose level(s) until disease progression (or until no longer benefiting clinically) or 
unacceptable toxicity.  
Subjects who experience DLT at the first dose level in each cohort will not be dose-reduced and 
will be discontinued.  
A total of at least 6 subjects will be treated at the MTD in each group before initiating the 
Expansion Phase.  
A Safety Review Committee (SRC), consisting of the actively recruiting investigators, Sponsor 
Medical Monitor, and study staff, will review safety and efficacy data from each cohort monthly 
more often as necessary. Intermediate dose levels may be added it is recommended to do so by the 
SRC.  
Phase 1b (Expansion Phase): Following screening, a total of 104 subjects with KRAS G12C-
mutated locally advanced or metastatic NSCLC are anticipated to expand the disease treatment 
settings of VIC-1911 as monotherapy or in combination with sotorasib. VIC-1911 monotherapy 
and VIC-1911 plus sotorasib combination therapy will be administered orally at the MTDs/RP2Ds 
established during the Dose Escalation Phase. 
VIC-1911 and sotorasib will be taken in the fasted state, 1 hour before or 2 hours after a meal. 
VIC-1911 dose reductions for suspected VIC-1911-related toxicity will be followed in accordance 
with those established in the Dose Escalation Phase. Sotorasib dose reductions for suspected 
sotorasib-related toxicity will be 480 mg q.d. (Dose Level -1) and 240 mg q.d. (Dose Level -2) in 
accordance with the LUMAKRAS U.S. Product Label. Further detail on dose reduction guidelines 
for VIC-1911 and sotorasib are found in Section 5.5.1.2.  
Subjects who demonstrate clinical benefit (CR, PR or SD) will be allowed to continue therapy 
with VIC-1911 and sotorasib until progression of disease (unless the subject is still benefiting 
clinically in the opinion of the treating physician, after discussion with the Medical Monitor, as 
described in Section 7.1.1.), observation of unacceptable AEs, intercurrent illness or changes in 
the subject’s condition that prevents further study participation.   
The statistical objective is the evaluation of ORR, defined as CR or PR. The sample sizes are based 
on Simon’s 2-stage optimal design.30  
Cohort 2a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will 
receive VIC-1911 monotherapy.  The null hypothesis that the true OR rate (p0) ≤ 5% will be tested 
against a one-sided alternative true OR rate (p1) ≥ 20%. In the first stage, 10 subjects will be 
accrued. If there are 0 ORs in these 10 subjects, the cohort will be terminated due to futility. If 
there is at least 1 OR in these 10 subjects, 19 additional subjects will be accrued for a total of n = 
29 evaluable subjects. The null hypothesis will be rejected if 4 or more responses are observed in 
a total of 29 evaluable subjects. The design yields a type 1 error rate of 0.05% and power of 80% 
when the true response rate is at least 20% and provides evidence of clinical utility to move forward 
with continued clinical development in this patient population.  
Cohort 2b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will 
receive VIC-1911 plus sotorasib combination therapy. The null hypothesis that the true OR rate 
(p0) ≤ 5% will be tested against a one-sided alternative true OR rate (p1) ≥ 20%. In the first stage, 
10 subjects will be accrued. If there are 0 ORs in these 10 subjects, the cohort will be terminated 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
46 
November 11, 2022 
 
Amendment 2 
 
 
due to futility. If there is at least 1 OR in these 10 subjects, 19 additional subjects will be accrued 
for a total of n = 29 evaluable subjects. The null hypothesis will be rejected if 4 or more responses 
are observed in a total of 29 evaluable subjects. The design yields a type 1 error rate of 0.05% and 
power of 80% when the true response rate is at least 20% and provides evidence of clinical utility 
to move forward with continued clinical development in this patient population.  
Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will be enrolled 
alternatingly into Cohort 2a (VIC-1911 monotherapy) and Cohort 2b (VIC-1911 plus sotorasib) 
(e.g., one subject in Cohort 2a, next subject in Cohort 2b, next subject in Cohort 2a, etc). 
Cohort 2c: Subjects who are naïve to KRAS G12C inhibitor therapy will receive VIC-1911 plus 
sotorasib combination therapy. The null hypothesis that the true OR rate (p0) ≤ 30% will be tested 
against a one-sided alternative true OR rate (p1) ≥ 50%. In the first stage, 15 subjects will be 
accrued. If there are 5 or fewer ORs in these 15 subjects, the cohort will be terminated due to 
futility. If there is at least 6 ORs in these 15 subjects, 31 additional subjects will be accrued for a 
total of n = 46 evaluable subjects. The null hypothesis will be rejected if 19 or more responses are 
observed in a total of 46 evaluable subjects. The design yields a type 1 error rate of 0.05% and 
power of 80% when the true response rate is at least 50% and provides evidence of clinical utility 
to move forward with continued clinical development in this patient population.  
A sample size of n = 46 evaluable subjects also yields a type 1 error rate of 0.05% and power of 
79% when the median PFS is 10 months (from 6 months historical) based on a one-sample log-
rank test.    
Monitoring guidelines for DLTs (= excess toxicity) are found in Section 11.2. 
An SRC, consisting of the actively recruiting investigators, Sponsor Medical Monitor, and study 
staff, will review safety and efficacy data from each cohort monthly or more often as necessary.  
The study design schema is depicted below.  
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
47 
November 11, 2022 
 
Amendment 2 
 
 
Study Assessments: 
Blood for hematology, coagulation parameters and serum chemistry determinations will be 
collected within 28 days prior to Cycle 1 Day 1; on Days 1 and 15 of Cycles 1-3; on Day 1 of each 
subsequent cycle and at the End of Treatment Visit.  
Urine will be collected for urinalysis within 28 days prior to Cycle 1 Day 1, on Day 1 of each 
subsequent cycle and at the End of Treatment visit. 
Electrocardiograms (ECGs) will be taken within 28 days prior to Cycle 1 Day 1, pre-dose and 
approximately 2 hours post-dose on Cycle 1 Day 1 and Day 15, and at the End of Treatment visit. 
Ophthalmic exams will be conducted within 28 days prior to Cycle 1 Day 1 and at the End of 
Treatment visit. Additional ophthalmologic examinations will be conducted during the study, if 
clinically indicated. Subjects should be educated on, and be instructed to, immediately report any 
signs of potential ocular toxicity so that the toxicity is identified and managed in a timely fashion. 
Blood for PK assessment of VIC-1911 plasma concentrations will be collected at Cycle 1 Day 1 
and Day 15 pre-dose, 15 and 30 minutes, 1, 2, 4, 8 and 24 hours following the first daily dose, and 
pre-first dose Cycles 2, 4 and 6. On Cycle 1 Day 1 and Day 15, the evening dose of VIC-1911 will 
be held and subjects will receive only a single morning dose of VIC-1911 to collect a full 
pharmacokinetic profile following a single dose of study drug at steady state (Phase 1a [Dose 
Escalation Phase] only). 
Blood for assessment of ctDNA will be collected for Expansion Phase Cohorts 2b and 2c pre-dose 
Cycle 1 Day 1 and at progression of disease for biomarker assessment.  
If clinically feasible, tumor biopsies will be collected on all subjects (Dose Escalation and 
Expansion phases) at Screening (archived or fresh) and on subjects in the Expansion Phase only 
at Cycle 3 Day 1 and at time of progression for biomarker assessment.  
Results of ctDNA and tumor biomarker assessment also will be correlated with clinical outcome 
(e.g., objective response, disease progression, resistance development). 
Disease assessments will be based on computed tomography (CT) or magnetic resonance imaging 
(MRI). Assessments will be obtained every 8 weeks until documented progressive disease (PD). 
5.2. 
Number of Subjects and Centers 
Phase 1a (Dose Escalation Phase): Up to 36 subjects are anticipated. Phase 1b (Expansion Phase): 
Up to 104 subjects are anticipated. The total number of subjects anticipated for the study is up to 
140 across 5 clinical sites. Additional clinical centers may be added to complete enrollment in a 
timely manner. 
5.3. 
Treatment Assignment 
This is a non-randomized, open-label Phase 1a/1b study.  
In Phase 1a (Dose Escalation Phase), subjects who are refractory to or relapsed on prior KRAS 
G12C inhibitor therapy will receive either VIC-1911 monotherapy or VIC-1911 plus sotorasib 
combination therapy. Subjects who are naïve to KRAS G12C inhibitor therapy will receive VIC-
1911 plus sotorasib combination therapy. The VIC-1911 monotherapy group will receive VIC-


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
48 
November 11, 2022 
 
Amendment 2 
 
 
1911 orally twice daily and the VIC-1911 plus sotorasib combination groups will receive VIC-
1911 orally twice daily and sotorasib orally once daily. Dose regimens for all cohorts are repeated 
every 28 days (= 1 cycle).  
Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will be enrolled 
alternatingly into Cohort 1a (VIC-1911 monotherapy) and Cohort 1b (VIC-1911 plus sotorasib) 
by dose level (e.g., Dose Level 1 in Cohort 1a will be filled, then Dose Level 1 in Cohort 1b, then 
Dose Level 2 in Cohort 1a, etc.). 
In Phase 1b (Expansion Phase), subjects who are refractory to or relapsed on prior KRAS G12C 
inhibitor therapy will receive VIC-1911 monotherapy (Cohort 2a) or VIC-1911 plus sotorasib 
combination therapy (Cohort 2b). Subjects who are naïve to KRAS G12C inhibitor therapy will 
receive VIC-1911 plus sotorasib (Cohort 2c). The VIC-1911 monotherapy group will receive VIC-
1911 orally twice daily and the VIC-1911 plus sotorasib combination group will receive VIC-1911 
orally twice daily and sotorasib orally once daily. Dose regimens for all cohorts are repeated every 
28 days (= 1 cycle).  
Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will be enrolled 
alternatingly into Cohort 2a (VIC-1911 monotherapy) and Cohort 2b (VIC-1911 plus sotorasib) 
(e.g., one subject in Cohort 2a, next subject in Cohort 2b, next subject in Cohort 2a, etc.). 
5.4. 
Duration of Study  
Accrual in the Dose Escalation Phase is expected to be 18 months. Accrual in the Expansion Phase 
is expected to be 18 months, with the last subject followed for up to 6 months. The total study 
duration is expected to be 42 months. The anticipated accrual rate in the Dose Escalation Phase is 
~ 2 – 3 subjects per month, and in the Expansion Phase is ~6 subjects per month. 
5.5. 
Dose Adjustment Criteria 
Subjects who experience a toxicity requiring dose reduction of either drug may continue at the 
next lower dose level until disease progression, unacceptable toxicity or changes in the subject’s 
condition that prevents further study participation. AEs considered for dose reduction should not 
include the events assessed by the investigator as exclusively related to the underlying disease, 
other medical condition or a concomitant medication/treatment.  
5.5.1. 
Safety Criteria for Adjustment or Stopping Doses 
5.5.1.1. 
Toxicity Grading Criteria 
Toxicity grading is based on NCI Common Terminology Criteria for Adverse Events (CTCAE) 
version 5.0 or higher; http://evs.nci.nih.gov/ftp1/CTCAE/About.html. 
5.5.1.2. 
Dose Modifications and Dose Reductions 
Dose-limiting toxicity (DLT) is defined as any one of the following events considered at least 
possibly related to VIC-1911 and/or sotorasib occurring within the first 28 days of study treatment 
(=DLT evaluation period): 
• Grade 4 hematologic toxicity for > 1 day 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
49 
November 11, 2022 
 
Amendment 2 
 
 
• Grade 3 febrile neutropenia (defined as absolute neutrophil count (ANC) < 1000/mm3 with 
a single temperature of ≥ 38.3C [≥ 101F] or sustained temperature of ≥ 38.0C [≥ 
100.4F] for more than 1 hour)  
• Grade 3 hematologic toxicity with complications (e.g., thrombocytopenia with bleeding) 
• Failure of Grade 3 thrombocytopenia, ANC or hemoglobin (Hb) to recover to Grade ≤ 1 
within 4 weeks despite the use of platelet and RBC transfusions and/or growth factors 
• ≥ Grade 3 non-hematologic toxicity not due to disease progression (excluding nausea, 
vomiting, constipation, pain, diarrhea or rash that is adequately controlled with supportive 
care and resolves to ≤ Grade 2 within 48 hours), or electrolyte disturbances unresponsive 
to correction within 24 hours 
• Laboratory abnormalities that satisfy the 3 components of Hy’s Law of drug-induced liver 
injury31: 1) ALT or AST elevation ≥ 3 times the upper limit of normal (ULN), 2) total 
bilirubin elevation > 2 times the ULN without initial findings of cholestasis (i.e., absence 
of alkaline phosphatase activity > 2 times the ULN), and 3) no other reason to explain the 
combination of increased ALT/AST and total bilirubin, such as viral hepatitis, preexisting 
or acute liver disease, or another drug capable of causing the observed injury  
• A treatment interruption for ≥ Grade 3 drug-related toxicity in Cycle 1 exceeding 7 days 
or inability to begin Cycle 2 for > 7 days due to drug-related toxicity  
• Other important medical event not clearly due to underlying disease or extraneous causes  
A DLT evaluable subject is one who receives study treatment and does not meet the criteria for 
subject replacement during the DLT evaluation period. 
The VIC-1911 monotherapy dose modification guidelines are outlined in Table 9. These guidelines 
are based on the toxicity profile of VIC-1911 established in preclinical toxicology studies, in which 
the most adverse findings were reversible following withdrawal of the drug, and on the emerging 
safety profile of VIC-1911 in previous Phase 1 studies as monotherapy and in combination with 
paclitaxel. Provisions are not made for dose levels below 25 mg b.i.d. If 25 mg b.i.d. is determined 
to be unsuitable based on toxicity as defined above, the subject will be permanently discontinued 
from VIC-1911 treatment.  
All AEs should be considered related to VIC-1911 and/or sotorasib except those with known 
causality outside of treatment with VIC-1911 or sotorasib, or those known to be associated with 
the subject’s disease state, other medical condition or a concomitant medication/procedure. Best 
attempts should be made by the treating physician to attribute each drug-related AE to VIC-1911, 
sotorasib or both (e.g., overlapping toxicity, such as diarrhea with both agents). If causality is 
assessed as related to both sotorasib and VIC-1911, the most conservative action for the toxicity 
based on both dose modification guidelines should be undertaken for both study drugs (e.g., for a 
specific toxicity, if either guideline states to interrupt study treatment, then both VIC-1911 and 
sotorasib should be interrupted).   
See Section 10.3.1 for the definition of an AE and Section 10.3.1.5.2 for assessment of study drug 
relationship to the AE. Use of supportive medications (e.g., anti-emetic, anti-diarrheal 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
50 
November 11, 2022 
 
Amendment 2 
 
 
medications) to manage AEs does not negate the need to first record the initial finding as an AE, 
with associated intensity and causality. 
Table 9: VIC-1911 Dose Modification Guidelines 
VIC-1911-Related 
Toxicity 
During a Cycle 
Dose Adjustment for Next 
Treatment Day 
Grade 1 
 
Continue treatment 
Maintain b.i.d. dose at 100% 
Grade 2 
First incidence 
Interrupt until resolved to Grade 0-1 Maintain b.i.d. dose at 100% 
Second incidence 
Interrupt until resolved to Grade 0-1 Reduce dose by 1 dose levela  
Third incidence despite 
dose reduction 
Interrupt until resolved to Grade 0-1 Reduce dose by 2 dose levelsa  
Fourth incidence despite 
dose reduction 
Discontinue treatment permanently 
Discontinue treatment 
Grade 3 
First incidence 
Interrupt until resolved to Grade 0-1 Reduce dose by 1 dose levela 
Second incidence 
Interrupt until resolved to Grade 0-1 Reduce dose by 2 dose levelsa 
Third incidence despite 
dose reduction 
Discontinue treatment permanently 
Discontinue treatment 
Grade 4 
First incidence 
Discontinue treatment permanently 
Discontinue treatment 
a Excluding Grade 2 or 3 nausea and vomiting controlled by antiemetics, insomnia, obesity/weight gain, 
infertility, amenorrhea, galactorrhea, glucose intolerance due to dexamethasone used as an antiemetic, 
asymptomatic hypercholesterolemia or hypertriglyceridemia, any Grade 2 non-clinically significant 
laboratory findings and any  Grade 3 nonhematological toxicities due to disease and disease 
progression.  
Sotorasib dose reduction guidelines are outlined in Table 10. 
Table 10: Sotorasib (LUMAKRAS) Dose Reduction Guidelines23 
Action 
Recommended Dose 
First Dose Reduction 
480 mg (4 tablets) once daily 
Second Dose Reduction 
240 mg (2 tablets) once daily 
Recommended sotorasib dose modification guidelines outlined in the U.S. Product Label are 
found in Table 11. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
51 
November 11, 2022 
 
Amendment 2 
 
 
Table 11: Sotorasib (LUMAKRAS) Dose Modification Guidelines23 
Adverse Reaction 
Severitya 
Dosage Modification 
Hepatotoxicityb  
Grade 2 AST or ALT with 
symptoms or Grade 3 to 4 AST or 
ALT 
• Withhold LUMAKRAS until 
recovery to ≤ Grade 1 or baseline 
• Resume LUMAKRAS at the 
next lower dose level 
AST or ALT > 3 times the ULN 
with total bilirubin > 2 times the 
ULN in the absence of alternative 
causes 
• Permanently discontinue 
LUMAKRAS 
Interstitial Lung Disease 
(ILD)/pneumonitisc  
Any Grade 
• Withhold LUMAKRAS if 
ILD/pneumonitis is suspected 
• Permanently discontinue 
LUMAKRAS if 
ILD/pneumonitis is confirmed 
Nausea or vomiting despite 
appropriate supportive care 
(including anti-emetic therapy)d  
Grade 3 to 4 
• Withhold LUMAKRAS until 
recovery to ≤ Grade 1 or baseline 
• Resume LUMAKRAS at the 
next lower dose level 
Diarrhea despite appropriate 
supportive care (including anti-
diarrheal therapy)d 
Grade 3 to 4 
• Withhold LUMAKRAS until 
recovery to ≤ Grade 1 or baseline 
• Resume LUMAKRAS at the 
next lower dose level 
Other adverse reactionsd 
Grade 3 to 4 
• Withhold LUMAKRAS until 
recovery to ≤ Grade 1 or baseline 
• Resume LUMAKRAS at the 
next lower dose level 
ALT = alanine aminotransferase, AST - aspartate aminotransferase, ULN = upper limit of normal 
a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or higher. 
b See Warnings and Precautions (5.1), LUMAKRAS U.S. Product Label   
c See Warnings and Precautions (5.2) LUMAKRAS U.S. Product Label 
d See Adverse Reactions (6.1) LUMAKRAS U.S. Product Label 
5.5.1.3. 
Schedule Adjustments for Toxicity 
• For each AE that occurs in a subject enrolled in VIC-1911 plus sotorasib combination 
cohorts, instructions for assessment and management of VIC-1911 and sotorasib doses 
should be followed, as provided in Table 9, Table 10 and Table 11. 
• The maximum delay allowed between treatment cycles for either VIC-1911 or sotorasib is 
2 weeks. If toxicity has not resolved after 2 weeks of delay, the Medical Monitor should 
be contacted to discuss permission for resuming treatment after a longer delay for subjects 
who are experiencing clinical benefit. 
• Subjects in the combination dose cohorts (Cohorts 1b, 2b or 2c) who require a dose delay 
or dose reduction for either VIC-1911 or sotorasib may continue the other drug 
uninterrupted. 
5.5.2. 
Supportive Care Guidelines 
• Medications may be administered for the management of symptoms associated with the 
administration of VIC-1911 or sotorasib, as required. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
52 
November 11, 2022 
 
Amendment 2 
 
 
• Prophylactic pre-medication will not be used routinely. Adequate treatment for nausea 
and/or vomiting and diarrhea is permitted during Cycle 1. After Cycle 1, prophylaxis of 
nausea and/or vomiting and diarrhea is permitted. 
• Granulocyte stimulating growth factors (e.g., G-CSF or GM-CSF) are allowed according 
to standard ASCO guidelines. 
• Erythropoiesis-stimulating agents, transfusions, etc. are permitted for management of 
hematologic toxicities. 
5.6. 
Criteria for Study Termination 
If the Sponsor, investigators, study monitor or regulatory officials discover conditions arising 
during the study that indicate that the study should be halted or that the study site should be 
terminated, this action may be taken after appropriate consultation between the Sponsor and 
investigators. 
Conditions that may warrant termination include, but are not limited to, the following: 
• The discovery of an unexpected, serious, or unacceptable risk to subjects enrolled in the 
study 
• A decision on the part of the Sponsor to suspend or discontinue testing, evaluation, or 
development of the product 
• Failure of an investigator to enroll subjects into the study at an acceptable rate 
• Failure of an investigator to comply with pertinent FDA regulations 
• Submission of knowingly false information from the study site to the Sponsor, study 
monitor or the FDA 
• Insufficient adherence to protocol requirements 
• Study termination and follow-up would be performed in compliance with the conditions 
set forth in 21 CFR 312.50 and 21 CFR 312.56. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
53 
November 11, 2022 
 
Amendment 2 
 
 
6. 
STUDY POPULATION 
6.1. 
Subject Inclusion Criteria 
Subjects must meet all the following criteria to participate in the study: 
Inclusion Criteria: 
1. Males and females  18 years of age 
2. Have locally advanced or metastatic histologically or cytologically confirmed NSCLC, 
KRAS G12C-mutated 
3. The presence of a KRAS G12C mutation should be established prior to entry as assessed in a 
CLIA qualified laboratory. Testing may be done on tumor tissue (archival or fresh) or on 
ctDNA from blood. 
4. Have received at least 1 prior line of cancer therapy with a PD-1 or PD-L1 inhibitor with or 
without platinum-based chemotherapy (unless subject is not eligible or refuses chemotherapy 
or PD-1/PD-L1 therapy) and have documented progression on all prior cancer therapies 
5. Phase 1a (Dose Escalation Phase): 
5.1 Cohort 1a: (VIC-1911 monotherapy): Locally advanced or metastatic NSCLC refractory 
to or relapsed on at least 1 prior cancer therapy as noted above, and relapsed/refractory 
on KRAS G12C inhibitor therapy as the most recent cancer therapy prior to study 
5.2 Cohort 1b: (VIC-1911 plus sotorasib): Locally advanced or metastatic NSCLC: 
5.2.1 Refractory to or relapsed on at least 1 prior cancer therapy as noted above, and 
relapsed/refractory on KRAS G12C inhibitor therapy as the most recent cancer 
therapy prior to study, or  
5.2.2 Refractory to or relapsed on at least 1 prior cancer therapy as noted above, and 
naïve to KRAS G12C inhibitor therapy  
6. Phase 1b (Expansion Phase):  
6.1 Cohort 2a: (VIC-1911 monotherapy): Locally advanced or metastatic NSCLC refractory 
to or relapsed on at least 1 prior cancer therapy as noted above, and relapsed/refractory 
on KRAS G12C inhibitor therapy as the most recent cancer therapy prior to study 
6.2 Cohort 2b: (VIC-1911 plus sotorasib): Locally advanced or metastatic NSCLC refractory 
to or relapsed on at least 1 prior cancer therapy as noted above, and relapsed/refractory 
on KRAS G12C inhibitor therapy as the most recent cancer therapy prior to study 
6.3 Cohort 2c: (VIC-1911 plus sotorasib): Locally advanced or metastatic NSCLC refractory 
to or relapsed on at least 1 prior cancer therapy as noted above, and naïve to KRAS G12C 
inhibitor therapy  
7. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 
8. Have discontinued previous treatments for cancer, except for sotorasib for subjects to receive 
VIC-1911 plus sotorasib combination treatment, and have resolution, except where 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
54 
November 11, 2022 
 
Amendment 2 
 
 
otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior 
cancer treatment, surgery, or radiotherapy to Grade ≤ 1  
9. Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2 
(Appendix A) 
10. Life expectancy of ≥ 3 months  
11. Subjects with brain metastases: 
11.1 KRAS G12C inhibitor naïve: Subjects with clinically stable (i.e., no increase in 
corticosteroid requirement) asymptomatic brain metastases are allowed without prior 
local therapy, as long as all lesions are each ≤ 1 cm. Prior local therapy is required (e.g., 
stereotactic radiosurgery [SRS], stereotactic body radiation therapy [SBRT], or surgery) 
for any lesion > 1 cm or any lesion that is symptomatic. 
11.2 KRAS G12C inhibitor pretreated: Subjects with clinically stable (i.e., no increase in 
corticosteroid requirement) asymptomatic brain metastases following prior local 
therapy (e.g., SRS, SBRT or surgery) are allowed    
12. Adequate hematologic without ongoing transfusion support: 
12.1 Hemoglobin (Hb) ≥ 8 g/dL 
12.2 Absolute neutrophil count (ANC) ≥ 1.0 x 109 cells/L 
12.3 Platelets ≥ 75 x 109 cells/L 
13. Adequate renal and hepatic function: 
13.1 Calculated creatinine clearance ≥ 50 mL/minute x 1.73 m2 per the Cockcroft-Gault 
formula (Appendix B) 
13.2 Total bilirubin ≤ 1.5 times the ULN, unless due to Gilbert’s disease, or < 3 times the 
ULN for subjects with liver metastases 
13.3 ALT/AST ≤ 2 times the ULN, or < 3 times the ULN for subjects with liver metastases 
14. Negative serum pregnancy test within 14 days prior to the first dose of study therapy for 
women of child-bearing potential (WCBP), defined as a sexually mature woman who has 
not undergone a hysterectomy or who has not been naturally post-menopausal for at least 
24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive 
months). Sexually active WCBP and male subjects must agree to use adequate methods to 
avoid pregnancy (oral, injectable, or implantable hormonal contraceptive; tubal ligation; 
intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) 
throughout the study and for 28 days after the completion of study treatment. 
15. Ability to provide written informed consent 
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
55 
November 11, 2022 
 
Amendment 2 
 
 
6.2. 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from the study: 
Exclusion Criteria: 
1. Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, 
myocardial infarction, unstable angina or heart disease defined by the New York Heart 
Association (NYHA) Class III or Class IV (Appendix C) 
2. QT interval corrected for rate (QTc) > 480 msec on the ECG obtained at Screening using 
Fridericia method for QTc calculation 
3. Medications that are inhibitors or inducers of UDP-glucuronosyltransferase (UGT) are 
prohibited in the Dose Escalation Phase 
4. History of corneal epithelial cysts or other ocular events leading to blurred vision, or has 
medically relevant abnormalities identified on screening ophthalmologic examination  
5. Symptomatic pneumonitis/interstitial lung disease requiring medical intervention 
6. Symptomatic central nervous system metastasis 
7. Leptomeningeal carcinomatosis 
8. Inability to swallow oral medication 
9. Gastrointestinal conditions that could impair absorption or tolerance of study drugs 
10. Current hematologic malignancies 
11. Second, active primary solid tumor malignancy that, in the judgement of the Investigator or 
Sponsor Medical Monitor, may affect the interpretation of results, with the exception of 
carcinoma in situ of any origin, non-muscle invasive bladder cancer, and Gleason < 3+3 
prostate cancer 
12. Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or 
hepatitis C virus (HCV) requiring treatment within the last week prior to study treatment 
13. Other active infection requiring IV antibiotic usage within the last week prior to study 
treatment 
14. Unable to tolerate marketed dose of KRAS G12C inhibitor on prior therapy for subjects to 
be enrolled in combination VIC-1911 plus sotorasib treatment cohorts. Alternatively, these 
subjects may be able to enroll in the VIC-1911 monotherapy treatment cohort, upon 
discussion with the Medical Monitor and Study Chair. 
15. Previous MEK or EGFR inhibitor therapy  
16. Any other medical intervention or other condition which, in the opinion of the Principal 
Investigator, could compromise adherence to study requirements or confound the 
interpretation of study results 
17. Receipt of an investigational product on a clinical trial within 5 elimination half-lives or 
within 28 days, whichever is shorter, prior to C1D1 on this study, or currently enrolled in a 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
56 
November 11, 2022 
 
Amendment 2 
 
 
clinical trial involving an investigational product or any other type of medical research 
judged not to be scientifically or medically compatible with this study 
18. Previously completed or withdrawn from any other study investigating an aurora kinase A 
inhibitor 
19. Known hypersensitivity to VIC-1911 or its components 
20. If female, pregnant, breast-feeding, or planning to become pregnant 
6.3. 
Discontinuation of Subjects 
Any subject may be removed from study treatment for the following reasons: 
• Subject withdrawal of the informed consent 
• Subject noncompliance 
• An increasing or unexpected pattern of unacceptable toxicity 
• Disease progression or confirmed loss of clinical response 
• Pregnancy 
• Investigator judgment when the well-being and best interest of the subject is compromised 
Subjects experiencing unacceptable toxicity should be removed from the study treatment and 
followed until complete resolution of toxicity, return to baseline or until stable and no further 
resolution is expected, and the End of Treatment visit (28 days after the last dose of study drugs) 
has been completed, whichever is later. Subjects will then enter the Long-term Follow-up Period.  
Individual subjects may be discontinued from the study by the investigator or Sponsor at any time 
if either person determines that it is not in the best interest of the subject to continue. 
Any subject who becomes pregnant during the study must be discontinued from the study 
treatment immediately but should be followed through delivery or termination of the pregnancy. 
Subjects should also notify the investigator if they become pregnant within 28 days following the 
last dose of study drug. The Sponsor also must be notified if a subject becomes pregnant on study. 
When a subject is discontinued from study treatment, they should complete the end-of-study 
assessments and report any SAEs for 28 days following the last dose of study drug. The date and 
the primary reason for discontinuation from treatment will be recorded on the electronic case report 
form (eCRF). 
6.3.1. 
Replacement of Study Subjects 
Subjects in the Dose Escalation and Expansion phases will be replaced in the following 
circumstance only: 
• Subjects who are screened but do not receive at least one dose of study drug (VIC-1911 or 
for the combination cohorts, VIC-1911 or sotorasib)  
Subjects in the Dose Escalation phase will be replaced in the following circumstances only: 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
57 
November 11, 2022 
 
Amendment 2 
 
 
• Subjects treated in Cycle 1 who do not complete 75% of their prescribed daily doses of 
VIC-1911 or sotorasib 
• Subjects who withdraw consent during Cycle 1 
• Subjects who do not complete Cycle 1 due to progression of disease or non-drug-related 
AEs 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
58 
November 11, 2022 
 
Amendment 2 
 
 
7. 
TREATMENT OF SUBJECTS 
7.1. 
Description of Treatment Plan  
7.1.1. 
Treatment Duration 
Treatment will continue until confirmation of disease progression, unacceptable toxicity, or subject 
decision to discontinue therapy.  
Subjects may continue treatment with study drugs beyond progressive disease if they are 
determined by the treating physician to be deriving clinical benefit from treatment and meet the 
following criteria: no decline in performance status, absence of rapid disease progression with 
threat to vital organs or critical anatomical sites, and no significant, unacceptable or irreversible 
toxicities related to study treatment. The decision to continue treatment beyond initial progression 
should be discussed with the Sponsor Medical Monitor. Additionally, in cases where the majority 
of the disease is stable or responding, progressing lesions may be treated with local therapy (e.g., 
resection or radiotherapy) and the subject may be continued on trial following local therapy. 
7.2. 
Concomitant Medications 
7.2.1. 
Permitted Medications 
All medications and other treatments taken by subjects 4 weeks before and throughout the study 
period will be recorded in the eCRF module. Any changes in documented, permitted concomitant 
medications being taken at the beginning of the clinical trial or added during the time the subject 
is participating in this study (through the End of Treatment Visit) must be recorded in the CRF 
module. 
7.2.2. 
Prohibited Medications and Medications to be Avoided 
• Concurrent anti-tumor therapy of any kind or any other investigational agent is prohibited.  
• VIC-1911 coadministration with inhibitors or inducers of UGTs is prohibited in the Dose 
Escalation Phase 
• Per LUMAKRAS U.S. Product Label23, the following medications should be avoided for 
coadministration:  
• Coadministration of sotorasib with proton pump inhibitors (PPIs) and histamine H2 
receptor antagonists. If an acid-reducing agent cannot be avoided, administer sotorasib 4 
hours before or 10 hours after a local antacid 
• Coadministration 
of 
sotorasib 
with 
strong 
CYP3A4 
inducers. 
See 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-
interactions-table-substrates-inhibitors-and-inducers#table3-3 
• Coadministration of sotorasib with strong CYP3A4 substrates for which minimal 
concentration changes may lead to therapeutic failures of the substrate. If 
coadministration cannot be avoided, adjust the substrate dosage in accordance with its 
Prescribing 
Information. 
See 
https://www.fda.gov/drugs/drug-interactions-


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
59 
November 11, 2022 
 
Amendment 2 
 
 
labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-
inducers#table3-2 
• Coadministration of sotorasib with P-gp substrates for which minimal concentration 
changes may lead to serious toxicities. If coadministration cannot be avoided, decrease 
the substrate dosage in accordance with its Prescribing Information. See 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-
interactions-table-substrates-inhibitors-and-inducers#table4-1 
7.3. 
Treatment Compliance 
VIC-1911 will be dispensed by the clinical site pharmacy for the subject to take on an outpatient 
basis between visits.   
Sotorasib (LUMAKRAS) will be supplied by prescription to the subject by the Investigator or 
trained designee for the subject to take on an outpatient basis between visits.    
All subjects will be supplied with Dosing Diaries to record their daily VIC-1911 and sotorasib 
treatment (as applicable), and any missed doses. The Diaries will be reviewed by the clinic staff at 
each study visit to assess treatment compliance.  
7.4. 
Randomization and Blinding 
Not applicable. Subjects who are refractory to or relapsed on prior KRAS G12C therapy will be 
enrolled alternatingly into Cohort 1a (VIC-1911 monotherapy) or Cohort 1b (VIC-1911 plus 
sotorasib) during the Dose Escalation Phase and into Cohort 2a (VIC-1911 monotherapy) or 
Cohort 2b (VIC-1911 plus sotorasib) during the Expansion Phase, as described above.   


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
60 
November 11, 2022 
 
Amendment 2 
 
 
8. 
STUDY DRUG MATERIALS AND MANAGEMENT 
8.1. 
VIC-1911 
8.1.1. 
Study Drug Description 
VIC-1911 is a selective and orally active small molecule inhibitor of AurA kinase. VIC-1911 drug 
product is supplied as an immediate release, film coated tablet in 2 strengths: 10 mg (round) and 
25 mg (caplet), white to off-white in color, for oral use. Inactive ingredients are lactose 
monohydrate, partly pre-gelantinized starch, hydroxypropyl cellulose, stearic acid, magnesium 
stearate, triacetin, hydroxypropyl methylcellulose, polyethylene glycol and titanium oxide. VIC-
1911 is manufactured by PCI, Pharma Services, Tredegar, Gwent, UK.  
8.1.2. 
Study Drug Packaging and Labeling 
The tablets are packaged in 50 mL High Density Polyethylene (HDPE) bottles. The bottles are 
sealed with a solid medicinal safe cap. Each bottle contains 60 tablets. The study drug bottles are 
labeled with the product name, dose strength and other information as per local regulatory 
requirements. 
8.1.3. 
Study Drug Storage 
VIC-1911 is demonstrated to be stable when stored in the defined container closure system. VIC-
1911 should be stored at room temperature (15 - 25C), protected from light.  
8.1.4. 
Administration 
VIC-1911 will be provided to the clinical site pharmacy directly from the drug distribution center 
designated by the Sponsor. Subjects should be scheduled to begin study therapy following 
completion of Enrollment process.  
VIC-1911 will be administered orally twice daily at the dose level prescribed per cohort 
(approximately every 12 hours).  
A sufficient supply of VIC-1911 will be dispensed to the subject by the investigator or trained 
designee for the subject to take on an outpatient basis between visits. 
The following instructions should be reviewed with the subject, and a written copy of the 
instructions should be provided to the subject: 
• Take the prescribed dose of VIC-1911 tablets (either 10 mg or 25 mg, or both) by mouth 
twice each day as prescribed. Take the second dose about 12 hours after the first dose.   
• Take the tablets with a full glass of water (approximately 8 ounces). Swallow the tablets 
whole.  
• Doses will be taken in the fasted state, approximately 1 hour before or 2 hours after a meal. 
Instructions will be given to take your morning dose 1 hour before or 2 hours after finishing 
breakfast and, approximately 12 hours later, your evening dose 1 hour before or 2 hours after 
finishing dinner.  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
61 
November 11, 2022 
 
Amendment 2 
 
 
• The dose may be reduced if side effects occur. If a dose reduction is required, the investigator 
or trained designee will provide instructions to you. Do not reduce the dose unless instructed 
by the investigator or trained designee.  
• If a scheduled dose of study drug is missed and less than 6 hours have passed since the 
scheduled dosing time, immediately take the missed dose. If more than 6 hours have passed 
since the scheduled dosing time, do not take the missed dose. Wait and take the next regularly 
scheduled dose.  
• If the dose is vomited after taking, do not retake the dose. Wait for the next scheduled dose. 
Record the vomiting episode on the Dosing Diary and how long after dosing the vomiting 
occurred. 
• Each day record the number and dosage of tablets taken on the Dosing Diary. If a dose is 
missed, include the reason the dose was not taken.  
• Return the Dosing Diary to the study doctor at each visit.  
• Return opened and unopened bottles in which the tablets were dispensed.  
• Adherence with the study treatment regimen must be assessed at each visit by checking the 
returned drug supply and reviewing the Dosing Diary. Study drug therapy must be reported 
accurately by the clinic staff on the appropriate eCRF.  
8.2. 
Sotorasib 
8.2.1. 
Description 
Sotorasib (LUMAKRAS) is an inhibitor of the RAS GTPase family and a specific inhibitor of 
KRAS G12C, a tumor-restricted, mutant-oncogenic form of the KRAS GTPase.  
Sotorasib is supplied as film-coated tablets for oral use containing 120 mg of sotorasib.  
See the sotorasib (LUMAKRAS) U.S. Product Label for additional information on study drug 
description.23  
8.2.2. 
Packaging and Labeling 
See the sotorasib (LUMAKRAS) U.S. Product Label.23 
8.2.3. 
Storage 
See the sotorasib (LUMAKRAS) U.S. Product Label.23 
8.2.4. 
Administration 
Subjects should be instructed to take sotorasib once daily at about the same time each day, at least 
1 hour before or at least 2 hours after finishing breakfast.  
Acid-reducing agents PPIs and histamine H2 receptor antagonists decrease the concentration of 
sotorasib. If an acid-reducing agent cannot be avoided, administer sotorasib 4 hours before or 10 
hours after a local antacid. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
62 
November 11, 2022 
 
Amendment 2 
 
 
Sotorasib coadministration with strong CYP3A4 inducers may decrease the concentration of 
sotorasib and should be avoided.  
Sotorasib coadministration with strong CYP3A4 substrates for which minimal concentration 
changes may lead to therapeutic failures of the substrate should be avoided. If coadministration 
cannot be avoided, adjust the substrate dosage in accordance with its Prescribing Information. 
Sotorasib coadministration with P-gp substrates for which minimal concentration changes may 
lead to serious toxicities should be avoided. If coadministration cannot be avoided, decrease the 
substrate dosage in accordance with its Prescribing Information. 
See Section 7.2.2 on avoidance of coadministration of sotorasib with acid-reducing agents, strong 
CYP3A4 inducers, CYP3A4 substrates and P-gp substrates.  
The subject may be advised to read the FDA-approved Patient Information found in the 
LUMAKRAS U.S. Product Label. See LUMAKRAS prescribing information for additional 
information.23 
The following instructions should be reviewed with the subject, and a written copy of the 
instructions should be provided to the subject: 
• Take the prescribed dose of sotorasib tablets by mouth once each day as prescribed. 
• Take the tablets with a full glass of water (approximately 8 ounces). Swallow the tablets 
whole.  
• Doses will be taken in the fasted state, approximately 1 hour before or 2 hours after a meal. 
Instructions will be given to take your morning dose 1 hour before or 2 hours after finishing 
breakfast.  
• The dose may be reduced if side effects occur. If a dose reduction is required, the investigator 
or trained designee will provide instructions to you. Do not reduce the dose unless instructed 
by the investigator or trained designee.  
• If a scheduled dose of study drug is missed and less than 6 hours have passed since the 
scheduled dosing time, immediately take the missed dose. If more than 6 hours have passed 
since the scheduled dosing time, do not take the missed dose. Wait and take the next regularly 
scheduled dose.  
• If the dose is vomited after taking, do not retake the dose. Wait for the next scheduled dose. 
Record the vomiting episode on the Dosing Diary and how long after dosing the vomiting 
occurred. 
• Each day record the number and dosage of tablets taken on the Dosing Diary. If a dose is 
missed, include the reason the dose was not taken.  
• Return the Dosing Diary to the study doctor at each visit.  
• Return opened and unopened bottles in which the tablets were dispensed.  
• Adherence with the study treatment regimen must be assessed at each visit by checking the 
returned drug supply and reviewing the Dosing Diary. Study drug therapy must be reported 
accurately by the clinic staff on the appropriate eCRF.  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
63 
November 11, 2022 
 
Amendment 2 
 
 
 
8.3. 
Study Drug Accountability 
The investigator must maintain accurate records of receipt of VIC-1911 study drug, dispensing 
information, and the prompt return or destruction of unused supplies. Drug accountability logs will 
be supplied to each clinical site for purposes of recording VIC-1911 study drug dispensation and 
will be monitored by Sponsor personnel. If the site has an electronic study drug accountability 
form that is in keeping with institutional practice and the form collects the same information as the 
forms supplied by the Sponsor, this form may be substituted for the Sponsor’s drug accountability 
forms. 
Sotorasib will be dispensed via on-label prescription. Study staff must verify that subjects were 
prescribed and received sotorasib at the correct dose on Day 1 of each cycle, assess compliance at 
each visit and perform a tablet count at the end of each cycle. 
8.4. 
Study Drug Handling and Disposal 
Unused or expired VIC-1911 will be destroyed per institutional policy. Unused sotorasib will be 
handled according to institutional policy. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
64 
November 11, 2022 
 
Amendment 2 
 
 
9. 
STUDY PROCEDURES 
See Schedule of Study Procedures in Appendix D.  
9.1. 
Screening Procedures 
The following evaluations are to be performed within 28 days of study treatment to determine 
subject eligibility: 
• Administration of informed consent 
• Medical history, physical examination and vital signs 
• ECOG Performance Status 
• Height and weight 
• The following laboratory tests: 
− Hematology 
− Coagulation 
− Serum Chemistry 
− Urinalysis  
• Beta HCG pregnancy test for WCBP 
• 12-lead ECG 
• Ophthalmologic examination 
• Review of concomitant medications 
• Baseline computed tomography (CT) or magnetic resonance imaging (MRI) of 
systemic and intracranial disease 
• Archived tumor tissue for pharmacodynamic assessment, or fresh biopsy, if clinically 
feasible  
9.2. 
Requirements During Treatment Cycle 1  
9.2.1. 
Cycle 1, Day 1 
• Abbreviated physical examination (may be performed within the previous 24 hours) 
• Vital signs (may be performed within the previous 24 hours) 
• ECOG Performance Status (may be performed within the previous 24 hours) 
• Weight (may be performed within the previous 24 hours) 
• The following lab tests 
− Hematology (if not performed within the previous 72 hours) 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
65 
November 11, 2022 
 
Amendment 2 
 
 
− Coagulation (if not performed within the previous 72 hours) 
− Serum chemistry (if not performed within the previous 72 hours) 
− Urinalysis (if not performed within the previous 72 hours) 
• 12-lead ECG, pre-dose and at approximately 2 hours post-dose (following first daily 
dose only) (pre-dose ECG may be performed within the previous 24 hours) 
• Review of concomitant medications 
• Begin VIC-1911 or VIC-1911 plus sotorasib treatment   
• Provide subject with VIC-1911 and sotorasib (if applicable) Dosing Diary to record 
study treatments 
• Peripheral blood collection in EDTA for PK assessments pre-dose, 15 and 30 minutes 
(± 5 minutes), 1 hour (± 15 minutes), 2 and 4 hours (± 30 minutes), 8 hours (± 1 hour) 
and 24 hours (± 2 hours) following the first daily dose. Withhold the evening dose of 
VIC-1911. On Cycle 1 Day 2, the morning doses of sotorasib and/or VIC-1911 will be 
delayed until completion of the Cycle 1 Day 1 24-hour post-first-dose blood draw. 
(Dose Escalation Phase only) 
• Peripheral blood collection in EDTA for pharmacodynamic assessments pre-dose 
(Expansion Phase Cohorts 2b and 2c only) 
• Assessment of AEs 
• Assessment for survival 
9.2.2. 
Cycle 1, Day 15 (± 1 day) 
• Vital signs 
• ECOG Performance Status 
• The following lab tests 
− Hematology 
− Coagulation 
− Serum chemistry 
• 12-lead ECG, pre-dose and at approximately 2 hours post-dose (following first daily 
dose only) 
• Review of concomitant medications 
• Assessment of AEs 
• Continue VIC-1911 or VIC-1911 plus sotorasib treatment. Withhold the evening dose 
of VIC-1911. On Cycle 1 Day 16, the morning doses of sotorasib and/or VIC-1911 will 
be delayed until completion of the Cycle 1 Day 15 24-hour post-first-dose blood draw 
(Dose Escalation Phase only). 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
66 
November 11, 2022 
 
Amendment 2 
 
 
• Review VIC-1911 and sotorasib (if applicable) Dosing Diary with subject 
• Peripheral blood collection in EDTA for PK assessments, pre-dose, 15 and 30 minutes 
(± 5 minutes), 1 hour (± 15 minutes), 2 and 4 hours (± 30 minutes), 8 hours (± 1 hour) 
and 24 hours (± 2 hours) following the first daily dose (Dose Escalation Phase only) 
• Assessment for survival 
9.3. 
Cycles 2 and 3 (to be performed within 3 days prior to Day 1 of each 
cycle, unless otherwise specified)  
• Abbreviated physical examination 
• Vital signs 
• ECOG Performance Status 
• Weight 
• The following lab tests 
− Hematology (also on Day 15)  
− Coagulation (also on Day 15) 
− Serum chemistry (also on Day 15) 
− Urinalysis 
• Review of concomitant medications 
• Assessment of AEs 
• Continue VIC-1911 or VIC-1911 plus sotorasib treatment  
• Review VIC-1911 and sotorasib (if applicable) Dosing Diaries with subject 
• Peripheral blood collection in EDTA for PK assessments pre-dose (Day 1, Cycle 2, 
Dose Escalation Phase only) 
• Tumor sample for pharmacodynamic assessment pre-dose, if clinically feasible (Day 
1, Cycle 3, Expansion Phase only) 
• Assessment for survival 
• CT or MRI for disease re-staging (every 8 weeks, ± 7 days) 
9.4. 
Cycle 4 and Beyond (To be performed within 3 days prior to Day 1 of 
each cycle, unless otherwise stated) 
• Abbreviated physical examination 
• Vital signs 
• ECOG Performance Status 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
67 
November 11, 2022 
 
Amendment 2 
 
 
• Weight 
• The following lab tests 
− Hematology 
− Coagulation 
− Serum chemistry 
− Urinalysis 
• Review of concomitant medications 
• Assessment of AEs 
• Continue VIC-1911 or VIC-1911 plus sotorasib treatment  
• Review VIC-1911 and sotorasib (if applicable) Dosing Diary with subject 
• Peripheral blood collection in EDTA for PK assessments pre-dose (Day 1, Cycles 4 
and 6 only) (Dose Escalation Phase only) 
• Assessment for survival 
• CT or MRI for disease re-staging (every 8 weeks, ± 7 days) 
9.5. 
At Relapse or Progression of Disease 
• Disease assessment for response 
• Review of concomitant medications 
• Assessment of AEs 
• Peripheral blood collection in EDTA for pharmacodynamic assessment (Expansion 
Phase Cohorts 2b and 2c only) 
• Tumor biopsy for pharmacodynamic assessment, if clinically feasible (Expansion 
Phase only) 
• Assessment for survival 
9.6. 
End of Treatment (28 Days After Last Dose of VIC-1911 or VIC-
1911 Plus Sotorasib Study Medication ± 5 days) 
• Physical examination 
• Vital signs 
• ECOG Performance Status 
• Weight 
• The following lab tests 
− Hematology 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
68 
November 11, 2022 
 
Amendment 2 
 
 
− Coagulation 
− Serum chemistry 
− Urinalysis 
• 12-lead ECG 
• Ophthalmologic examination 
• Review of concomitant medications 
• Assessment of AEs  
• Review VIC-1911 and sotorasib (if applicable) Dosing Diary with subject 
• Assessment for survival 
9.7. 
Long-Term Follow-Up 
Long-term follow-up will consist of a clinic visit or telephone call to assess survival every 3 
months for up to 6 months. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
69 
November 11, 2022 
 
Amendment 2 
 
 
10. 
DESCRIPTION OF ASSESSMENTS 
10.1. 
Safety Assessments 
Safety will be assessed through the monitoring of AEs, clinical laboratory parameters 
(hematology, coagulation parameters, serum chemistry, urinalysis), vital sign measurements, 
ECGs, ophthalmologic examinations and physical examinations. AEs will be classified according 
to the Medical Dictionary for Regulatory Affairs (MedDRA) and graded according to the NCI 
CTCAE version 5.0 or higher. 
10.2. 
Safety Parameters 
10.2.1. 
Vital Signs 
Vital sign measurements include temperature, blood pressure and pulse rate. Additional 
measurements may be obtained if clinically indicated. Any value considered clinically significant 
by the investigator will be recorded as an AE on the eCRF. Clinically significant changes compared 
to baseline values should be followed until clinical resolution. 
10.2.2. 
Weight and Height 
Weight will be measured at Screening, Day 1 of each treatment cycle, and the End of Treatment 
Visit. Height will be measured at screening. 
10.2.3. 
Physical Examination 
Complete physical examinations include the following body system evaluations: General 
Appearance, Skin, Musculoskeletal, Eyes, Ears, Nose, Throat, Cardiovascular, Chest, Abdomen, 
Lymph Nodes, and Neurological.  Symptom-oriented (abbreviated) evaluations will be performed 
at study visits where indicated, and otherwise when clinically indicated. 
10.2.4. 
Electrocardiogram (ECG) 
ECGs will be performed within 28 days prior to Cycle 1 Day 1, C1D1 and C1D15 and at the End 
of Treatment visit.  
10.2.5. 
Ophthalmologic Tests 
A complete eye examination, to include evaluation of the cornea, anterior chamber, lens, posterior 
chamber and retina, will be conducted on each eye independently within 28 days prior to Cycle 1 
Day 1, and at the End of Treatment visit. At each of these visits, a full ophthalmologic examination 
will be conducted, to include slit lamp examination, visual acuity testing, visual field testing, color 
vision test, tonometry (intraocular pressure [IOP]), optical coherence tomography (OCT), dilated 
indirect fundoscopy and color fundus photography with attention to retinal abnormalities. 
Additional ophthalmic evaluations, to include the full ophthalmologic examination described 
above, may be conducted during the study, if clinically indicated.  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
70 
November 11, 2022 
 
Amendment 2 
 
 
10.2.6. 
Laboratory Assessments 
Clinical laboratory tests include hematology, coagulation parameters, serum chemistry and 
urinalysis (Table 12). 
Table 12: Clinical Laboratory Parameters 
Hematology 
Coagulation 
Parameters 
Serum Chemistry 
Urinalysis 
Red blood cell count 
APTT 
Serum creatinine 
pH 
Hemoglobin 
PT (INR) 
BUN 
Blood 
Hematocrit 
 
Glucose (non-fasting) 
Nitrites 
White blood cell count 
 
Albumin 
Glucose 
Differential: 
 
AST 
Ketones 
   Neutrophils 
 
ALT 
Leucocytes 
   ANC 
 
LDH 
Protein 
   Lymphocytes 
 
Total bilirubin 
Microscopic exam 
   Monocytes 
 
Total protein 
 
   Eosinophils 
 
Alkaline phosphatase 
 
   Basophils 
 
Amylase 
 
Platelets 
 
Lipase 
 
 
 
Calcium 
 
 
 
Phosphorus 
 
 
 
Magnesium 
 
 
 
Sodium 
 
 
 
Potassium 
 
 
 
Chloride 
 
 
 
Bicarbonate 
 
10.3. 
Adverse Events and Serious Adverse Events 
10.3.1. 
Definition of Adverse Events 
10.3.1.1. Adverse Event 
An AE includes any noxious, pathological, or unintended change in anatomical, physiological, or 
metabolic functions as indicated by physical signs, symptoms, and/or laboratory changes occurring 
whether or not temporally associated with study drug administration and whether or not considered 
related to study drug. This definition includes an exacerbation of pre-existing medical conditions 
or events, intercurrent illnesses, hypersensitivity reactions, drug interactions, or clinically 
significant laboratory findings. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
71 
November 11, 2022 
 
Amendment 2 
 
 
An AE does not include the following: 
• Medical or surgical procedures, e.g., tooth extraction, transfusion, surgery (The medical 
condition that leads to the procedure is to be recorded as an AE.) 
• Pre-existing conditions or procedures present or detected at the start of the study that do 
not worsen 
• Hospitalization for elective surgeries or for other situations in which an untoward medical 
event has not occurred 
• Abnormal laboratory value, unless it is clinically significant 
• Overdose of study drug or concomitant medication unaccompanied by signs/symptoms (If 
sign/symptoms occur, the final diagnosis should be recorded as an AE.) 
• Pregnancy by itself, unless a complication occurs during pregnancy leading to 
hospitalization; in this case (The medical condition that leads to the hospitalization is to be 
recorded as the AE.) 
• A significant worsening of the disease under investigation which is captured as an efficacy 
parameter in this study and, thus, is not to be recorded as an AE. 
10.3.1.2. Serious Adverse Event 
An SAE is defined as an AE that results in any of the following outcomes: 
• Death 
• Life-threatening, i.e., immediate risk of death from the event as it occurred. (This does 
not include an AE that, had it occurred in a more serious form, might have caused death.) 
• Persistent or substantial disability/incapacitation 
• Results in or prolongs an existing inpatient hospitalization 
• Congenital anomaly/birth defect 
Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered serious when, based on medical judgment, they may jeopardize the subject or 
may require medical or surgical intervention to prevent one of the outcomes listed in this definition. 
10.3.1.3. Unexpected Adverse Event 
An AE or suspected adverse reaction is considered "unexpected" if it is not listed in the 
Investigator’s Brochure or is not listed at the specificity or severity that has been observed; or, is 
not consistent with the risk information described in the protocol or elsewhere. For example, under 
this definition, hepatic necrosis would be unexpected (by virtue of greater severity) if the 
Investigator’s Brochure referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral 
thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) if 
the Investigator’s Brochure listed only cerebral vascular accidents. 
"Unexpected," as used in this definition, also refers to AEs or suspected adverse reactions that are 
mentioned in the Investigator’s Brochure as occurring with a class of drugs or as anticipated from 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
72 
November 11, 2022 
 
Amendment 2 
 
 
the pharmacological properties of the investigational therapy but are not specifically mentioned as 
occurring with the investigational therapy. 
10.3.1.4. Adverse Event Reporting Period 
The AE reporting period begins from the date of the first dose of study drug(s) to 28 days following 
the last dose of study drug(s). 
10.3.1.5. Recording of Adverse Events 
Each AE should be recorded in standard medical terminology on the AE eCRF. Whenever 
possible, the AE should be evaluated and reported as a diagnosis rather than as individual signs or 
symptoms. For example, cough, runny nose, sneezing, sore throat, and head congestion should be 
reported as 'upper respiratory infection'. If a definitive diagnosis is not possible, the individual 
signs and symptoms should be recorded. Dates of start (onset) and stop (recovery), action taken, 
and outcome will be recorded on the AE eCRF. 
All clinically significant abnormal changes in laboratory parameters will be recorded as an AE on 
the AE module, with the following exceptions: clinically significant abnormal laboratory changes 
determined to be related to the study condition and concomitant conditions, e.g., diabetes, of which 
the investigator was previously aware and that have not worsened. 
The investigator will evaluate all AEs with regard to maximum intensity and relationship to study 
drug, as follows. 
10.3.1.5.1. Maximum Intensity 
Maximum intensity should be assigned using one of the severity grades as outlined in the NCI 
CTCAE, version 5.0 or higher; if the AE is not specifically listed in the CTCAE, use the following 
grades: 
• Grade 1: mild 
• Grade 2: moderate 
• Grade 3: severe 
• Grade 4: life-threatening or disabling 
• Grade 5: death 
10.3.1.5.2. Relationship to Study Drug 
The degree of certainty with which an AE is attributed to study drug (or alternative causes, e.g., 
natural history of the underlying diseases, concomitant therapy, etc.) will be determined by how 
well the event can be understood in terms of known pharmacology of the study drug and/or 
reactions of similar nature previously observed with study drug. Each AE will be assigned one of 
the following five categories: 
• Not related: There is not a temporal relationship to the study drug (e.g., too early, too 
late), or there is a reasonable causal relationship to another drug, concurrent illness, or 
circumstance. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
73 
November 11, 2022 
 
Amendment 2 
 
 
• Unlikely related: There is a temporal relationship to study drug, but there is not a reasonable 
causal relationship between the time of study drug administration and the AE (i.e., it is 
doubtful the AE is related to the study drug); could be reasonably explained by other 
factors, including underlying disease, complications, concomitant drugs, or concurrent 
treatment. 
• Possibly related: There is a reasonable temporal sequence from time of study drug 
administration (e.g., occurred in a time frame relevant to study drug dose); or for which the 
possibility of the study drug being the causative factor (e.g., existence of similar reports 
attributed to the study drug; reactions attributable to the pharmacological effect) could not 
be excluded, although other factors such as underlying disease, complications, concomitant 
drugs, or concurrent treatment are presumable. 
• Probably related: There is a reasonable temporal sequence from time of study drug 
administration; and for which the possibility of factors other than the study drug 
administration, such as underlying disease, complications, concomitant drugs, or 
concurrent treatment, could not be excluded as the cause. 
• Definitely related: Follows a clear temporal sequence from time of study drug 
administration; could not be possibly explained by the known characteristics of the 
subject's clinical state, environmental or toxic factors, or other modes of therapy 
administered to the subject; follows a response pattern known to be associated with study 
drug administration. 
10.3.1.6. Adverse Event Reporting 
Each AE is to be reported by the investigator as serious or non-serious according to the definitions 
above. This classification determines the regulatory reporting procedures to be followed as 
described in Table 13. 
Table 13: Reporting Guidelines for Adverse Events 
Gravity of AE 
Reporting Time to Sponsor 
Type of Report 
Serious 
Within 24 hours after the site 
becomes aware of the event 
Initial SAE Report/ 
Completed AE eCRF 
Non-Serious 
Per AE eCRF 
Completed AE eCRF 
Any SAE, regardless of relationship to investigational therapy that occurs within 28 days following 
the last dose of study drug must be reported to the Sponsor within 24 hours after the site becomes 
aware of the event. The investigator is encouraged to discuss with the Medical Monitor any adverse 
experiences for which the issue of reportability is unclear or questioned. If some information is 
not available at the time of awareness of the event, the initial report should be followed by 
submission of a more detailed SAE Report when follow-up information is available. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
74 
November 11, 2022 
 
Amendment 2 
 
 
If the SAE occurs more than 28 days after the last dose of study drug, SAEs should be reported 
only if considered related to VIC-1911 or sotorasib. In the event of subject death, the reason for 
death should be recorded as the SAE, with 'death' recorded as the outcome on the SAE Report. 
The SAE also will be recorded as an AE on the AE eCRF. Note: the SAE Report is different from 
the AE CRF. In areas of both forms where the same data are reported, the forms will be completed 
in a consistent manner. For example, the same term should be used for the AE on both forms, with 
the same start and stop dates, action taken, outcome, etc. A checkbox on the AE eCRF for whether 
the AE resulted in an SAE, will link the two types of reports for a given event. 
An SAE Report should be prepared with as much available information concerning the event as 
possible so that a written report can be filed with the appropriate regulatory authorities. If causality 
cannot be determined definitively at the time of the SAE occurrence, it is important to notify the 
Sponsor within the timeline stated above, and to attribute the relationship as 'Not Assessable' (only 
applicable for the initial SAE Report). When new significant information is obtained, and the 
outcome and attribution of the event is known, the investigator will communicate this in a follow-
up SAE Report. This relevant information will be provided in a timely manner to allow reporting 
to regulatory authorities within the required reporting period. Any SAE follow-up information 
requested by the Sponsor should be provided in a timely manner. 
As necessary, the SAE Report should be accompanied by relevant pages from the eCRFs, e.g., 
medical history, AEs, concomitant medications. Additional information may be requested by the 
Sponsor in an expedited manner to ensure that the initial reporting of the SAE made to the 
regulatory authorities complies with the required time frame. The Sponsor may be required to 
collect and report additional information to the regulatory authorities in a follow-up report, 
containing a final evaluation of the event, including copies of hospital reports, autopsy reports, or 
other relevant information. 
10.3.1.7. Adverse Event and Serious Adverse Event Follow-Up 
All AEs and SAEs should be followed until resolution, return to baseline, or until the point it is 
deemed that further recovery is unlikely. All measures required for AE management and the 
ultimate outcome of the AE will be recorded in the source document and AE eCRF. 
10.3.1.8. Ongoing Safety Evaluation 
A study safety evaluation will be conducted on a regular (monthly) basis by teleconference. Dose 
exposure, dose-limiting toxicity, AE/SAE profiles and clinical laboratory abnormalities, and other 
safety measures will be reviewed during each convened meeting. Subject accrual will not be 
interrupted during the regular scheduled safety evaluations. These discussions will be led by the 
Sponsor Medical Monitor and Principal Investigator. 
10.4. 
Efficacy Assessments  
Efficacy assessments will be determined on the basis of MRI and/or CT scans with best treatment 
response of CR, PR, SD or PD at any protocol-specified time point. TTR, DoR, DCR, PFS and OS 
will be evaluated. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
75 
November 11, 2022 
 
Amendment 2 
 
 
10.4.1. 
Efficacy Endpoints 
10.4.1.1. Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of subjects with objective response (OR) following 
VIC-1911 and VIC-1911 plus sotorasib treatment in the Expansion Phase of the study (Cohorts 
2a, 2b and 2c). OR includes a best response of CR or PR, as defined by RECIST v.1.133 
(Appendix E). 
10.4.1.2. Secondary Efficacy Endpoints 
Secondary efficacy endpoints include:  
• Duration of Response (DoR): length of time from the first evidence of objective response 
(CR, PR) to the first objective evidence of progression 
• Time to Response (TTR): length of time from date of first administration of study drug to 
first evidence of OR 
• Disease Control Rate (DCR): Proportion of subjects with best response of CR, PR or SD 
• Progression-Free Survival (PFS): length of time from the date of first administration of 
study drug to the first objective evidence of disease progression or death, whichever is 
earlier 
• Overall Survival (OS): length of time from the date of first administration of study drug to 
the date of death from any cause. 
• In subjects refractory to or relapsed on prior KRAS G12C inhibitor therapy, the effect of 
prior KRAS G12C de novo resistance versus KRAS G12C acquired resistance on clinical 
outcome  
10.4.2. 
Timing of Assessments to Determine Objective Response 
Disease assessments will be made every 8 weeks (± 7 days). Disease assessments may be made at 
other time points at the discretion of the Investigator. 
10.4.3. 
Timing of ctDNA and Tumor Pharmacodynamic Assessments  
Blood for assessment of ctDNA will be collected in the Expansion Phase Cohorts 2b and 2c pre-
dose Cycle 1 Day 1 and at progression of disease for biomarker assessment.  
If clinically feasible, tumor biopsies will be collected on all subjects (Dose Escalation and 
Expansion phases) at Screening (archived or fresh) and on subjects in the Expansion Phase only 
at Cycle 3 Day 1 and at time of progression for biomarker assessment.  
Results of ctDNA and tumor biomarker assessment also will be correlated with disease 
assessments made every 8 weeks. 
10.5. 
Pharmacokinetic Assessment 
Because plasma concentrations will be determined at a limited number of time points during the 
study, a complete pharmacokinetic profile of VIC-1911 at each dose level may not be possible. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
76 
November 11, 2022 
 
Amendment 2 
 
 
Limited pharmacokinetic analyses will be performed, as VIC-1911 monotherapy and when given 
in combination with sotorasib. Additionally, any identified DDIs between VIC-1911 and sotorasib 
will be characterized.  
10.6. 
Pharmacodynamic Assessment 
Assessment of ctDNA will be made in blood collected during the study, summarized and results 
correlated with clinical outcome (e.g., objective response, disease progression, resistance 
development).  
Tumor biomarkers will be analyzed for patterns of de novo and acquired resistance to AurA kinase 
and KRAS G12C inhibitor therapy on pre-study and on-study samples. See Appendix F for tumor 
correlative analysis plan. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
77 
November 11, 2022 
 
Amendment 2 
 
 
11. 
STATISTICAL METHODOLOGY 
11.1. 
Determination of Sample Size 
Phase 1a (Dose Escalation): A total of up to 36 subjects are planned in a 3+3 dose escalation 
schema (3 to 6 subjects in each of 6 dose levels). 
Cohort 1a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will 
receive VIC-1911 monotherapy. A total of up to 24 subjects are planned (3 to 6 subjects in each 
of 4 dose levels). A total of 6 subjects will be treated at the MTD before initiating Phase 1b 
(Expansion Phase), Cohort 2a.   
Cohort 1b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy or 
are naïve to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination 
therapy. A total of up to 12 subjects are anticipated to establish an MTD of VIC-1911 plus sotorasib 
(3 to 6 subjects in each of 2 dose levels). A total of 6 subjects will be treated at the MTD before 
initiating the Expansion Phase, Cohorts 2b and 2c. 
Phase 1b (Expansion Phase): The statistical objective is the evaluation of the ORR, defined as 
CR or PR. The sample sizes are based on Simon’s 2-stage optimal design.30  
Cohort 2a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will 
receive VIC-1911 monotherapy. The null hypothesis that the true OR rate (p0) ≤ 5% will be tested 
against a one-sided alternative true OR rate (p1) ≥ 20%. In the first stage, 10 subjects will be 
accrued. If there are 0 ORs in these 10 subjects, the cohort will be terminated due to futility. If 
there is at least 1 OR in these 10 subjects, 19 additional subjects will be accrued for a total of n = 
29 evaluable subjects. The null hypothesis will be rejected if 4 or more responses are observed in 
a total of 29 evaluable subjects. The design yields a type 1 error rate of 0.05% and power of 80% 
when the true response rate is at least 20% and provides evidence of clinical utility to move forward 
with continued clinical development in this patient population.  
Cohort 2b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will 
receive VIC-1911 plus sotorasib combination therapy. The null hypothesis that the true OR rate 
(p0) ≤ 5% will be tested against a one-sided alternative true OR rate (p1) ≥ 20%. In the first stage, 
10 subjects will be accrued. If there are 0 ORs in these 10 subjects, the cohort will be terminated 
due to futility. If there is at least 1 OR in these 10 subjects, 19 additional subjects will be accrued 
for a total of n = 29 evaluable subjects. The null hypothesis will be rejected if 4 or more responses 
are observed in a total of 29 evaluable subjects. The design yields a type 1 error rate of 0.05% and 
power of 80% when the true response rate is at least 20% and provides evidence of clinical utility 
to move forward with continued clinical development in this patient population.  
Cohort 2c: Subjects who are naïve to KRAS G12C inhibitor therapy will receive VIC-1911 plus 
sotorasib combination therapy. The null hypothesis that the true OR rate (p0) ≤ 30% will be tested 
against a one-sided alternative true OR rate (p1) ≥ 50%. In the first stage, 15 subjects will be 
accrued. If there are 5 or fewer ORs in these 15 subjects, the cohort will be terminated due to 
futility. If there is at least 6 ORs in these 15 subjects, 31 additional subjects will be accrued for a 
total of n = 46 evaluable subjects. The null hypothesis will be rejected if 19 or more responses are 
observed in a total of 46 evaluable subjects. The design yields a type 1 error rate of 0.05% and 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
78 
November 11, 2022 
 
Amendment 2 
 
 
power of 80% when the true response rate is at least 50% and provides evidence of clinical utility 
to move forward with continued clinical development in this patient population. 
A sample size of n = 46 evaluable subjects also yields a type 1 error rate of 0.05% and power of 
79% when the median PFS is 10 months (from 6 months historical) based on a one-sample log-
rank test.    
11.2. 
Monitoring Guidelines (Early Stopping Rules for Excess Toxicity) 
In the Dose Escalation Phase, DLT criteria dictate stopping rules. If 2 of 6 subjects experience 
DLT, no further dose escalation will be made, and the next lower dose will be declared the MTD. 
A minimum of 6 subjects will be enrolled in Phase 1a (Dose Escalation Phase) in each the VIC-
1911 monotherapy and VIC-1911 plus sotorasib combination cohorts, with no observed DLT 
during the DLT evaluation period, before opening the Expansion Phase. 
During the Expansion Phase, we will use continuous monitoring for excess toxicity using a 
Popcock-type boundary,32 with the following assumptions: DLT event probability = 0.30 (30%) 
with 0.05 (5%) desired probability of stopping early.  
The maximum planned sample sizes for the Expansion Phase Cohorts 2a and 2b are n = 29 each. 
In each of these cohorts, sequential boundaries will be used to monitor the rates of DLTs. The 
accrual will be halted if excessive numbers of DLTs are seen, that is, if the number of DLTs is 
equal to or exceeds bn out of n subjects with full follow-up through C1D28. This is a Pocock-type 
stopping boundary that yields the probability of crossing the boundary at most (probability of early 
stopping) when the rate of dose-limiting toxicity is equal to the acceptable rate (event probability 
θ). For the maximum planned samples sizes of n = 29 for each Cohorts 2a and 2b, the boundary is 
equivalent to testing the null hypothesis, after each subject, that the event rate is equal to 0.3, using 
a one-sided test level of 0.017846.  
The maximum planned sample size for the Expansion Phase Cohort 2c is n = 46. In this cohort, 
sequential boundaries will be used to monitor the rates of DLTs. The accrual will be halted if 
excessive DLTs are seen, that is, if the number of subjects with a DLT is equal to or exceeds bn 
out of n subjects with full follow-up through C1D28. This is a Pocock-type stopping boundary that 
yields the probability of crossing the boundary at most (probability of early stopping) when the 
rate of dose-limiting toxicity is equal to the acceptable rate (event probability θ). For the maximum 
planned samples size of n = 46 for Cohort 2c, the boundary is equivalent to testing the null 
hypothesis, after each subject, that the event rate is equal to 0.3, using a one-sided test level of 
0.011900. 
Each cohort in the Expansion Phase will be stopped if the number of subjects with a DLT is equal 
to or exceeds bn out of n subjects with completed follow up through C1D28. 
 
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
79 
November 11, 2022 
 
Amendment 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohorts 2a and 2b 
n 
bn 
1 
- 
2 
- 
3 
- 
4 
4 
5 
5 
6 
5 
7 
6 
8 
6 
9 
7 
10 
7 
11 
8 
12 
8 
13 
9 
14 
9 
15 
9 
16 
10 
17 
10 
18 
11 
19 
11 
20 
11 
21 
12 
22 
12 
23 
13 
24 
13 
25 
13 
26 
14 
27 
14 
28 
15 
29 
15 
Cohort 2c 
n 
bn 
1 
- 
2 
- 
3 
- 
4 
4 
5 
5 
6 
5 
7 
6 
8 
6 
9 
7 
10 
7 
11 
8 
12 
8 
13 
9 
14 
9 
15 
10 
16 
10 
17 
11 
18 
11 
19 
11 
20 
12 
21 
12 
22 
13 
23 
13 
24 
13 
25 
14 
26 
14 
27 
15 
28 
15 
29 
15 
30 
16 
31 
16 
32 
17 
33 
17 
34 
17 
35 
18 
36 
18 
37 
19 
38 
19 
39 
19 
40 
20 
41 
20 
42 
21 
43 
21 
44 
21 
45 
22 
46 
22 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
80 
November 11, 2022 
 
Amendment 2 
 
 
11.3. 
Analysis Populations 
The full analysis set (FAS) includes all subjects who are administered any fraction of a dose of 
VIC-1911 or VIC-1911 plus sotorasib study medication. For a particular measure, the per-protocol 
set (PPS) includes those subjects in the FAS who have a valid baseline and one or more post-
treatment assessments for that measure of interest. 
The PK population consists of all subjects in the FAS who complete a baseline and at least one 
follow-up PK assessment. 
The pharmacodynamic population consists of all subjects in the FAS who complete a baseline and 
at least one follow-up pharmacodynamic assessment. 
Efficacy analyses will be conducted separately by cohort for both Dose Escalation and Expansion 
phases of the study.    
11.4. 
Statistical Analysis Methods 
All data will be analyzed using SAS Version 9.4 or higher for Windows (SAS Institute, Cary, NC). 
Continuous variables will be summarized using number, mean, standard deviation, median, 
minimum, and maximum. Categorical variables will be summarized using number and 
frequencies. 
11.4.1. 
Safety Analysis 
11.4.1.1. Adverse Events 
All safety endpoints will be summarized using descriptive statistics and will be based on the FAS 
dataset. 
All AEs will be coded based on the Medical Dictionary for Regulatory Affairs (MedDRA; version 
24.0 or higher). An AE will be considered a TEAE if the onset is after the first dose of study drug 
or if the condition was present at baseline but worsened after the first dose. 
All AEs for each subject will be listed, including intensity grading, relationship to study drug, 
action taken and outcome. Subject listings of deaths, SAEs, and AEs leading to treatment 
discontinuation will be provided. Subject narratives will be provided for deaths, SAEs and other 
significant AEs. Summary tables will be prepared to examine TEAE severity and relationship to 
study treatment. 
AE summaries will be produced separately for each dose cohort and overall, each disease cohort 
by dose and overall, and by monotherapy and combination phases of the study. All summaries will 
show, by subject group, dose cohort and overall, the number and percentage of subjects 
experiencing at least 1 TEAE of each preferred term, arranged by system organ class, and the 
number of occurrences of the event. Separate summaries will be produced by relationship to study 
medication, by severity, and for those events with an incidence rate of at least 2% in any group or 
overall. 
SAEs will be summarized in a similar manner; overall, by relationship to study medication, and 
by severity. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
81 
November 11, 2022 
 
Amendment 2 
 
 
In addition to the above, summaries of the number and percentage of subjects discontinuing the 
study due to AEs and, due to death, will be presented. 
11.4.1.2. Laboratory Data 
Laboratory data will be listed by subject. Values above and below normal ranges will be indicated, 
and whether clinically significant. All laboratory values will be graded according to the NCI-
CTCAE criteria, version 5.0 or higher. Laboratory data will be summarized by actual value and 
change from baseline using number of non-missing observations, mean standard deviation, 
median, minimum and maximum. In addition, shift tables and the incidence of Grade 3 or 4 
laboratory values will be presented. 
11.4.1.3. Vital Signs 
Vital signs will be listed by subject. Values above and below normal ranges will be indicated as 
will clinical significance. Vital sign data will be summarized by actual value and change from 
baseline using number of non-missing observations, mean, standard deviation, median, minimum 
and maximum. 
11.4.1.4. Other Safety Data 
Data collected for physical examinations, ECGs, ophthalmologic examinations and related 
measures will be listed. 
11.4.2. 
Efficacy Analysis 
11.4.2.1. Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of subjects with objective response (OR) following 
VIC-1911 or VIC-1911 plus sotorasib treated at the MTDs/RP2Ds in the Expansion Phase of the 
study (Cohorts 2a, 2b and 2c).  OR will be summarized using number and percentage of subjects 
in each cohort with a best response of CR, PR, SD or PD assessed by RECIST v. 1.1,33 and 95% 
confidence intervals will be estimated. 
11.4.2.2. Secondary Efficacy Endpoints 
For the Dose Escalation Phase (Cohorts 1a and 1b), OR will be determined, as above, and 
summarized using number and percentage of subjects, with estimation of 95% confidence 
intervals.  
Other secondary endpoints will be summarized for all subjects in the Dose Escalation and 
Expansion phases of the study by cohort as follows: 
• The proportion of subjects with disease control (CR, PR or SD) will be summarized using 
the number and percentage of subjects with a best response rate of CR, PR, SD or PD 
assessed by RECIST v. 1.1.  
• DoR, TTR, PFS and overall survival will be summarized using the Kaplan-Meier product- 
limit method to estimate the median survival. Subjects who do not have disease 
progression will be censored at the last follow-up time. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
82 
November 11, 2022 
 
Amendment 2 
 
 
DoR will be calculated from the date of first evidence of response to the date of progression or 
death. 
TTR will be calculated from the date of first treatment to the date of first evidence of response. 
PFS will be calculated from the date of first treatment to the date of first evidence of progression 
or death. 
OS will be calculated from the date of first treatment to the date of death from any cause; subjects 
who do not experience death will be censored at the last follow-up time.  
In subjects refractory to or relapsed on prior KRAS G12C inhibitor therapy, the effect of prior 
KRAS G12C de novo resistance versus KRAS G12C acquired resistance on clinical outcome (e.g., 
OR, PFS, OS. 
11.4.3. 
Pharmacokinetic Endpoint Analysis 
Because plasma concentrations will be determined at a limited number of time points during the 
study, a complete pharmacokinetic profile of VIC-1911 at each dose level may not be possible. 
Limited pharmacokinetic analyses will be performed, as VIC-1911 monotherapy and when given 
in combination with sotorasib. Additionally, any identified DDIs between VIC-1911 and sotorasib 
will be characterized.  
11.4.4. 
Pharmacodynamic Endpoint Analysis 
Assessment of ctDNA will be made in blood collected during the study, summarized and results 
correlated with clinical outcome (e.g., objective response, disease progression, resistance 
development).  
Tumor biomarkers will be analyzed for patterns of de novo and acquired resistance to AurA kinase 
and KRAS G12C inhibitor therapy on pre-study and on-study samples. See Appendix F for tumor 
correlative analysis plan. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
83 
November 11, 2022 
 
Amendment 2 
 
 
12. 
STUDY MANAGEMENT 
12.1. 
Data Management 
The investigator is responsible for completing and maintaining adequate and accurate source 
documentation.  Source documentation constitutes original records, which may include progress 
notes, medication administration records, laboratory reports, ECG tracings, discharge summaries, 
eCRF worksheets, etc. Data for this study will be submitted electronically. Access to the database 
will be provided following a brief on-line training session. Each user will receive a unique 
username and password, which should not be shared. The investigator must sign the investigator’s 
statement for each subject indicating that the data reported are accurate. 
12.2. 
Monitoring 
The Sponsor is responsible for ensuring the proper conduct of the study with regard to ethics, 
protocol adherence, site procedures, integrity of the data, and applicable laws and/or regulations. 
At regular intervals during the study and following completion of the study, the Sponsor’s study 
monitors will contact the study site via visits to the site, telephone calls, and letters in order to 
review study progress, eCRF completion, and address any concerns or questions regarding the 
study conduct. During monitoring visits, the following aspects of study conduct will be carefully 
reviewed: informed consent of subjects, subject recruitment, subject compliance with the study 
procedures, source data verification, drug accountability, use of concomitant therapy by subjects, 
AE and SAE documentation and reporting, and quality of data.  Records pertaining to these aspects 
are expected to be kept current. 
12.3. 
Audits and Inspections 
Authorized representatives of the Sponsor, a regulatory authority, an Independent Ethics 
Committee (IEC) or an Institutional Review Board (IRB) may visit the site to perform audits or 
inspections, including source data verification. The purpose of a Sponsor audit or inspection is to 
systematically and independently examine all study-related activities and documents to determine 
whether these activities were conducted, and data were recorded, analyzed, and accurately reported 
according to the protocol, Good Clinical Practice (GCP) guidelines of the International Conference 
on Harmonization (ICH), and any applicable regulatory requirements. The investigator should 
contact the Sponsor, or Sponsor’s representatives, immediately if contacted by a regulatory agency 
about an inspection. 
12.4. 
Amendments 
Any amendments to the protocol will be written and approved by the Sponsor. All amendments 
must be submitted to the IRB for approval prior to implementing the changes. In some instances, 
an amendment requires changes to the informed consent document (ICD), which also must be 
submitted for IRB approval prior to administration to subjects. If any changes to the eCRFs are 
required, the Sponsor will issue supplemental or revised eCRFs on behalf of the Sponsor. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
84 
November 11, 2022 
 
Amendment 2 
 
 
12.5. 
Institutional Review Board 
The Principal Investigator must obtain IRB approval for the investigation.  Initial IRB approval, 
and all materials approved by the IRB for this study including the subject consent form and 
recruitment materials must be maintained by the Investigator and made available for inspection. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
85 
November 11, 2022 
 
Amendment 2 
 
 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor may 
conduct a quality assurance audit.  See Section 12.3 for more details regarding the audit process. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
86 
November 11, 2022 
 
Amendment 2 
 
 
14. 
ETHICS 
14.1. 
Ethics Review 
The final study protocol, including the final version of the ICD, must be approved or given a 
favorable opinion in writing by an IRB or Independent Ethics Committee (IEC) as appropriate.  
The investigator must submit written approval to the Sponsor, or the Sponsor’s representatives, 
before he or she can enroll any subject into the study. 
The Principal Investigator is responsible for informing the IRB or IEC of any amendment to the 
protocol in accordance with local requirements.  In addition, the IRB or IEC must approve all 
advertising used to recruit subjects for the study.  The protocol must be re-approved by the IRB or 
IEC upon receipt of amendments and annually, as local regulations require. 
The Principal Investigator is also responsible for providing the IRB with reports of any reportable 
serious adverse drug reactions from any other study conducted with the investigational product. 
The Sponsor will provide this information to the Principal Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB or 
IEC according to local regulations and guidelines. 
14.2. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/GCP, applicable regulatory requirements and 
corporate policy on Ethical Standards (Appendix G). 
14.3. 
Written Informed Consent 
The Principal Investigator(s) at each center will ensure that the subject is given full and adequate 
oral and written information about the nature, purpose, possible risk and benefit of the study.  
Subjects must also be notified that they are free to discontinue from the study at any time.  The 
subject should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The subject’s signed and dated informed consent must be obtained before conducting any study 
procedures. 
The Principal Investigator(s) must maintain the original, signed ICD.  A copy of the signed ICD 
must be given to the subject. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
87 
November 11, 2022 
 
Amendment 2 
 
 
15. 
DATA HANDLING AND RECORDKEEPING 
15.1. 
Health Insurance Portability Accountability Act of 1996 
The investigator agrees to comply with all applicable federal, state, and local laws and regulations 
relating to the privacy of subject health information, including, but not limited to, the Standards 
for Individually Identifiable Health Information, 45 CFR. Parts 160 and 164 (the Health Insurance 
Portability Accountability Act of 1996 [HIPAA] Privacy Regulation). The investigator shall 
ensure that study subjects authorize the use and disclosure of protected health information in 
accordance with HIPAA Privacy Regulation and in a form satisfactory to the Sponsor.  
15.2. 
Financial Disclosure 
The investigator shall provide to the Sponsor sufficient accurate financial information to allow the 
Sponsor to submit complete and accurate financial certification or disclosure statements to the 
FDA. The investigator shall promptly update this information yearly and for one year following 
completion of the study. 
15.3. 
Inspection of Records 
The Sponsor, or Sponsor’ representatives, will be allowed to conduct site visits to the investigation 
facilities for the purpose of monitoring any aspect of the study. The Investigator agrees to allow 
the monitor to inspect the drug storage area, study drug stocks, drug accountability records, subject 
charts and study source documents, and other records relative to study conduct. 
15.4. 
Access to Original Records 
It is an expectation of regulatory authorities that monitors, auditors, and representatives of national 
and international government regulatory agency bodies have access to original source 
documentation to ensure data integrity. “Original” in this context is defined as the first 
documentation of an observation and does not differentiate between hard copy and electronic 
records. 
15.5. 
Retention of Records 
Study-related records must be retained for at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing applications 
in an ICH region, or at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational product. These documents should be retained for a longer 
period, however, if required by applicable regulatory requirements or by an agreement with the 
Sponsor. 
The investigator must not destroy any study-related records without receiving approval from the 
Sponsor. The investigator must notify the Sponsor in the event of accidental loss or destruction of 
any study records. If the investigator leaves the institution where the study was conducted, the 
Sponsor must be contacted to arrange alternative record storage options. 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
88 
November 11, 2022 
 
Amendment 2 
 
 
16. 
LIST OF REFERENCES 
 
1. Alejandro J, Fidalgo P, Roda D, Roselló S, Rodríguez-Braun E, Cervantes A. Aurora 
kinase inhibitors: a new class of drugs targeting the regulatory mitotic system. Clin Transl 
Oncol. 2009;11:787-798.  
2. Ogawa E, Takenaka K, Katakura H, et al. Perimembrane Aurora-A expression is a 
significant prognostic factor in correlation with proliferative activity in non-small-cell lung 
cancer (NSCLC). Ann Surg Oncol. 2008;15(2):547-554.  
3. Mountzios G, Terpos E, Dimopoulos M-A. Aurora kinases as targets for cancer therapy. 
Cancer Treat Rev. 2008;34;175-182.  
4. Lee HJ, Koh ES, Kwak JJ, Kim HK, Park S-M, Choi I-H. Clinicopathologic significance 
of Aurora kinase A expression in non-small cell lung cancer. Basic Appl Pathol. 2012;5:8-
14. 
5. Xu HT, Lin Ma, Feng-Jie Qi, et al. Expression of serine threonine kinase 15 is associated 
with poor differentiation in lung squamous cell carcinoma and adenocarcinoma. Pathol Int. 
2006;56:375-380.  
6. Nadler Y, Camp RL, Schwartz C, et al. Expression of Aurora A (but not Aurora B) is 
predictive of survival in breast cancer. Clin Cancer Res. 2008;14:4455-4462.  
7. Lassmann S, Shen Y, Jutting U, et al. Predictive value of Aurora-A/STK15 expression for 
late-stage epithelial ovarian cancer patients treated by adjuvant chemotherapy. Clin Cancer 
Res. 2007;13(14):4083-91.  
8. Reiter R, Gais P, Jutting U, et al. Aurora kinase A messenger RNA overexpression is 
correlated with tumor progression and shortened survival in head and neck squamous cell 
carcinoma. Clin Cancer Res. 2006;12:5136-5141.  
9. Lagarde P, Perot G, Kauffmann A, et al. Mitotic checkpoints and chromosome instability 
are strong predictors of clinical outcome in gastrointestinal stromal tumors. Clin Cancer 
Res. 2012;18:826-838.  
10. Anand S, Penrhyn-Lowe S, Venkitaraman AR. AURORA-A amplification overrides the 
mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell. 2003;3:51- 
62.  
11. McGrogan BT, Gilmartin B, Desmond N, Carney DN, McCann A. Taxanes, microtubules 
and chemoresistant breast cancer. Biochim Biophys Acta. 2008;1785:96-132.  
12. VIC-1911 Investigator’s Brochure, Edition 6.0, April 2022. 
13. Lee JW, Kim S, Yang Y, et al. Aurora A kinase inhibition with VIC-1911 overcomes 
intrinsic and acquired resistance to KRASG12C inhibition in KRAS(G12C)-mutated lung 
cancer. AACR- NCI-EORTC 2021, P078. 
14. Li A, Xu W. In vivo anti-tumor efficacy study of VIC-1911 combined with AMG 510 in a 
mouse xenograft model of NCI-H358. Research Report R-JSI-P20210331, 2021. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
89 
November 11, 2022 
 
Amendment 2 
 
 
15. Data on file, VITRAC Therapeutics, LLC. 
16. NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. Version 
6.2021. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf 
17. Burns TF, Borghaei H, Ramalingam SS, et al. Targeting KRAS-mutant non–small cell lung 
cancer: One mutation at a time, with a focus on KRAS G12C Mutations. J Clin Onc. 
2020;38:4208-4218.  
18. Addeo A, Banna GL, Friedlaender A. KRAS G12C mutations in NSCLC: From target to 
resistance. Cancers. 2021;13:2541-2555. 
19. Jiao D, Yang S. Overcoming resistance to drugs targeting KRASG12C mutation. Innovation. 
2020;1:100035-100045. 
20. Janes MR, Zhang J, Li LS, et al. Targeting KRAS mutant cancers with a covalent G12C-
specific inhibitor. Cell. 2018;172:578-589.e17 
21. Fakih M, O’Neil B, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Rasmussen E, 
Morrow PKH, Ngang J, Henary HA, Hong DS. Phase I study evaluating the safety, 
tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule 
KRASG12C inhibitor, in advanced solid tumors [Abstract]. J Clin Oncol. 2019;37, no. 
15_suppl. 
22. Caruso C. AMG 510 First to inhibit “Undruggable” KRAS. Cancer Discov. 2019;9(8):988-
989. 
23. LumakrasTM (sotorasib) U.S. Product Label, 2021. 
24. Skoulidis F, Li BT, Dy GK, et al. Sotorasib for lung cancers with KRAS p.G12C mutation. 
N Engl J Med. 2021;384:2371-2381. 
25. Xue JY, Zhao Y, Aronowitz J, et al: Rapid non-uniform adaptation to conformation-
specific KRAS(G12C) inhibition. Nature. 2020;577:421-425. 
26. Awad MM, Liu S, Rybkin II, et al. Acquired resistance to KRASG12C inhibition in cancer. 
N Engl J Med. 2021;384:2382-2393. 
27. Robbrecht DGJ, Lopez J, Calvo E, He X, Hirai H, Soni N, Cook N, Dowlati A, Fascolo A, 
Moreno V, Eskens FALM, de Bono SJ. A first-in-human Phase 1 and pharmacological 
study of TAS-119, a novel selective Aurora A kinase inhibitor in patients with advanced 
solid tumours. Br J Canc. 2021;124:391-398.  
28. Falchook G, Kurzrock R, Gow L, Hong D, McGregor KA, Zhou X, Shi H, Fingert H, 
Sharma S. Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an enteric-
coated tablet formulation in non-hematologic malignancies: Phase 1 dose-escalation study. 
Invest New Drugs. 2014;32(6):1181-1187. 
29. Melichar B, Adenis A, Lockhart AC, Bennouna J, Dees C, Kayaleh O, Obermannova R, 
DeMichele A, Zatloukal P, Zhang B, Ullman CD, Schusterbauer C. Safety and activity of 
alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-
cell lung cancer, non-small cell lung cancer, head and neck squamous cell carcinoma, and 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
90 
November 11, 2022 
 
Amendment 2 
 
 
gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. The Lancet. 
2015;16(4):395-405. 
30. Simon R. Optimal two-stage designs for Phase II clinical trials. Controlled Clinical Trials. 
1989;10:1-10. 
31. Guidance for Industry, Drug-Induced Liver Injury: Premarketing Clinical Evaluation. Final 
Guidance, July 2009.  
32. Ivanova A, Qaqish BF, Schell MJ. Continuous Toxicity Monitoring in Phase II Trials in 
Oncology. Biometrics. 2005;61:540-545. 
33. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, 
Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe 
D, Verweij J. New response evaluation criteria in solid tumors: Revised RECIST guideline 
(version 1.1). E Jour Cancer. 2009;45:228-247. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
91 
November 11, 2022 
 
Amendment 2 
 
 
APPENDIX A. EASTERN COOPERATIVE GROUP (ECOG) 
PERFORMANCE STATUS SCALE 
 
ECOG PERFORMANCE STATUS* 
Grad
e
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, e.g., light housework, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about 
more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 
5 
Dead 
* From ECOG, Robert Comis, MD, Group Chair 
 
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, 
P.P.: Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin 
Oncol 5:649-655, 1982. 
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
92 
November 11, 2022 
 
Amendment 2 
 
 
APPENDIX B. COCKCROFT-GAULT FORMULA FOR CALCULATION 
OF CREATININE CLEARANCE 
Creatinine clearance must either be measured or estimated using the Cockroft-Gault formula, as 
outlined below. 
 
* Cockcroft DW, Gault MH.  Prediction of creatinine clearance from serum creatinine. Nephron. 
1976;16(1):31-41. 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
93 
November 11, 2022 
 
Amendment 2 
 
 
APPENDIX C. NEW YORK HEART ASSOCIATION (NYCA) 
CLASSIFICATION FOR HEART FAILURE – THE 
STAGES OF HEART FAILURE 
Class 
Patient Symptoms 
Class I (Mild) 
No limitation of physical activity. Ordinary physical activity does not cause 
undue fatigue, palpitation, or dyspnea (shortness of breath). 
Class II (Mild) 
Slight limitation of physical activity. Comfortable at rest, but ordinary physical 
activity results in fatigue, palpitation, or dyspnea. 
Class III (Moderate) 
Marked limitation of physical activity. Comfortable at rest, but less than 
ordinary activity causes fatigue, palpitation, or dyspnea. 
Class IV (Severe) 
Unable to carry out any physical activity without discomfort. Symptoms of 
cardiac insufficiency at rest. If any physical activity is undertaken, discomfort 
is increased. 
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
94 
November 11, 2022 
 
Amendment 2 
 
 
APPENDIX D. SCHEDULE OF STUDY PROCEDURES 
 
Study Activity 
Screeninga 
Treatment Cycle 1  
Treatment Cycles 2 and 3 
Treatment  
Cycles 4+ 
Progression 
or Relapse 
End of 
Treatmentw 
Long-Term 
Follow-Upx 
Day 1s 
Day 15t 
Day 1u 
Day 15t 
End of 
Cycle 2v 
Day 1u 
End of 
Cycle 4v 
 
 
 
Signed ICD 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
X 
X 
 
Xb 
 
 
Xb 
 
 
X 
 
Vital Signs 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
ECOG Performance Status 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
Height  
X 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
X 
 
 
X 
 
 
X 
 
Hematologyc 
X 
X 
X 
X 
X 
 
X 
 
 
X 
 
Coagulation Parametersd 
X 
X 
X 
X 
X 
 
X 
 
 
X 
 
Serum Chemistrye 
X 
X 
X 
X 
X 
 
X 
 
 
X 
 
Urinalysisf 
X 
X 
 
X 
 
 
X 
 
 
X 
 
Beta-hCG for WCBP 
X 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
Xg 
Xg 
 
 
 
 
 
 
X 
 
Ophthalmologic 
Examinationh 
X 
 
 
 
 
 
 
 
 
X 
 
Concomitant Medications 
X 
Continuous 
 
AE Assessment 
 
Continuous 
 
Tumor sample 
Xi 
 
 
Xo 
 
 
 
 
Xo 
 
 
Disease Assessmentj 
X 
 
 
 
 
X 
 
X 
X 
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
95 
November 11, 2022 
 
Amendment 2 
 
 
Study Activity 
Screeninga 
Treatment Cycle 1  
Treatment Cycles 2 and 3 
Treatment  
Cycles 4+ 
Progression 
or Relapse 
End of 
Treatmentw 
Long-Term 
Follow-Upx 
Day 1s 
Day 15t 
Day 1u 
Day 15t 
End of 
Cycle 2v 
Day 1u 
End of 
Cycle 4v 
 
 
 
Peripheral Blood for PK 
Assessmentk 
 
X 
X 
Xl 
 
 
Xm 
 
 
 
 
Peripheral Blood for 
Pharmacodynamic 
Assessmentn 
 
X 
 
 
 
 
 
 
X 
 
 
VIC-1911 Dosingp 
 
b.i.d. according to dose regimen 
 
 
 
Sotorasib Dosingq 
 
q.d. according to dose regimen  
 
 
 
VIC-1911 and Sotorasib 
Dosing Diariesr 
 
X 
X 
X 
X 
 
X 
 
 
X 
 
Survival Assessment  
 
Continuous 
 
a Screening to be performed within 28 days of Cycle 1, Day 1 
b Abbreviated physical exam 
c Hematology parameters collected at Screening, Cycle 1 Day 1 (only if not performed in the previous 72 hours), Day 15 for the first 3 cycles, Day 1 of each 
subsequent cycle (within 3 days prior to Day 1 of each subsequent cycle) and End of Treatment. See Table 12 for tests to be conducted at each time point. 
d Coagulation parameters collected at Screening, Cycle 1 Day 1 (only if not performed within the previous 72 hours), Day 15 for the first 3 cycles, Day 1 of each 
subsequent cycle (within 3 days prior to Day 1 of each subsequent cycle) and End of Treatment. See Table 12 for tests to be conducted at each time point. 
e Serum chemistry collected at Screening, Cycle 1 Day 1 (only if not performed within the previous 72 hours), Day 15 for the first 3 cycles, Day 1 of each 
subsequent cycle (within 3 days prior to Day 1 of each subsequent cycle) and End of Treatment. See Table 12 for tests to be conducted at each time point.  
f Urinalysis performed at Screening, Cycle 1 Day 1 (only if not performed in the previous 72 hours), Day 1 of each subsequent cycle (within 3 days prior to Day 
1 of each subsequent cycle) and End of Treatment. See Table 12 for tests to be conducted at each time point. 
g ECGs performed pre-dose and approximately 2 hours post-dose (following first daily dose only), Cycle 1 Day 1 and Day 15 
h Ophthalmologic tests performed within 28 days of Cycle 1 Day 1, End of Treatment and as clinically indicated throughout the study. See Section 10.2.5 for 
tests to be conducted at these visits. 
i Archived, or if clinically feasible, fresh biopsy, for pharmacodynamic assessment at Screening 
j Disease Assessment may include CT, MRI, and/or physical exam. Should be performed every 8 weeks (± 7 days) 
k Peripheral blood collected in EDTA for PK assessment Cycle 1 Day 1 and Day 15 pre-dose, at 15 and 30 minutes (± 5 minutes), 1 hour (± 15 minutes), 2 and 4 
hours (± 30 minutes), 8 hours (± 1 hour) and 24 hours (± 2 hours) following the first daily dose, and pre-first dose Cycle 2, 4, 6 (Dose Escalation Phase only). 
l Pre-first dose C2 only 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
96 
November 11, 2022 
 
Amendment 2 
 
 
m Pre-first dose C4 and C6 only  
n Peripheral blood collected in EDTA for pharmacodynamic assessment pre-dose C1D1 and at progression of disease (Expansion Phase Cohorts 2b and 2c only) 
o Fresh biopsy pre-first dose C3 only and relapse/progression, if clinically feasible (Expansion Phase only) 
p VIC-1911 dose orally twice daily, per assigned dose regimen. Provide VIC-1911 Dosing Diary. Withhold the evening dose on C1D1 and C1D15. On C1D2 and 
C1D16, delay the morning dose until completion of the Cycle 1 Day 1 and Day 15 24-hour post-first-dose blood draw. 
q Sotorasib dose orally once daily, continuously. Provide VIC-1911 Plus Sotorasib Dosing Diary. On C1D2 and C1D16, delay the morning dose until completion 
of the Cycle 1 Day 1 and Day 15 24-hour post-first-dose blood draw. 
r Review VIC-1911 and VIC-1911 Plus Sotorasib Dosing Diaries with subject (each clinic visit + End of Treatment).  
s Day 1 PE, vital signs, weight, ECOG performance status, pre-dose ECG may be completed within 24 hours prior to C1D1.  
t Day 15 (±1 day) 
u Day 1 (within 3 days prior to Day 1 of each cycle) 
v Day 28 (±7 days) 
w End of Treatment visit should be 28 days from last dose of study medication (±5 days) 
x Long-term follow-up for 6 months consists of clinic visits or telephone calls every 3 months to assess survival status 
 
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
97 
November 11, 2022 
 
Amendment 2 
 
 
APPENDIX E. RESPONSE EVALUATION CRITERIA IN SOLID 
TUMORS (RECIST 1.1)33  
1. Measurability of Tumor at Baseline 
1.1 Definitions 
At baseline, tumor lesions/lymph nodes will be categorized measurable or non-measurable as 
follows: 
1.1.1. Measurable 
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of: 
• 10mm by CT scan (CT scan slice thickness no greater than 5 mm) 
• 10mm caliper measurement by clinical exam (lesions which cannot be accurately 
measured with calipers should be recorded as non-measurable) 
• 20mm by chest X-ray 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph 
node must be ≥ 15mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis 
will be measured and followed. See also notes below on ‘Baseline documentation of target and 
non-target lesions’ for information on lymph node measurement. 
1.1.2. Non-measurable 
All other lesions, including small lesions (longest diameter <10mm or pathological lymph 
nodes with ≥ 10 to < 15mm short axis) as well as truly non-measurable lesions. Lesions 
considered truly non-measurable include: leptomeningeal disease, ascites, pleural or 
pericardial effusion, inflammatory breast disease, lymphangitic involvement of skin or lung, 
abdominal masses/abdominal organomegaly identified by physical exam that is not measurable 
by reproducible imaging techniques. 
1.1.3. Special considerations regarding lesion measurability 
Bone lesions, cystic lesions, and lesions previously treated with local therapy require particular 
comment: 
Bone lesions: 
• Bone scan, PET scan or plain films are not considered adequate imaging techniques to 
measure bone lesions. However, these techniques can be used to confirm the presence 
or disappearance of bone lesions. 
• Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue 
components, that can be evaluated by cross sectional imaging techniques such as CT 
or MRI can be considered as measurable lesions if the soft tissue component meets the 
definition of measurability described above. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
98 
November 11, 2022 
 
Amendment 2 
 
 
• Blastic bone lesions are non-measurable. 
Cystic lesions: 
• Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they 
are, by definition, simple cysts. 
• ‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above. However, if 
noncystic lesions are present in the same patient, these are preferred for selection as 
target lesions. 
Lesions with prior local treatment: 
• Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
loco-regional therapy, are usually not considered measurable unless there has been 
demonstrated progression in the lesion. Study protocols should detail the conditions 
under which such lesions would be considered measurable. 
1.2. Specifications by methods of measurements 
1.2.1. Measurement of lesions 
All measurements should be recorded in metric notation, using calipers if clinically assessed. 
All baseline evaluations should be performed as close as possible to the treatment start and 
never more than 4 weeks before the beginning of the treatment. 
1.2.2. Method of assessment 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging based evaluation 
should always be done rather than clinical examination unless the lesion(s) being followed 
cannot be imaged but are assessable by clinical exam. 
Clinical lesions: Clinical lesions will only be considered measurable when they are superficial 
and P10mm diameter as assessed using calipers (e.g. skin nodules). For the case of skin lesions, 
documentation by color photography including a ruler to estimate the size of the lesion is 
suggested. As noted above, when lesions can be evaluated by both clinical exam and imaging, 
imaging evaluation should be undertaken since it is more objective and may also be reviewed 
at the end of the study. 
Chest X-ray: Chest CT is preferred over chest X-ray, particularly when progression is an 
important endpoint, since CT is more sensitive than X-ray, particularly in identifying new 
lesions. However, lesions on chest X-ray may be considered measurable if they are clearly 
defined and surrounded by aerated lung.  
CT, MRI: CT is the best currently available and reproducible method to measure lesions 
selected for response assessment. This guideline has defined measurability of lesions on CT 
scan based on the assumption that CT slice thickness is 5mm or less. When CT scans have 
slice thickness greater than 5 mm, the minimum size for a measurable lesion should be twice 
the slice thickness. MRI is also acceptable in certain situations (e.g., for body scans). More 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
99 
November 11, 2022 
 
Amendment 2 
 
 
details concerning the use of both CT and MRI for assessment of objective tumour response 
evaluation are provided in Appendix II of the paper. 
Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement. Ultrasound examinations cannot be reproduced in their entirety for 
independent review at a later date and, because they are operator dependent, it cannot be 
guaranteed that the same technique and measurements will be taken from one assessment to 
the next. If new lesions are identified by ultrasound in the course of the study, confirmation by 
CT or MRI is advised. If there is concern about radiation exposure at CT, MRI may be used 
instead of CT in selected instances. 
Endoscopy, laparoscopy: The utilization of these techniques for objective tumor evaluation 
is not advised. However, they can be useful to confirm complete pathological response when 
biopsies are obtained or to determine relapse in trials where recurrence following complete 
response or surgical resection is an endpoint. 
Tumor markers: Tumor markers alone cannot be used to assess objective tumor response. If 
markers are initially above the upper normal limit, however, they must normalize for a patient 
to be considered in complete response. Because tumor markers are disease specific, 
instructions for their measurement should be incorporated into protocols on a disease specific 
basis. Specific guidelines for both CA-125 response (in recurrent ovarian cancer) and PSA 
response (in recurrent prostate cancer), have been published. In addition, the Gynecologic 
Cancer Intergroup has developed CA125 progression criteria which are to be integrated with 
objective tumor assessment for use in first-line trials in ovarian cancer. 
Cytology, histology: These techniques can be used to differentiate between PR and CR in rare 
cases if required by protocol (for example, residual lesions in tumor types such as germ cell 
tumors, where known residual benign tumors can remain). When effusions are known to be a 
potential adverse effect of treatment (e.g. with certain taxane compounds or angiogenesis 
inhibitors), the cytological confirmation of the neoplastic origin of any effusion that appears 
or worsens during treatment can be considered if the measurable tumor has met criteria for 
response or stable disease in order to differentiate between response (or stable disease) and 
progressive disease. 
2. Tumor response evaluation 
2.1. Assessment of overall tumor burden and measurable disease 
To assess objective response or future progression, it is necessary to estimate the overall tumor 
burden at baseline and use this as a comparator for subsequent measurements. Only patients 
with measurable disease at baseline should be included in protocols where objective tumor 
response is the primary endpoint. Measurable disease is defined by the presence of at least one 
measurable lesion (as detailed above in Section 1). In studies where the primary endpoint is 
tumor progression (either time to progression or proportion with progression at a fixed date), 
the protocol must specify if entry is restricted to those with measurable disease or whether 
patients having non-measurable disease only are also eligible. 
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
100 
November 11, 2022 
 
Amendment 2 
 
 
2.2. Baseline documentation of ‘target’ and ‘non-target’ lesions 
When more than one measurable lesion is present at baseline all lesions up to a maximum of 
five lesions total (and a maximum of two lesions per organ) representative of all involved 
organs should be identified as target lesions and will be recorded and measured at baseline 
(this means in instances where patients have only one or two organ sites involved a maximum 
of two and four lesions respectively will be recorded). For evidence to support the selection of 
only five target lesions, see analyses on a large prospective database in the article by Bogaerts 
J, et al, Eur Jour Cancer,2009;45:248-260. 
Target lesions should be selected on the basis of their size (lesions with the longest diameter), 
be representative of all involved organs, but in addition should be those that lend themselves 
to reproducible repeated measurements. It may be the case that, on occasion, the largest lesion 
does not lend itself to reproducible measurement in which circumstance the next largest lesion 
which can be measured reproducibly should be selected.  
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. As noted in Section 1, pathological nodes 
which are defined as measurable and may be identified as target lesions must meet the criterion 
of a short axis of ≥ 15mm by CT scan. Only the short axis of these nodes will contribute to the 
baseline sum. The short axis of the node is the diameter normally used by radiologists to judge 
if a node is involved by solid tumor. Nodal size is normally reported as two dimensions in the 
plane in which the image is obtained (for CT scan this is almost always the axial plane; for 
MRI the plane of acquisition may be axial, sagittal or coronal). The smaller of these measures 
is the short axis. For example, an abdominal node which is reported as being 20mm· 30mm 
has a short axis of 20mm and qualifies as a malignant, measurable node. In this example, 20mm 
should be recorded as the node measurement. All other pathological nodes (those with short 
axis ≥ 10mm but <15 mm) should be considered non-target lesions. Nodes that have a short 
axis <10mm are considered non-pathological and should not be recorded or followed. 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression 
in the measurable dimension of the disease. 
All other lesions (or sites of disease) including pathological lymph nodes should be identified 
as non-target lesions and should also be recorded at baseline. Measurements are not required 
and these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal 
progression’. In addition, it is possible to record multiple nontarget lesions involving the same 
organ as a single item on the case record form (e.g. ‘multiple enlarged pelvic lymph nodes’ or 
‘multiple liver metastases’). 
 
 
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
101 
November 11, 2022 
 
Amendment 2 
 
 
2.3. Response criteria 
This section provides the definitions of the criteria used to determine objective tumor response 
for target lesions.  
2.3.1. Evaluation of target lesions 
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm. 
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking 
as reference the baseline sum diameters. 
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate 
an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also 
considered progression). 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study. 
2.3.2. Special notes on the assessment of target lesions 
Lymph nodes. Lymph nodes identified as target lesions should always have the actual short 
axis measurement recorded (measured in the same anatomical plane as the baseline 
examination), even if the nodes regress to below 10mm on study. This means that when lymph 
nodes are included as target lesions, the ‘sum’ of lesions may not be zero even if complete 
response criteria are met, since a normal lymph node is defined as having a short axis of 
<10mm. Case report forms or other data collection methods may therefore be designed to have 
target nodal lesions recorded in a separate section where, in order to qualify for CR, each node 
must achieve a short axis <10mm. For PR, SD and PD, the actual short axis measurement of 
the nodes is to be included in the sum of target lesions.  
Target lesions that become ‘too small to measure’. While on study, all lesions (nodal and non-
nodal) recorded at baseline should have their actual measurements recorded at each subsequent 
evaluation, even when very small (e.g., 2mm). However, sometimes lesions or lymph nodes 
which are recorded as target lesions at baseline become so faint on CT scan that the radiologist 
may not feel comfortable assigning an exact measure and may report themas being ‘too small 
to measure’. When this occurs, it is important that a value be recorded on the case report form. 
If it is the opinion of the radiologist that the lesion has likely disappeared, the measurement 
should be recorded as 0mm. If the lesion is believed to be present and is faintly seen but too 
small to measure, a default value of 5mm should be assigned (Note: It is less likely that this 
rule will be used for lymph nodes since they usually have a definable size when normal and 
are frequently surrounded by fat such as in the retroperitoneum; however, if a lymph node is 
believed to be present and is faintly seen but too small to measure, a default value of 5 mm 
should be assigned in this circumstance as well). This default value is derived from the 5mm 
CT slice thickness (but should not be changed with varying CT slice thickness). The 
measurement of these lesions is potentially non-reproducible, therefore providing this default 
value will prevent false responses or progressions based upon measurement error. To reiterate, 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
102 
November 11, 2022 
 
Amendment 2 
 
 
however, if the radiologist is able to provide an actual measure, that should be recorded, even 
if it is below 5mm. 
Lesions that split or coalesce on treatment. As noted in Appendix II of the paper, when non-
nodal lesions ‘fragment’, the longest diameters of the fragmented portions should be added 
together to calculate the target lesion sum. Similarly, as lesions coalesce, a plane between them 
may be maintained that would aid in individual lesion. If the lesions have truly coalesced such 
that they are no longer separable, the vector of the longest diameter in this instance should be 
the maximal longest diameter for the ‘coalesced lesion’. 
2.3.3. Evaluation of non-target lesions 
This section provides the definitions of the criteria used to determine the tumor response for 
the group of non-target lesions. While some non-target lesions may actually be measurable, 
they need not be measured and instead should be assessed only qualitatively at the time points 
specified in the protocol. 
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor 
marker level. All lymph nodes must be non-pathological in size (<10mm short axis). 
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits. 
Progressive Disease (PD): Unequivocal progression (see comments below) of existing non-
target lesions. (Note: the appearance of one or more new lesions is also considered 
progression). 
2.3.4. Special notes on assessment of progression of nontarget disease 
The concept of progression of non-target disease requires additional explanation as follows:  
When the patient also has measurable disease. In this setting, to achieve ‘unequivocal 
progression’ on the basis of the non-target disease, there must be an overall level of substantial 
worsening in non-target disease such that, even in presence of SD or PR in target disease, the 
overall tumor burden has increased sufficiently to merit discontinuation of therapy. A modest 
‘increase’ in the size of one or more non-target lesions is usually not sufficient to quality for 
unequivocal progression status. The designation of overall progression solely on the basis of 
change in non-target disease in the face of SD or PR of target disease will therefore be 
extremely rare. 
When the patient has only non-measurable disease. This circumstance arises in some Phase III 
trials when it is not a criterion of study entry to have measurable disease. The same general 
concepts apply here as noted above, however, in this instance there is no measurable disease 
assessment to factor into the interpretation of an increase in non-measurable disease burden. 
Because worsening in non-target disease cannot be easily quantified (by definition: if all 
lesions are truly non-measurable) a useful test that can be applied when assessing patients for 
unequivocal progression is to consider if the increase in overall disease burden based on the 
change in non-measurable disease is comparable in magnitude to the increase that would be 
required to declare PD for measurable disease: i.e., an increase in tumor burden representing 
an additional 73% increase in ‘volume’ (which is equivalent to a 20% increase diameter in a 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
103 
November 11, 2022 
 
Amendment 2 
 
 
measurable lesion). Examples include an increase in a pleural effusion from ‘trace’ to ‘large’, 
an increase in lymphangitic protocols as ‘sufficient to require a change in therapy’. If 
‘unequivocal progression’ is seen, the patient should be considered to have had overall PD at 
that point. While it would be ideal to have objective criteria to apply to non-measurable disease, 
the very nature of that disease makes it impossible to do so, therefore the increase must be 
substantial. 
2.3.5. New lesions 
The appearance of new malignant lesions denotes disease progression; therefore, some 
comments on detection of new lesions are important. There are no specific criteria for the 
identification of new radiographic lesions; however, the finding of a new lesion should be 
unequivocal: i.e., not attributable to differences in scanning technique, change in imaging 
modality or findings thought to represent something other than tumor (for example, some 
‘new’ bone lesions may be simply healing or flare of pre-existing lesions). This is particularly 
important when the patient’s baseline lesions show partial or complete response. For example, 
necrosis of a liver lesion may be reported on a CT scan report as a ‘new’ cystic lesion, which 
it is not. 
A lesion identified on a follow-up study in an anatomical location that was not scanned at 
baseline is considered a new lesion and will indicate disease progression. An example of this 
is the patient who has visceral disease at baseline and while on study has a CT or MRI brain 
ordered which reveals metastases. The patient’s brain metastases are considered to be evidence 
of PD even if he/she did not have brain imaging at baseline. 
If a new lesion is equivocal, for example because of its small size, continued therapy and 
follow-up evaluation will clarify if it represents truly new disease. If repeat scans confirm there 
is definitely a new lesion, then progression should be declared using the date of the initial scan.  
While FDG-PET response assessments need additional study, it is sometimes reasonable to 
incorporate the use of FDG-PET scanning to complement CT scanning in assessment of 
progression (particularly possible ‘new’ disease). New lesions on the basis of FDG-PET 
imaging can be identified according to the following algorithm: 
a. Negative FDG-PET at baseline, with a positive FDG-PET (=FDG avid with an uptake 
greater than twice that of the surrounding tissue on the attenuation corrected image) at 
follow-up is a sign of PD based on a new lesion. 
b. No FDG-PET at baseline and a positive FDG-PET at follow- up: 
• If the positive FDG-PET at follow-up corresponds to a new site of disease 
confirmed by CT, this is PD.  
• If the positive FDG-PET at follow-up is not confirmed as a new site of disease on 
CT, additional follow-up CT scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial abnormal FDG-
PET scan).  
• If the positive FDG-PET at follow-up corresponds to a pre-existing site of disease 
on CT that is not progressing on the basis of the anatomic images, this is not PD.  


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
104 
November 11, 2022 
 
Amendment 2 
 
 
2.4. Evaluation of best overall response 
The best overall response is the best response recorded from the start of the study treatment 
until the end of treatment taking into account any requirement for confirmation. On occasion 
a response may not be documented until after the end of therapy so protocols should be clear 
if post-treatment assessments are to be considered in determination of best overall response. 
Protocols must specify how any new therapy introduced before progression will affect best 
response designation. The patient’s best overall response assignment will depend on the 
findings of both target and non-target disease and will also take into consideration the 
appearance of new lesions. Furthermore, depending on the nature of the study and the protocol 
requirements, it may also require confirmatory measurement (See Section 1.6). Specifically, 
in non-randomized trials where response is the primary endpoint, confirmation of PR or CR is 
needed to deem either one the ‘best overall response’. This is described further below. 
2.4.1. Time point response 
It is assumed that at each protocol specified time point, a response assessment occurs. Table 1 
provides a summary of the overall response status calculation at each time point for patients 
who have measurable disease at baseline. 
When patients have non-measurable (therefore non-target) disease only, Table 2 is to be used. 
Table 1: Criteria for Overall Response for Target (+/- Non-target) Disease 
 
 
 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all evaluated 
No 
PR 
SD 
Non-PD or not all evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
CR = complete response, PR= partial response, SD=stable disease, PD= progressive disease, NE=inevaluable 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
105 
November 11, 2022 
 
Amendment 2 
 
 
Table 2: Criteria for Overall Response for Non-target Disease Only 
2.4.2. Missing assessments and inevaluable designation 
When no imaging/measurement is done at all at a particular time point, the patient is not 
evaluable (NE) at that time point. If only a subset of lesion measurements are made at an 
assessment, usually the case is also considered NE at that time point, unless a convincing 
argument can be made that the contribution of the individual missing lesion(s) would not 
change the assigned time point response. This would be most likely to happen in the case of 
PD. For example, if a patient had a baseline sum of 50mm with three measured lesions and at 
follow-up only two lesions were assessed, but those gave a sum of 80 mm, the patient will 
have achieved PD status, regardless of the contribution of the missing lesion. 
2.4.3. Best overall response: all time points 
The best overall response is determined once all the data for the patient is known.  
Best response determination in trials where confirmation of complete or partial response IS 
NOT required: Best response in these trials is defined as the best response across all time points 
(for example, a patient who has SD at first assessment, PR at second assessment, and PD on 
last assessment has a best overall response of PR). When SD is believed to be best response, it 
must also meet the protocol specified minimum time from baseline. If the minimum time is 
not met when SD is otherwise the best time point response, the patient’s best response depends 
on the subsequent assessments. For example, a patient who has SD at first assessment, PD at 
second and does not meet minimum duration for SD, will have a best response of PD. The 
same patient lost to follow-up after the first SD assessment would be considered inevaluable. 
Best response determination in trials where confirmation of complete or partial response IS 
required: Complete or partial responses may be claimed only if the criteria for each are met at 
a subsequent time point as specified in the protocol (generally 4 weeks later). In this 
circumstance, the best overall response can be interpreted as in Table 3. 
 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
CR = complete response, PR= partial response, SD=stable disease, PD= progressive disease, NE=inevaluable 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
106 
November 11, 2022 
 
Amendment 2 
 
 
Table 3: Best Overall Response When Confirmation of CR and PR is Required 
2.4.4. Special notes on response assessment 
When nodal disease is included in the sum of target lesions and the nodes decrease to ‘normal’ 
size (<10 mm), they may still have a measurement reported on scans. This measurement should 
be recorded even though the nodes are normal in order not to overstate progression should it 
be based on increase in size of the nodes. As noted earlier, this means that patients with CR 
may not have a total sum of ‘zero’ on the case report form (CRF).  
In trials where confirmation of response is required, repeated ‘NE’ time point assessments may 
complicate best response determination. The analysis plan for the trial must address how 
missing data/assessments will be addressed in determination of response and progression. For 
example, in most trials it is reasonable to consider a patient with time point responses of PR-
NE-PR as a confirmed response.  
Overall Response First 
Time Point 
Overall Response 
Subsequent Time Point 
BEST Overall Response 
CR 
CR 
CR 
CR 
PR 
SD, PD, or PRa 
CR 
SD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
CR 
PD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
CR 
NE 
SD provided minimum criteria for SD 
duration met, otherwise, NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
PR 
NE 
SD provided minimum criteria for SD 
duration met, otherwise, NE 
NE 
NE 
NE 
CR = complete response, PR= partial response, SD=stable disease, PD= progressive disease, 
NE=inevaluable 
aIf a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease 
meeting PR criteria relative to baseline, makes the disease PD at that point (since disease must have 
reappeared after CR). Best response would depend on whether minimum duration for SD was met. 
However, sometimes ‘CR’ may be claimed when subsequent scans suggest small lesions were likely still 
present and, in fact, the patient had PR, not CR at the first time point. Under these circumstances, the 
original CR should be changed to PR, and the best response is PR. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
107 
November 11, 2022 
 
Amendment 2 
 
 
Patients with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as 
‘symptomatic deterioration’. Every effort should be made to document objective progression 
even after discontinuation of treatment. Symptomatic deterioration is not a descriptor of an 
objective response: it is a reason for stopping study therapy. The objective response status of 
such patients is to be determined by evaluation of target and non-target disease as shown in 
Tables 1–3. 
Conditions that define ‘early progression, early death and inevaluability’ are study specific and 
should be clearly described in each protocol (depending on treatment duration, treatment 
periodicity). 
In some circumstances, it may be difficult to distinguish residual disease from normal tissue. 
When the evaluation of complete response depends upon this determination, it is recommended 
that the residual lesion be investigated (fine needle aspirate/biopsy) before assigning a status 
of complete response. FDG-PET may be used to upgrade a response to a CR in a manner 
similar to a biopsy in cases where a residual radiographic abnormality is thought to represent 
fibrosis or scarring. The use of FDG-PET in this circumstance should be prospectively 
described in the protocol and supported by disease specific medical literature for the indication. 
However, it must be acknowledged that both approaches may lead to false positive CR due to 
limitations of FDG-PET and biopsy resolution/ sensitivity. 
For equivocal findings of progression (e.g. very small and uncertain new lesions; cystic 
changes or necrosis in existing lesions), treatment may continue until the next scheduled 
assessment. If at the next scheduled assessment, progression is confirmed, the date of 
progression should be the earlier date when progression was suspected. 
2.5. Frequency of tumor re-evaluation 
Frequency of tumor re-evaluation while on treatment should be protocol specific and adapted 
to the type and schedule of treatment. However, in the context of phase II studies where the 
beneficial effect of therapy is not known, follow-up every 6–8 weeks (timed to coincide with 
the end of a cycle) is reasonable. Smaller or greater time intervals than these could be justified 
in specific regimens or circumstances. The protocol should specify which organ sites are to be 
evaluated at baseline (usually those most likely to be involved with metastatic disease for the 
tumor type under study) and how often evaluations are repeated. Normally, all target and non-
target sites are evaluated at each assessment. In selected circumstances, certain non-target 
organs may be evaluated less frequently. For example, bone scans may need to be repeated 
only when complete response is identified in target disease or when progression in bone is 
suspected. 
After the end of the treatment, the need for repetitive tumor evaluations depends on whether 
the trial has as a goal the response rate or the time to an event (progression/death). If ‘time to 
an event’ (e.g. time to progression, disease-free survival, progression-free survival) is the main 
endpoint of the study, then routine scheduled re-evaluation of protocol specified sites of 
disease is warranted. In randomized comparative trials in particular, the scheduled assessments 
should be performed as identified on a calendar schedule (for example: every 6–8 weeks on 
treatment or every 3–4 months after treatment) and should not be affected by delays in therapy, 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
108 
November 11, 2022 
 
Amendment 2 
 
 
drug holidays or any other events that might lead to imbalance in a treatment arm in the timing 
of disease assessment. 
2.6. Confirmatory measurement/duration of response 
2.6.1. Confirmation 
In non-randomized trials where response is the primary endpoint, confirmation of PR and CR 
is required to ensure responses identified are not the result of measurement error. This will also 
permit appropriate interpretation of results in the context of historical data where response has 
traditionally required confirmation in such trials (see Bogaerts J, et al, Eur Jour 
Cancer,2009;45:248-260). However, in all other circumstances, i.e., in randomized trials 
(phase II or III) or studies where stable disease or progression are the primary endpoints, 
confirmation of response is not required since it will not add value to the interpretation of trial 
results. However, elimination of the requirement for response confirmation may increase the 
importance of central review to protect against bias, in particular in studies which are not 
blinded. 
In the case of SD, measurements must have met the SD criteria at least once after study entry 
at a minimum interval (in general not less than 6–8 weeks) that is defined in the study protocol. 
2.6.2. Duration of overall response 
The duration of overall response is measured from the time measurement criteria are first met 
for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease 
is objectively documented (taking as reference for progressive disease the smallest 
measurements recorded on study). 
The duration of overall complete response is measured from the time measurement criteria are 
first met for CR until the first date that recurrent disease is objectively documented.  
2.6.3. Duration of stable disease 
Stable disease is measured from the start of the treatment (in randomized trials, from date of 
randomization) until the criteria for progression are met, taking as reference the smallest sum 
on study (if the baseline sum is the smallest, this is the reference for calculation of PD).  
The clinical relevance of the duration of stable disease varies in different studies and diseases. 
If the proportion of patients achieving stable disease for a minimum period of time is an 
endpoint of importance in a particular trial, the protocol should specify the minimal time 
interval required between two measurements for determination of stable disease.  
Note: The duration of response and stable disease as well as the progression-free survival are 
influenced by the frequency of follow-up after baseline evaluation. It is not in the scope of this 
guideline to define a standard follow-up frequency. The frequency should take into account 
many parameters including disease types and stages, treatment periodicity and standard 
practice. However, these limitations of the precision of the measured endpoint should be taken 
into account if comparisons between trials are to be made.  
 
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
109 
November 11, 2022 
 
Amendment 2 
 
 
2.7. Progression-free survival/proportion progression-free 
2.7.1. Phase II trials 
This guideline is focused primarily on the use of objective response endpoints for phase II 
trials. In some circumstances, ‘response rate’ may not be the optimal method to assess the 
potential anticancer activity of new agents/regimens. In such cases ‘progression-free survival’ 
(PFS) or the ‘proportion progression-free’ at landmark time points, might be considered 
appropriate alternatives to provide an initial signal of biologic effect of new agents. It is clear, 
however, that in an uncontrolled trial, these measures are subject to criticism since an 
apparently promising observation may be related to biological factors such as patient selection 
and not the impact of the intervention. Thus, phase II screening trials utilizing these endpoints 
are best designed with a randomized control. Exceptions may exist where the behavior patterns 
of certain cancers are so consistent (and usually consistently poor), that a non-randomized trial 
is justifiable. However, in these cases it will be essential to document with care the basis for 
estimating the expected PFS or proportion progression-free in the absence of a treatment effect. 
2.7.2. Phase III trials 
Phase III trials in advanced cancers are increasingly designed to evaluate progression-free 
survival or time to progression as the primary outcome of interest. Assessment of progression 
is relatively straightforward if the protocol requires all patients to have measurable disease. 
However, restricting entry to this subset of patients is subject to criticism: it may result in a 
trial where the results are less likely to be generalizable if, in the disease under study, a 
substantial proportion of patients would be excluded. Moreover, the restriction to entry will 
slow recruitment to the study. Increasingly, therefore, trials allow entry of both patients with 
measurable disease as well as those with non-measurable disease only. In this circumstance, 
care must be taken to explicitly describe the findings which would qualify for progressive 
disease for those patients without measurable lesions. Furthermore, in this setting, protocols 
must indicate if the maximum number of recorded target lesions for those patients with 
measurable disease may be relaxed from five to three. As found in the ‘special notes on 
assessment of progression’, these guidelines offer recommendations for assessment of 
progression in this setting. Furthermore, if available, validated tumor marker measures of 
progression (as has been proposed for ovarian cancer) may be useful to integrate into the 
definition of progression. Centralized blinded review of imaging studies or of source imaging 
reports to verify ‘unequivocal progression’ may be needed if important drug development or 
drug approval decisions are to be based on the study outcome. Finally, as noted earlier, because 
the date of progression is subject to ascertainment bias, timing of investigations in study arms 
should be the same. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
110 
November 11, 2022 
 
Amendment 2 
 
 
APPENDIX F. VIC-1911-01 TUMOR CORRELATIVE ANALYSIS PLAN 
Barbara Burtness, MD, Jongwoo Lee PhD, Katerina Politi, PhD 
Yale Cancer Center, Yale School of Medicine, New Haven, CT  06510 
Mutant KRAS was long considered an undruggable target due to absence of binding pockets for 
small-molecule inhibitors. Recently, covalent direct KRAS inhibitors which bind to cysteine 12 of 
the GDP-bound form of the KRAS G12C protein have been developed, and rapidly entered the 
clinic. While these represent a genuine breakthrough in management of KRAS-mutated NSCLC, 
the response rates of 37 to 45% indicate that not all KRAS G12C-mutated NSCLCs respond to 
these agents, and acquired resistance is common, with median PFS of under 7 months.  
Intrinsic resistance may be related to additional abnormalities in the MEK signaling pathway, 
while both adaptive and mutational mechanisms may underlie acquired resistance. Zhao et. al. 
describes acquired (treatment-emergent) alterations in 63% of sotorasib-treated, predominantly 
NSCLC, patients (DOI:  10.1038/s41586-021-04065-2). Secondary mutations were identified in 
KRAS, NRAS, BRAF, EGFR, FGFR2, MYC and other genes. Patient-derived xenograft and cell 
line models exhibited resistance to KRAS(G12C) inhibition when low allele frequency hotspot 
mutations in KRAS (G12V or G13D), NRAS (Q61K or G13R), MRAS (Q71R) and/or BRAF 
(G596R) were observed. Co-mutation of TP53 and KRAS, often described in NSCLC, was present 
in a subset of the patients in this study.  
Awad et. al. (DOI: 10.1056/NEJMoa2105281) conducted genomic analysis of NSCLC and 
colorectal cancer patients with acquired resistance to adagrasib, and found putative mechanisms 
of resistance in 45%, including 18% with multiple coincident mechanisms. Most commonly 
observed were secondary KRAS alterations: G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C, 
and high-level amplification of the KRASG12C allele. Acquired bypass mechanisms of resistance 
included MET amplification; activating mutations in NRAS, BRAF, MAP2K1, and RET; 
oncogenic fusions involving ALK, RET, BRAF, RAF1, and FGFR3; and loss-of-function 
mutations in NF1 and PTEN. Histologic transformation to squamous-cell carcinoma was also 
observed. Separately, acquired HER2 copy number gain has been observed in a patient with 
sotorasib resistance (DOI: 10.1016/j.ejca.2021.10.003). Single cell analyses in models of 
resistance in vitro have demonstrated adaptive resistance mediated by Aurora A and MEK 
signaling (Nature. 2020 Jan;577(7790):421-425. DOI: 10.1038/s41586-019-1884-x.) 
Baseline levels of Aurora A expression and protein stability may vary in NSCLC patients due to 
abnormalities in expression of Aurora interacting proteins. TP53 negatively regulates transcription 
of AURA kinase, and loss of TP53 typically increases the transcription of AURA kinase mRNA, 
contributing to higher cellular levels of AURA kinase protein. Further, direct physical interaction 
of AURA kinase with partner proteins regulates AURA kinase stability and expression levels. 
Prominent among these is NEDD9, a scaffolding protein that binds AURA kinase to stimulate its 
activity in mitosis and cytokinesis. Overexpression of NEDD9 promotes resistance to AURA 
kinase inhibition, based on triggering conformational changes in the AURA kianse protein, and 
induces ERK1/2, AKT, and EMT signaling.  Another AURA kinase-binding protein that increases 
both AURA kinase expression and may relate to resistance to AURA kinase inhibition is TPX2. 
A recent study of therapeutic resistance in lung cancer models determined that post-translational 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
111 
November 11, 2022 
 
Amendment 2 
 
 
activation of AURA kinase by its upregulated coactivator TPX2 contributes to adaptive (non-
genomic) resistance to EGFR inhibitors, reducing EGFR inhibitor-induced apoptosis.   
In this correlative biomarker plan, we will characterize tumor samples from patients enrolled in 
VIC-1911-01 for baseline and acquired resistance mutations, as well as differences in transcription 
and expression of Aurora A and its interacting partners, and histologic evidence of tumor 
transformation to other histological subtypes including squamous cell histology.  
Pre-treatment tumor biopsies will be obtained from all patients in whom it is safe and feasible to 
do so. Archived tissue may be substituted for fresh biopsies if not clinically feasible to obtain a 
fresh biopsy at Screening. This material will be examined by H&E. Tissue will be submitted to the 
Yale Center for Genome Analysis for WES and RNA sequencing. Immunohistochemistry for 
expression of Aurora A, phosphoAurora A, phosphoERK, TPX2 and NEDD9 will be performed 
on pre-treatment biopsies on all cases. Non-Yale sites will submit FFPE to the Burtness Lab at 
Yale for analysis. 
Burtness Lab; 333 Cedar Street, NSB286, New Haven, CT 06510 
Post-treatment tumor biopsies will be obtained in Phase 1b (Expansion Phase) at the beginning of 
Cycle 3 and at disease progression. 
Organoid +/- PDX development will be conducted under the existing Yale Advanced Lung Cancer 
Tissue protocol (HIC #1603017333, Scott Gettinger, PI) under the direction of Dr. Katerina Politi. 
Material from pre- and post-treatment specimens from patients in the Phase 1b [Expansion Phase) 
who are treated at Yale will be approached to provide consent for these samples.  
 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
112 
November 11, 2022 
 
Amendment 2 
 
 
APPENDIX G. ETHICAL STANDARDS 
Ethics and Regulatory Considerations 
This study will be conducted according to Good Clinical Practice (GCP), US 21 Code of Federal 
Regulations (CFR) Part 50, (Protection of Human Subjects), US 21 CFR Part 56 (Institutional 
Review Boards), International Conference on Harmonisation Guidance for Industry, E6 Good 
Clinical Practice: Consolidated Guidance, the Nuremberg Code, and the Declaration of Helsinki. 
General Instructions 
The U.S. Food and Drug Administration (FDA) regulates studies of drugs, biologics, and medical 
devices. Consequently, these studies are subject to GCP and FDA regulations and guidance issued 
by the FDA and are included in, but not limited to, the following parts of the CFR and guideline 
document: 
• 21 CFR Part 11 – Electronic Records; electronic signatures 
• 21 CFR Part 50 – Protection of Human Subjects 
• 21 CFR Part 54 – Financial Disclosure 
• 21 CFR Part 56 – Institutional Review Boards 
• 21 CFR Part 312 – Investigational New Drug Application 
• FDA Guidance for Industry:  Oversight of Clinical Investigations – A Risk-Based 
Approach to Monitoring, August 2013 
• FDA Guidance for IRBs, Clinical Investigators, and Sponsors, June 2010 
• FDA Guidance for Industry: Investigator Responsibilities – Protecting the Rights, Safety, 
and Welfare of Study Subjects, October 2009 
• FDA Guidance for Industry and Investigators: Safety Reporting Requirements for INDs 
and BA/BE studies, December 2012 
• Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance, 1996 
Copies of these materials are available from the Sponsor upon request. The purpose of these 
regulations and legal obligations is to define the standards and principles for the proper conduct of 
clinical trials that have been developed by the medical, scientific, and regulatory communities. 
They are not intended to impede or restrict clinical research. 
The ethical standards defined within GCP are intended to ensure that: 
• Human subjects are provided with an adequate understanding of the possible risks of their 
participation in the study, and that they have a free choice to participate or not; 
• The study is conducted with diligence and in conformance with the protocol in such a way 
as to insure the integrity of the findings; 
• The potential benefits of the research justify the risks. 


Protocol No. VIC-1911-01 
 
VITRAC Therapeutics, LLC 
 
 
Confidential 
 
113 
November 11, 2022 
 
Amendment 2 
 
 
• VITRAC Therapeutics, LLC is the Sponsor of the IND. The Sponsor is responsible for the 
following: 
• Selecting qualified investigators, 
• Providing investigators with the information they need to properly conduct an 
investigation, 
• Ensuring proper monitoring of the investigation, 
• Ensuring that the study is conducted according to the general investigational plan and 
protocols contained in the IND, 
• Maintaining the IND, and 
• Ensuring that FDA and all participating investigators are properly informed of significant 
new information regarding adverse effects or risks associated with the drug being studied.