A Phase 1 Study to Assess Safety and Tolerability of Tremelimumab and Durvalumab, Administered With High Dose Chemotherapy and Autologous Stem Cell Transplant (HDT/ASCT)
Phase: PHASE1
Conditions: Multiple Myeloma
Sponsor: Ludwig Institute for Cancer Research

LUD2014-010 (NCT02716805). A Phase 1 Study to Assess Safety and Tolerability of Tremelimumab and 
Durvalumab, Administered with High Dose Chemotherapy and Autologous Stem Cell Transplant (HDT/ASCT) 
Expanded Access Protocol for LUD2014-010 Cohort 1 Subjects Continuing Tremelimumab Treatment  
12September2017 
Page 1 of 7 
 
LUD2014-010 was initiated under IND 129021 for durvalumab. 
Six subjects have been enrolled into Cohort 1. One subject (050-001-YEY) has discontinued therapy due 
to disease progression as discussed below.  Five subjects remain on study. The dosing scheme for Cohort 
1 is provided below. 
 
A partial clinical hold on this study issued by FDA on September 1, 2017. LICR has implemented this 
partial clinical hold with the following immediate actions: 
• 
The Principal Investigators at the two participating sites have been notified and they have 
informed their IRBs. 
• 
No new patients will be entered into this study. 
• 
Durvalumab will be discontinued in Subject 017-001-TLD, and durvalumab will not be started in 
any other patient.  
• 
A decision to amend or discontinue this protocol will be made at a later date. 
• 
All subjects will be informed of the results of the pembrolizumab clinical studies in Multiple 
Myeloma, the FDA partial clinical hold and, if applicable, reconsented prior to additional study 
treatment. 
• 
Ongoing subjects receiving clinical benefit may remain on study treatment with tremelimumab. 
In discussions with the two Principal Investigators as well as the study chair for this study, it was their 
desire and recommendation that the 4 ongoing subjects who are now in the transplant phase of the 
study be permitted to continue the tremelimumab treatment portion of the study after being informed 
of the data from the two pembrolizumab studies in Multiple Myeloma and re-consented. These subjects 
will be treated in accordance with this expanded access protocol as outlined in the flowchart provided in 
Figure 1.  
This addendum references version 3 of the LUD2014-010 protocol, the most recent version submitted to 
IND 129021 and approved by the IRBs. This protocol will be followed, superseded by the updated 
information in this expanded access protocol including the schedule of events, as the LUD2014-010 
protocol has information that would be referenced, such as preparation and administration of 
tremelimumab,  AE reporting, toxicity management, and other important guidance. 

LUD2014-010 (NCT02716805). A Phase 1 Study to Assess Safety and Tolerability of Tremelimumab and 
Durvalumab, Administered with High Dose Chemotherapy and Autologous Stem Cell Transplant (HDT/ASCT) 
Expanded Access Protocol for LUD2014-010 Cohort 1 Subjects Continuing Tremelimumab Treatment  
12September2017 
Page 2 of 7 
 
In Table 1 on the following page, detailed information on the 4 subjects including their disease stage 
and prior therapies as well as the dates on the next protocol-scheduled treatment is provided.  
These four subjects have received tremelimumab pre-transplant and 3 of them have also received the 
tremelimumab together with the lymphocyte re-infusions on day 3 post-transplant. Based on 
discussions with the Principal Investigators at the two study sites as well as the study chair, it is believed 
that these subjects are obtaining clinical benefit from this treatment and therefore would like to 
continue treatment with tremelimumab up to and including the day 100 and day 100 + 4 weeks dosing 
and followed as per Figure 1. No durvalumab will be administered in cycles 3-8. These subjects may 
receive lenalidomide maintenance after Cycle 3 at the investigator’s discretion.

LUD2014-010 (NCT02716805). A Phase 1 Study to Assess Safety and Tolerability of Tremelimumab and Durvalumab, Administered with High Dose 
Chemotherapy and Autologous Stem Cell Transplant (HDT/ASCT) 
Expanded Access Protocol for LUD2014-010 Cohort 1 Subjects Continuing Tremelimumab Treatment  
12September2017 
Page 3 of 7 
 
 
Table 1: LUD2014-010 Subjects Continuing Tremelimumab Therapy 
 
Subject 
Age/Gender 
Site 
Date of 
Enrollment 
Tremelimumab 75 mg 
Administration 
Next steps 
 
 
017-002-OWU 
64/male 
MSKCC 
22-Aug-17 
1 dose 
Pre ASCT Day -31 
3 doses tremelimumab Day 3, day 100 
and day 128 
Next dose tremelimumab 9/28/2017 
 
Background/reason 
for continuing 
treatment 
Initially diagnosed with ISS I, IgA kappa MM in January 2012 after presenting with neck/back pain secondary to a C3 
plasmacytoma, s/p corpectomy, laminectomy with fixation from C3-C5, then RT, induction therapy with Velcade, 
thalidomide, and dexamethasone, and ASCT with melphalan, with overall VGPR. In June 2016, relapsed with new bone 
lesions and treated with ixazomib, Revlimid, and dexamethasone with PR. In December 2016, progression of disease 
(POD) and switched to carfilzomib, pomalidomide, and dexamethasone, achieving a VGPR. In May 2017, POD with rising 
serum markers, rib/back pain, multiple FDG-avid plasmacytomas, and high-risk cytogenetics. Received VD-PACE x2 (May 
and June 2017) with excellent response (near resolution of FDG-avid plasmacytomas) and enrolled on the study.  The 
patient has aggressive, multiply relapsed disease that is still chemosensitive, proving rationale for salvage ASCT with 
melphalan. However, due to the nature of his disease, he is at extremely high risk for early relapse after transplant. The 
addition of an immune modulatory agent, like tremelimumab, offers the potential to improve his response to salvage 
ASCT, beyond the limited benefits of available standard treatments. The patient is extremely motivated to participate 
and specifically requested this study during his initial transplant consultation at our center.  
 

LUD2014-010 (NCT02716805). A Phase 1 Study to Assess Safety and Tolerability of Tremelimumab and Durvalumab, Administered with High Dose 
Chemotherapy and Autologous Stem Cell Transplant (HDT/ASCT) 
Expanded Access Protocol for LUD2014-010 Cohort 1 Subjects Continuing Tremelimumab Treatment  
12September2017 
Page 4 of 7 
 
Subject 
Age/Gender 
Site 
Date of 
Enrollment 
Tremelimumab 75 mg 
Administration 
Next steps 
 
 
050-002-TRA 
55/female 
Mount Sinai 
4-May-17 
2 doses 
Pre ASCT Day -31 
PBL Day 3 
2 doses tremelimumab days 100 and 128. 
Next dose tremelimumab 10/20/2017 
 
Background/reason 
for continuing 
treatment 
Primary Dx: IgG Lambda MM diagnosed in 2011. BMBx with monotypic plasma cells,85% overall cellularity. Normal 
Karyotype 46, XX. Fish : gain of IGH and TP53 and trisomy 13 associated with intermediate prognosis in multiple 
myeloma  
1. 
First line tx- VRD x3 Melphalan with ASCT and maintenance Revlimid 15 mg. Rev reduced to 10 mg and then 5 
mg due to cytopenias. Then off treatment until first relapse.  
2. 
Second line treatment- Ludwig protocol LUD2014-010 
Reason for continuing treatment-:  Patient has responded very well to transplant with intermediate risk genetics. FLC 
have dropped from 201.75 to 9.28 and M-Spike has dropped from 0.94 to 0.00 on 60 days post-transplant without any 
SAE 
050-003-NUL 
59/male 
Mount Sinai 
7-Jun-17 
2 doses 
Pre ASCT Day -31 
PBL Day 3 
2 doses tremelimumab days 100 and 128. 
Next Dose tremelimumab 9/21/2017 
 
Background/reason 
for continuing 
treatment 
IgM Kappa MM, initially diagnosed ISS stage 1, DS stage II. Presented w/ T2 plasmacytoma. BMBx 5/16/16 with 5% PCs. 
FISH +TP53 deletion, monosomy 12 and gain 1q25. 
First Line- induction KRDx4/with Ludwig protocol LUD2014-010.  
Reason for continuing treatment:  Patient has high-risk genetics that have possible early relapse with relatively chemo 
resistance clone could have better clinical benefit with the addition of immunomodulatory agents and transplant.  
Patient has 0.00 m-spike 30 days post-transplant and did not have any SAE during infusion. 

LUD2014-010 (NCT02716805). A Phase 1 Study to Assess Safety and Tolerability of Tremelimumab and Durvalumab, Administered with High Dose 
Chemotherapy and Autologous Stem Cell Transplant (HDT/ASCT) 
Expanded Access Protocol for LUD2014-010 Cohort 1 Subjects Continuing Tremelimumab Treatment  
12September2017 
Page 5 of 7 
 
Subject 
Age/Gender 
Site 
Date of 
Enrollment 
Tremelimumab 75 mg 
Administration 
Next steps 
 
 
050-004-OLY 
62/female 
Mount Sinai 
27-Jun-17 
2 doses 
Pre ASCT Day -31 
PBL Day 3 
2 doses tremelimumab days 100 and 128. 
Next dose tremelimumab 11/13/2017 
 
Background/reason 
for continuing 
treatment 
Smoldering multiple myeloma IgA Lambda, diagnosed in July 9, 2013. Progressive increase in paraprotein without CRAB 
symptoms. Bone marrow on December 20, 2013. ISS stage I; Durie-Salmon stage IA.  The result is abnormal and indicates 
a plasma cell clone with a 1q duplication, monosomy 13, and FGFR3/IGH fusion, t(4;14). At diagnosis, t(4;14) and 1q 
duplication are associated with an intermediate prognosis in multiple myeloma   
1. First Line Therapy January 13, 2014: VRD x 5 cycles; CR 04/01/14. R25/D20 beginning 07/16/2014 for 6 cycles. 
R10/D4 maintenance. 
2. Biochemical Relapse March 2017. Ludwig Protocol LUD2014-010 
Reason for continuing treatment:  Patient has responded very well to transplant with greater than low risk genetics. M-
spike prior to transplant was 0.63 which has dropped to 0.0 after 30 days post-transplant. Patient has not had any SAE 
with infusion treatments. 
 

LUD2014-010 (NCT02716805). A Phase 1 Study to Assess Safety and Tolerability of Tremelimumab and 
Durvalumab, Administered with High Dose Chemotherapy and Autologous Stem Cell Transplant (HDT/ASCT) 
Expanded Access Protocol for LUD2014-010 Cohort 1 Subjects Continuing Tremelimumab Treatment  
12September2017 
Page 6 of 7 
 
Figure 1: Schedule of Procedures 
 
Study Flowchart for Cohort 1 
Screenin
g / 
Baseline 
Treatment  
Pre ASCT 
HDT 
/ASCT 
PBL 
Post ASCT and PBL  
Cycle 1 
Cycle 2 
Treatment  weeks (based on 
ASCT) 
-9 to -5 
  
1 
2 
5 
9 
14 
18 
Cycle Day 
  
1 
1 
Treatment days (based on 
ASCT) 
-62 to -34 
-
33±2 
-31±2 
-10 to -3 
-2 
0 
3  
12 
±4 
30 +10 
60±4 
100±10 
128±4 
Study Drugs and PBL Administration 
Tremelimumab (75 mg) 
  
  
X 
  
  
  
X2 
  
  
  
X 
X 
 Melphalan  
  
  
  
  
x 
  
  
  
  
  
  
  
Autologous Stem cell transplant 
(ASCT) 
  
  
  
  
  
x 
  
  
  
  
  
  
Peripheral blood lymphocyte 
(PBL) pheresis  
  
  
  
x 
  
  
  
  
  
  
  
  
PBL infusion 
  
  
  
  
  
  
X2 
  
  
  
  
  
Prevnar - 13 
  
X1 
  
  
  
  
  
  
x1 
x1 
  
  
Multiple Myeloma Tests 
PET/CT scan or MRI spine As 
clinically 
X 
  
  
  
  
  
  
  
  
  
x 
  
Myeloma serum tests5 
X 
  
  
x 
  
  
  
  
  
  
x 
x 
Myeloma urine tests5 
X 
  
  
x 
  
  
  
  
  
  
x 
x 
Study Procedures and Examinations 
Physical Exam (incl. weight and 
vitals) 
X 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
12-Lead ECG 
X 
  
  
  
  
  
  
  
  
  
  
  
ECHO- Heart Ultrasound  
X 
  
  
  
  
  
  
  
  
  
  
  
Lung Function tests 
X 
  
  
  
  
  
  
  
  
  
  
  
Routine Laboratory Samples 
Routine blood Test (chemistry 
and complete blood count)3 
-40 to -33 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Endocrine panel (Thyroid tests)3 
-40 to -33 
  
  
  
x 
  
  
  
  
  
x 
  
Urinalysis3 
-40 to -33 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Serum pregnancy test (urine 
test only on Day -31)3 
-40 to -33 
  
x 
  
  
x 
x 
  
  
  
x 
x 
Bone Marrow Samples 
Bone Marrow Sampling (tissue 
and aspirate) for routine and 
research laboratories 
x 
  
  
  
  
  
  
  
  
  
x 
  
Whole Blood for Research Labs 
Whole Blood Sampling for 
Research testing 
X 
X3 
 X3 
X4 
X3 
  
  
X3 
X3 
X3 
X3 
X3 
1. Prevnar dose and tremelimumab dose must be separated by a minimum of 48 hrs. 
2. Tremelimumab must be infused within 24 hours following PBL infusion 
3. Collect pre-dose (prior to drug administration) or other infusion. Note: It is strongly recommended that hematology, 
chemistry and pregnancy test (when applicable) results are reviewed before dosing. 
4. Samples will be removed from the pheresis product 
5. If serum and urine IF are positive, subsequent analysis is not necessary unless the subject achieves a response of VGPR or greater 
6. For subjects who did not experience progression while on study 
 
 
 

LUD2014-010 (NCT02716805). A Phase 1 Study to Assess Safety and Tolerability of Tremelimumab and 
Durvalumab, Administered with High Dose Chemotherapy and Autologous Stem Cell Transplant (HDT/ASCT) 
Expanded Access Protocol for LUD2014-010 Cohort 1 Subjects Continuing Tremelimumab Treatment  
12September2017 
Page 7 of 7 
 
Study Flowchart for Cohort 1 continued 
On Study Follow-up 
Post Study Follow-up 
Every 6 months for up 
to 2 years from start of 
treatment 
 
Cycle 3  
Cycle 3 or  
Last study drug 
+28  ±4 days 
Cycle 3 or  
Last study drug 
+56 ±4 days 
Cycle 3 or  
Last study drug 
+91 ±4 days  
End of Study 
 
Treatment  weeks (based on ASCT) 
22 
Cycle Day 
1 
Treatment days (based on ASCT) 
156 ±4 
  
  
  
Multiple Myeloma Tests 
PET/CT scan or MRI spine As clinically 
  
x 
  
  
Myeloma serum tests5  
x 
x 
  
Myeloma urine tests5 
x 
x 
  
Study Procedures and Examinations 
Physical Exam (incl. weight and vitals) 
x 
x 
x 
x 
  
12-Lead ECG 
  
x 
  
  
  
ECHO- Heart Ultrasound  
  
  
  
  
  
Lung Function tests 
  
  
  
  
  
Routine Laboratory Samples 
Routine blood Test (chemistry and complete blood 
count) 
x 
x 
x 
x 
  
Endocrine panel (Thyroid tests) 
x 
x 
  
x 
  
Urinalysis 
x 
x 
x 
x 
  
Serum pregnancy test (urine test only on Day -31)3 
  
x 
  
x 
  
Bone Marrow Samples 
Bone Marrow Sampling (tissue and aspirate) for routine 
and research laboratories 
  
x 
  
  
  
Whole Blood for Research Labs 
Whole Blood Sampling for Research testing 
x 
x 
  
Long-Term Follow-up 
 
 
 
Overall Survival 
 
 
x 
Progression Free Survival6 
 
 
x 
1. Prevnar dose and tremelimumab dose must be separated by a minimum of 48 hrs. 
2. Tremelimumab must be infused within 24 hours following PBL infusion 
3. Collect pre-dose (prior to drug administration) or other infusion. Note: It is strongly recommended that hematology, 
chemistry and pregnancy test (when applicable) results are reviewed before dosing. 
4. Samples will be removed from the pheresis product 
5. If serum and urine IF are positive, subsequent analysis is not necessary unless the subject achieves a response of VGPR or greater 
6. For subjects who did not experience progression while on study