**Appendix 1:**

In the
\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--
teleconferences between the FDA and Corixa, the FDA identified issues
involving specific patients in their review of iodine I 131 tositumomab.
The following table summarizes the concerns identified by FDA's review
for confirmation of the long-term response in individual patients and
provides Corixa's responses to these concerns for each patient. The page
numbers reference the page of the patient's CRF file submitted as part
of Item 12 in the \-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--
partial response to the complete review letter.

+-----------+---------------+----------------------------------------+---+
| 00        | Question of   | Early versions of the MIRROR panel     |   |
| 4-013-008 | progression   | charter defined measurable disease as  |   |
|           | at study day  | any lesion ≥ 2 x 2 cm. This came to be |   |
|           | 425 based on  | interpreted operationally as any       |   |
|           | new lesion    | lesion with product of perpendicular   |   |
|           | with          | diameters (PPD) ≥ 4.0 cm^2^. MIRROR2   |   |
|           | dimensions    | and later charters have explicitly     |   |
|           | 2.2 x 1.8 cm  | used PPD measurements. In every        |   |
|           | (3.96 cm^2^)  | review, some lower limit must be set   |   |
|           |               | for measurable disease since normal    |   |
|           |               | lymph nodes have mass and normal lymph |   |
|           |               | nodes fluctuate in size in association |   |
|           |               | with immunoinflammatory reactions. In  |   |
|           |               | this case, the rule facilitated a      |   |
|           |               | correct description of the patient's   |   |
|           |               | course, because, without further       |   |
|           |               | treatment for lymphoma the pelvic      |   |
|           |               | lymph node in question becomes smaller |   |
|           |               | and the patient remains in clinical    |   |
|           |               | complete response almost 1000 days     |   |
|           |               | afterward.                             |   |
|           |               |                                        |   |
|           |               | Corixa believes that this patient      |   |
|           |               | should be included in the durable      |   |
|           |               | responders population.                 |   |
+-----------+---------------+----------------------------------------+---+
| 00        | Patient       | Patient received fludarabine from 03   |   |
| 4-014-001 | appears to be | June through 02 August 1996. CT scans  |   |
|           | responding to | prior to fludarabine were read by      |   |
|           | prior         | MIRROR panel as having an SPPD of      |   |
|           | chemotherapy  | 66.66 cm². Scans after fludarabine on  |   |
|           | at time of    | 21 Aug 1996 were read with an SPPD of  |   |
|           | study entry   | 43.16 cm². Baseline scans on study     |   |
|           |               | entry on \-\-- December 1996 were read |   |
|           |               | with an SPPD of 22.00 cm², a decrease  |   |
|           |               | of 67%. Thus the patient had a PR to   |   |
|           |               | fludarabine at study entry. The SPPD   |   |
|           |               | at week 7 was 9.24 cm².                |   |
|           |               |                                        |   |
|           |               | Corixa agrees that this patient is     |   |
|           |               | non-informative. In the primary        |   |
|           |               | efficacy analysis for study RIT-II-004 |   |
|           |               | this patient is excluded, but included |   |
|           |               | in long-term durable responders.       |   |
|           |               | However, inclusion of the patient in   |   |
|           |               | analyses of secondary endpoints in the |   |
|           |               | study and in the durable responders    |   |
|           |               | population does not diminish the       |   |
|           |               | fundamental findings. For the purposes |   |
|           |               | of labeling, Corixa will correct all   |   |
|           |               | analyses to reflect exclusion of this  |   |
|           |               | patient                                |   |
+-----------+---------------+----------------------------------------+---+
| 00        | Question of   | Patient had documented axillary        |   |
| 4-016-001 | progression   | adenopathy on physical exam at         |   |
|           | 9/25/97.      | baseline. The oncologist had called PD |   |
|           | Axillary node | based on a left axillary node, which   |   |
|           | noted on PE.  | was interpreted as new disease. Upon   |   |
|           | Oncology      | the radiologist's and oncologist's     |   |
|           | assessment PD | review, the left axillary node on      |   |
|           | later changed | 9/25/97 was noted to not have been a   |   |
|           | to PR.        | new lesion. Refer to CRF18A (page 137) |   |
|           |               | \-- all radiographs reviewed and       |   |
|           |               | radiologist concluded that the small   |   |
|           |               | axillary node was unchanged. Node      |   |
|           |               | measured 0.8 x 1.5 cm. After radiology |   |
|           |               | review, the Oncologist revised his     |   |
|           |               | assessment to PR and documented his    |   |
|           |               | reasoning on CRF 18C, page 196 of the  |   |
|           |               | case report forms, "palpable (L)       |   |
|           |               | axillary node also seen on old CT.     |   |
|           |               | Therefore, not progression."           |   |
|           |               |                                        |   |
|           |               | Corixa believes that this patient is   |   |
|           |               | correctly considered to be in PR on    |   |
|           |               | the date in question and not to have   |   |
|           |               | evidence of progressive disease.       |   |
+-----------+---------------+----------------------------------------+---+
| 00        | FDA           | CRF form dated 24 June 1999 (p 338)    |   |
| 4-016-001 | questioned    | denotes PD and states "patient also    |   |
|           | why the       | had bx of colonic polyp demonstrating  |   |
|           | investig      | a diffuse large cell lymphoma ". The   |   |
|           | ator-assessed | same CRF (p 339) is crossed out        |   |
|           | withdrawal    | without explanation and dated 25 July  |   |
|           | for PD on     | 2000 when patient records were         |   |
|           | \-\-- June    | obtained from the investigator which   |   |
|           | 1999 had been | stated: "During a routine screening    |   |
|           | lined out.    | colonoscopy, a lesion was found on the |   |
|           |               | ileocecal valve that was biopsied and  |   |
|           |               | came back with a diagnosis of B cell   |   |
|           |               | lymphoma. But a CT scan failed to      |   |
|           |               | demonstrate any evidence of disease.   |   |
|           |               | In addition, the pathology report from |   |
|           |               | the hemicolectomy revealed only        |   |
|           |               | lymphoid hyperplasia associated with   |   |
|           |               | the villous adenoma which was          |   |
|           |               | completely resection". The outpatient  |   |
|           |               | progress note stated: "the findings of |   |
|           |               | DLCL within the villous adenoma may    |   |
|           |               | have been artifactual secondary to     |   |
|           |               | evaluation of a small biopsy sample".  |   |
|           |               | Two issues were resolved. The patient  |   |
|           |               | did not have any 2x2 cm lesions on CT  |   |
|           |               | to justify the PD assessment and after |   |
|           |               | the partial colectomy, the pathology   |   |
|           |               | was read as lymphoid hyperplasia and   |   |
|           |               | not lymphoma. The patient was not      |   |
|           |               | withdrawn from study. The patient      |   |
|           |               | remains in CR as of 25 Oct 2001. We    |   |
|           |               | will attempt to obtain the pathology   |   |
|           |               | report from the biopsy and surgical    |   |
|           |               | resection. The monitor's trip report   |   |
|           |               | quoted above can be provided at your   |   |
|           |               | request.                               |   |
|           |               |                                        |   |
|           |               | Corixa believes that the patient's     |   |
|           |               | course has been appropriately          |   |
|           |               | described in the analyses provided.    |   |
+-----------+---------------+----------------------------------------+---+
| 00        | FDA           | On the date in question, July 1998,    |   |
| 4-014-008 | questioned    | the SPPD of all lesions decreased to   |   |
|           | whether the   | 37.44 from 37.6 at the previous        |   |
|           | patient had   | response visit. No new sites of        |   |
|           | PD in July    | disease were recognized. While the     |   |
|           | 1998 and not  | left axillary lesion became evaluable  |   |
|           | October 1998. | at 1.0 x 2.2 cm (2.2 cm2) from BDL x   |   |
|           |               | BDL at the previous response visit,    |   |
|           |               | this increase in isolation does not    |   |
|           |               | constitute progression as defined by   |   |
|           |               | the MIRROR Panel charter.              |   |
|           |               |                                        |   |
|           |               | Corixa believes that this patient's    |   |
|           |               | course has been accurately described   |   |
|           |               | in the analyses provided.              |   |
+-----------+---------------+----------------------------------------+---+
| 00        | FDA           | The original MIRROR Panel was based on |   |
| 4-016-003 | questioned    | indicator lesions, which for this      |   |
|           | why the PD at | patient were left (L) femur and right  |   |
|           | Week 19       | (R) femoral head. The patient was      |   |
|           | assessment    | classified as having PD on Week 19     |   |
|           | was changed   | based on the indicator lesions (p.     |   |
|           | to SD.        | 104). Upon discussion with the FDA,    |   |
|           |               | the MIRROR Panel charter was revised   |   |
|           |               | and an expanded review was conducted   |   |
|           |               | for all patients in study RIT-II-004.  |   |
|           |               | Per the new charter, all lesions were  |   |
|           |               | included in the lesion inventory. This |   |
|           |               | led to inclusion of one additional     |   |
|           |               | lesion (inguinal node) in the expanded |   |
|           |               | MIRROR Panel review. The response      |   |
|           |               | assessment was changed to SD (page     |   |
|           |               | 150: see documentation on CRF 18A) as  |   |
|           |               | the change in SPD of 22% did not meet  |   |
|           |               | the 25% increase in SPPD requirement   |   |
|           |               | for PD.                                |   |
|           |               |                                        |   |
|           |               | Corixa believes that this patient's    |   |
|           |               | course has been appropriately          |   |
|           |               | characterized in the analyses          |   |
|           |               | provided.                              |   |
+-----------+---------------+----------------------------------------+---+
| 002       | CRFs for Arm  | Corixa will provide bookmarked         |   |
| -030-925\ | B (prior to   | hypertext linked CRFs for patients     |   |
| 00        | crossover)    | 002-030-025 and 002-030-026.           |   |
| 2-030-926 | were          |                                        |   |
|           | requested by  |                                        |   |
|           | FDA.          |                                        |   |
+-----------+---------------+----------------------------------------+---+
| 00        | FDA suggested | Patient entered study with large (3 -- |   |
| 2-032-001 | that patient  | 4 cm) bilateral inguinal nodes. These  |   |
|           | had PD on 17  | decreased to the point that they were  |   |
|           | August 2000.  | not detected on 2 physical exams prior |   |
|           | The MIRROR    | to 17 Aug 2000.                        |   |
|           | Panel         |                                        |   |
|           | assessed the  | The physical examination note on 17    |   |
|           | patient as    | August 2000 (page 90) identifies left  |   |
|           | continuing in | inguinal adenopathy, which was         |   |
|           | CR on \--     | classified as stable (page 91). No     |   |
|           | August 2001.  | measurements were reported. The        |   |
|           |               | previous physical examination (page    |   |
|           |               | 88) did not report any inguinal        |   |
|           |               | adenopathy and the subsequent          |   |
|           |               | examination on 09 Nov 2000 (page 92)   |   |
|           |               | identifies 1 cm bilateral inguinal     |   |
|           |               | lymph nodes which were non-tender. The |   |
|           |               | next examination (page 94) on 15 Feb   |   |
|           |               | 2001 reported no palpable adenopathy.  |   |
|           |               |                                        |   |
|           |               | The MIRROR Panel tracked the two left  |   |
|           |               | inguinal nodes; these were reported as |   |
|           |               | \<1 x \<1 cm on the 14 August 2000     |   |
|           |               | radiographic evaluation. The MIRROR    |   |
|           |               | Panel radiologist and oncologist       |   |
|           |               | reported the patient to be in CR. The  |   |
|           |               | Investigator continued to follow       |   |
|           |               | patient as if in response.             |   |
|           |               |                                        |   |
|           |               | Corixa believes that this patient is   |   |
|           |               | correctly considered to be in CR on 14 |   |
|           |               | August 2000 and not to have evidence   |   |
|           |               | of progressive disease.                |   |
+-----------+---------------+----------------------------------------+---+
| 00        | FDA reviewer  | The medical notes (page 111) from 27   |   |
| 2-011-915 | identified a  | May 1997 reported a 1 cm right mid     |   |
|           | 1 cm cervical | posterior cervical node. Bilateral     |   |
|           | node in May   | cervical 1.5-2.0 cm nodes were noted   |   |
|           | 1997. The     | at Dec 1996 baseline (page 100). In    |   |
|           | MIRROR2 Panel | Jan 1997 1.5 cm cervical nodes were    |   |
|           | reported that | present. On 18 March 1997 the maximum  |   |
|           | the patient   | diameter of cervical and               |   |
|           | was in CR in  | supraclavicular nodes was 1.0 cm (page |   |
|           | April and     | 106). The 30 April 1997 medical notes  |   |
|           | July 1997 and | (page 109) reported a small 0.5 cm     |   |
|           | developed PD  | posterior cervical node. Subsequent    |   |
|           | on \-- March  | medical notes (page 113) reported      |   |
|           | 1998.         | cervical and supraclavicular nodes,    |   |
|           |               | measuring at most 0.5 cm. The          |   |
|           |               | referenced 27 May 1997 node does not   |   |
|           |               | appear to be a new node.               |   |
|           |               |                                        |   |
|           |               | The Investigator identified the right  |   |
|           |               | posterior cervical node at baseline    |   |
|           |               | (page 40) as 2.0 x 1.2 cm. On 15 July  |   |
|           |               | 1997 the lesion was 0.7 x 0.5 cm (page |   |
|           |               | 53). On 25 July 1999 (page 62) the     |   |
|           |               | lesion was no longer present.          |   |
|           |               |                                        |   |
|           |               | Both MIRROR and MIRROR2 Panels         |   |
|           |               | assessed the patient. Both reported    |   |
|           |               | that by radiographs the patient had    |   |
|           |               | all lesions BDL at the April and July  |   |
|           |               | assessments. Neither tracked the       |   |
|           |               | posterior cervical node.               |   |
|           |               |                                        |   |
|           |               | Corixa believes that this patient is   |   |
|           |               | correctly considered to be in CCR on   |   |
|           |               | the date in question and not to have   |   |
|           |               | evidence of progressive disease.       |   |
+-----------+---------------+----------------------------------------+---+
| 00        | FDA reviewer  | Open lung biopsy in April 1995 was     |   |
| 2-011-016 | was concerned | positive for follicular small cell     |   |
|           | that the      | lymphoma. After chemotherapy failed,   |   |
|           | patient had a | repeat bronchoscopy was positive for   |   |
|           | **complex     | lymphoma in 1996.                      |   |
|           | medical       |                                        |   |
|           | course:**     | At baseline, the Investigator noted    |   |
|           | confounding   | disease in lung and "midline abdominal |   |
|           | lung          | lesion anterior to the liver and       |   |
|           | involvement,  | superior to the kidney"; but stated    |   |
|           | abdominal     | only measurable disease is in right    |   |
|           | lesions       | base. MIRROR and MIRROR2 Panels (pages |   |
|           | associated    | 85 and 91) note disease in same areas, |   |
|           | with          | but state only measurable disease is   |   |
|           | infection and | in abdomen \[called mesenteric or      |   |
|           | surgery, and  | presplenic\]. MIRROR2 panel states on  |   |
|           | ovarian       | baseline CRF "disease in the lungs     |   |
|           | carcinoma     | probably sequelae". Investigator       |   |
|           | with          | Response: lung lesion decreases to 6.8 |   |
|           | associated    | cm^2^ at week 7 \[called a PR\].       |   |
|           | lesions and   | Lesion remains between 5.6 cm^2^ and   |   |
|           | surgical      | 7.1 cm^2^ for the next 10-11           |   |
|           | intervention. | measurements over 4 years and thus may |   |
|           |               | well have been scarring rather than    |   |
|           |               | active lymphoma.                       |   |
|           |               |                                        |   |
|           |               | The Investigator, MIRROR Panel, and    |   |
|           |               | MIRROR2 Panel all report that the      |   |
|           |               | patient never developed PD. All        |   |
|           |               | identified a baseline lesion and all   |   |
|           |               | noted tumor response and the absence   |   |
|           |               | of PD.                                 |   |
|           |               |                                        |   |
|           |               | On study day 80 the patient was        |   |
|           |               | admitted for acute abdominal pain      |   |
|           |               | secondary to ascending cholangitis.    |   |
|           |               | Cholecystectomy was performed with     |   |
|           |               | full resolution of problem.            |   |
|           |               |                                        |   |
|           |               | On \-- May 2001 the patient had a      |   |
|           |               | hemicolectomy and partial omentectomy  |   |
|           |               | that identified poorly differentiated  |   |
|           |               | adenocarcinoma, most compatible with   |   |
|           |               | Stage III ovarian carcinoma. The       |   |
|           |               | patient was withdrawn from study for   |   |
|           |               | treatment of the ovarian carcinoma     |   |
|           |               | with chemotherapy.                     |   |
|           |               |                                        |   |
|           |               | Corixa believes that the patient's     |   |
|           |               | lymphoma course has been appropriately |   |
|           |               | documented by the Investigator, MIRROR |   |
|           |               | Panel and MIRROR2 Panel, despite the   |   |
|           |               | complexity of the patient's medical    |   |
|           |               | history and co-morbidities.            |   |
+-----------+---------------+----------------------------------------+---+
| 00        | FDA reviewer  | This patient was described in an email |   |
| 2-011-009 | reported that | to George Mills on 19 September 2002   |   |
|           | the patient   | as follows:                            |   |
|           | had small     |                                        |   |
|           | baseline      | The 47 year old patient with a history |   |
|           | disease, poor | of follicular, small cleaved cell      |   |
|           | quality of    | lymphoma presented in 1989 with stage  |   |
|           | scans, and    | III-A disease. He received 2 cycles of |   |
|           | didn't know   | CVP with excellent response and        |   |
|           | what to make  | treatment was discontinued. He         |   |
|           | of patient.   | recurred 5 years later with cervical   |   |
|           |               | adenopathy. A brief course of          |   |
|           |               | chlorambucil produced another          |   |
|           |               | remission. He again developed inguinal |   |
|           |               | and cervical lymphadenopathy 2 years   |   |
|           |               | later. Daily chlorambucil was given    |   |
|           |               | for 6 months. Approximately one year   |   |
|           |               | later he developed rapidly enlarging   |   |
|           |               | inguinal adenopathy. Biopsy            |   |
|           |               | demonstrated histological              |   |
|           |               | transformation to follicular, large    |   |
|           |               | cell lymphoma. He presented to         |   |
|           |               | \-\-\-\-\-\-\-\-\-\-- Medical Center   |   |
|           |               | with a single abnormality on physical  |   |
|           |               | exam -- a submandibular mass that      |   |
|           |               | measured 2.5 x 2.0 cm by physical      |   |
|           |               | exam. An FNA was performed prior to    |   |
|           |               | study entry. Aspirated material was    |   |
|           |               | consistent with low grade lymphoma     |   |
|           |               | (small cleaved cell type). MIRROR2     |   |
|           |               | review noted two evaluable lesions on  |   |
|           |               | baseline CAT scan, a (R) jugular node  |   |
|           |               | with product of perpendicular          |   |
|           |               | diameters of 1.12 cm^2^ and a (R)      |   |
|           |               | infraparotid (submandibular) node of   |   |
|           |               | 3.52 cm^2^. Both lesions promptly      |   |
|           |               | became BDL x BDL following treatment   |   |
|           |               | with Bexxar. The patient was without   |   |
|           |               | evidence of progression at 371+ days.  |   |
|           |               | Assessments at year two were           |   |
|           |               | considered not assessable.             |   |
|           |               |                                        |   |
|           |               | Pathologically proven baseline disease |   |
|           |               | was observed to regress after iodine I |   |
|           |               | 131 tositumomab therapy. Corixa        |   |
|           |               | believes that the patient's course has |   |
|           |               | been appropriately documented by the   |   |
|           |               | Investigator, MIRROR Panel and MIRROR2 |   |
|           |               | Panel.                                 |   |
+-----------+---------------+----------------------------------------+---+
| 00        | FDA reviewer  | The patient was randomized to Arm B    |   |
| 2-034-906 | reported that | and developed Investigator-assessed PD |   |
|           | he did not    | and MIRROR Panel-assessed PD on \-\--  |   |
|           | have adequate | Dec 1998 (see MIRROR Panel listing for |   |
|           | pre-treatment | study RIT-II-002 study report \[BLA    |   |
|           | measures to   | submission                             |   |
|           | assess        | \-\-\-\-\-\-\-\-\-\-\-\-\-\--\] and    |   |
|           | patient.      | CRF for Week 7 submitted as part of    |   |
|           |               | the original BLA). The                 |   |
|           |               | Investigator-assessed PD at Week 7 was |   |
|           |               | based on a new lesion \>2 x 2 cm.      |   |
|           |               |                                        |   |
|           |               | The crossover baseline examination was |   |
|           |               | obtained one month later and           |   |
|           |               | identifies extensive disease prior to  |   |
|           |               | treatment on the \-\-\-- January 1999  |   |
|           |               | assessment (page 49). The MIRROR Panel |   |
|           |               | radiologist reported eleven lesions.   |   |
|           |               | At the \-- May 1999 (Month 3)          |   |
|           |               | evaluation, all lesions were BDL and   |   |
|           |               | continued to be reported as BDL        |   |
|           |               | through the last evaluation on 24 Nov  |   |
|           |               | 2000.                                  |   |
|           |               |                                        |   |
|           |               | Corixa believes that the patient's     |   |
|           |               | course has been appropriately          |   |
|           |               | documented by the MIRROR Panel and     |   |
|           |               | other submitted CRFs and lesion        |   |
|           |               | listings. This case was the subject of |   |
|           |               | a conversation between Corixa (Stewart |   |
|           |               | Kroll) and the Agency on               |   |
|           |               | \-\-\-\-\-\-\-\-\-\-\-\--. It was      |   |
|           |               | agreed that the Arm B pretreatment     |   |
|           |               | measurements were adequate for the     |   |
|           |               | assessment of the patient.             |   |
+-----------+---------------+----------------------------------------+---+
| 01        | FDA reviewer  | The MIRROR Panel identified 13         |   |
| 2-035-006 | suggested     | baseline lesions including a 3.8 x 2.8 |   |
|           | that the      | cm right neck lesion on the \-- Jan    |   |
|           | patient had   | 1999 baseline assessment (page 46). At |   |
|           | PD on \-\--   | the following assessment the right     |   |
|           | August 1999.  | neck lesion was 1.0 x 1.2 cm. No neck  |   |
|           |               | CT was available for \-\-- May 1999    |   |
|           |               | and at the \-\-- August 1999           |   |
|           |               | assessment, the right neck lesion was  |   |
|           |               | reported as 1.0 x 2.5 (\< 4 cm^2^).    |   |
|           |               | The MIRROR Panel reported the patient  |   |
|           |               | as a PR At the next evaluation on      |   |
|           |               | \-\-- Feb 2000 the neck lesion was 2.7 |   |
|           |               | x 1.8 cm and the MIRROR Panel reported |   |
|           |               | PD. At future MIRROR Panel evaluations |   |
|           |               | the neck lesion waxed and waned. The   |   |
|           |               | Investigator reports the patient to    |   |
|           |               | continue in CR as of \-- August 2001.  |   |
|           |               |                                        |   |
|           |               | Corixa believes that this patient's    |   |
|           |               | course has been accurately described   |   |
|           |               | by the MIRROR Panel with PD on 15 Feb  |   |
|           |               | 2000.                                  |   |
+-----------+---------------+----------------------------------------+---+
| 01        | FDA reviewer  | The MIRROR Panel identified 3 baseline |   |
| 2-037-001 | suggested     | lesions including a 1.7 x 1.5 cm right |   |
|           | that the      | lower lobe lesion on the 22 June 1998  |   |
|           | patient had   | baseline assessment (page 55). At the  |   |
|           | PD on 22 June | following assessments the right lower  |   |
|           | 2000.         | lobe lesion was 1.5 x 2.3 cm, 2.5 x    |   |
|           |               | 2.0, 2.2 x 1.7, 2.0 x 1.5, 2.5 x 2.0   |   |
|           |               | (22 June 2000), and then BDL x BDL for |   |
|           |               | all subsequent assessments. Under the  |   |
|           |               | MIRROR panel charter in effect, the    |   |
|           |               | oncologist had access to the lesion    |   |
|           |               | measurements. Employing clinical       |   |
|           |               | judgement, he documented in a joint    |   |
|           |               | response assessment for 22 June 2000   |   |
|           |               | that his assessment should be changed  |   |
|           |               | to CCR. He commented "please note that |   |
|           |               | the RLL lesion is unchanged within     |   |
|           |               | error of radiographic measurement"     |   |
|           |               | (page 111).                            |   |
|           |               |                                        |   |
|           |               | PD was documented by both the          |   |
|           |               | Investigator and MIRROR Panel in May   |   |
|           |               | 2001, based on the appearance of a new |   |
|           |               | preauricular lymph node.               |   |
|           |               |                                        |   |
|           |               | Corixa believes that this patient's    |   |
|           |               | course has been accurately described   |   |
|           |               | by the MIRROR Panel.                   |   |
+-----------+---------------+----------------------------------------+---+
| 01        | FDA reviewer  | A 0.5 cm palpable lymph node was       |   |
| 2-036-007 | suggested     | identified on the 23 May 2000 PE. On   |   |
|           | that the      | 13 June 2000 and 30 June 2000 the      |   |
|           | patient had   | lesion was reported as 1 cm. The       |   |
|           | PD on 23 May  | MIRROR Panel reported the patient to   |   |
|           | 2000.         | have PD on 26 June 2000.               |   |
|           |               |                                        |   |
|           |               | As the 0.5 cm lesion does not          |   |
|           |               | represent PD based on the MIRROR Panel |   |
|           |               | response definitions (≥ 4.0 cm2        |   |
|           |               | radiographically, or ≥ 1 cm by         |   |
|           |               | physical examination), Corixa believes |   |
|           |               | that this patient's course has been    |   |
|           |               | accurately described by the MIRROR     |   |
|           |               | Panel with PD on 26 June 2000.         |   |
+-----------+---------------+----------------------------------------+---+
| 00        | FDA reviewer  | Both the MIRROR Panel and MIRROR2      |   |
| 0-002-006 | suggested     | Panel assessed the patient to respond  |   |
|           | that the      | to therapy and have PD on 27 August    |   |
|           | patient had   | 1993.                                  |   |
|           | significant   |                                        |   |
|           | response      | Numerous patients have been reported   |   |
|           | prior to the  | to have tumor response subsequent to   |   |
|           | therapeutic   | the dosimetric dose and prior to the   |   |
|           | dose and      | therapeutic dose. In fact, the         |   |
|           | questioned if | observation that some patients         |   |
|           | the patient   | experience tumor regression prior to   |   |
|           | should be     | the therapeutic dose, when a 475 mg    |   |
|           | included as a | predose of unlabeled antibody          |   |
|           | durable       | preceeded the dosimetric dose, was one |   |
|           | responder.    | of the reasons for the selection of    |   |
|           |               | the 485 mg tositumomab dose as a       |   |
|           |               | standard part of the dosing scheme for |   |
|           |               | iodine I 131 tositumomab. (see the     |   |
|           |               | Rationale for Treatment Regimen in the |   |
|           |               | Clinical Pharmacology section of the   |   |
|           |               | original BLA; Section 8.3.6.3.1 (page  |   |
|           |               | 57)). Durable responders with multiple |   |
|           |               | dosimetric doses are summarized in     |   |
|           |               | Table 2. While multiple dosimetric     |   |
|           |               | doses were administered to some        |   |
|           |               | patients, no patient received more     |   |
|           |               | than a single predose at the highest   |   |
|           |               | level.                                 |   |
|           |               |                                        |   |
|           |               | Corixa believes that this patient's    |   |
|           |               | course is informative, and is          |   |
|           |               | accurately described by the results    |   |
|           |               | provided by the MIRROR panel.          |   |
+-----------+---------------+----------------------------------------+---+
| 00        | FDA reviewer  | Jan 1989 node biopsy demonstrated      |   |
| 0-002-056 | commented     | follicular small cell lymphoma. Second |   |
|           | that the      | biopsy in Dec 1990 demonstrated        |   |
|           | concomitant   | follicular large cell. Treatment with  |   |
|           | Breast CA     | 5 different chemotherapy regimens was  |   |
|           | made the case | delivered over the next 5 years.       |   |
|           | confusing.    | During evaluation for recurrence in    |   |
|           |               | May 1994, mammogram showed small       |   |
|           |               | lesion right breast. Lumpectomy        |   |
|           |               | demonstrated infiltrative ductal       |   |
|           |               | carcinoma. In July 1994 the patient    |   |
|           |               | received more chemotherapy for         |   |
|           |               | lymphoma, plus 4000 cGy RT to thoracic |   |
|           |               | spine, mediastinum and upper abdomen   |   |
|           |               | but not breast/axillary nodes. In      |   |
|           |               | March 1995 the patient had relapse in  |   |
|           |               | neck nodes. Biopsy confirmed large     |   |
|           |               | cell lymphoma and an abdomen CT was    |   |
|           |               | positive. In Sept 1995 the patient had |   |
|           |               | a recurrence of breast cancer in right |   |
|           |               | breast and underwent modified radical  |   |
|           |               | mastectomy on 31 Oct 1995 (a 2.5 cm    |   |
|           |               | lesion, with 4/11 nodes positive with  |   |
|           |               | extranodal extension). The patient     |   |
|           |               | entered study RIT-I-000 on 04 Dec      |   |
|           |               | 1995. Note that the protocol did not   |   |
|           |               | exclude patients who had a prior       |   |
|           |               | malignancy.                            |   |
|           |               |                                        |   |
|           |               | MIRROR 1 and 2 panel response          |   |
|           |               | assessments: followed baseline lesions |   |
|           |               | in axillae, aortocaval, and retrocaval |   |
|           |               | areas. In both response evaluations,   |   |
|           |               | disease quickly became BDL x BDL and   |   |
|           |               | then 0x0 until a mesentery recurrence  |   |
|           |               | in mesentery in Jan 1998 (page 77). In |   |
|           |               | MIRROR 2 a new pulmonary lesion in     |   |
|           |               | right apex measuring 6.4 cm^2^was      |   |
|           |               | noted at week 13 evaluation.           |   |
|           |               | Radiologist stated "In my opinion lung |   |
|           |               | lesion is much more likely from breast |   |
|           |               | cancer or a secondary lesion from      |   |
|           |               | therapy". At the 6 mo visit the same   |   |
|           |               | lesion measured 1.65 cm and at the one |   |
|           |               | yr BDL x BDL. At 9 months radiologists |   |
|           |               | notes "lesion at apex is probably scar |   |
|           |               | from therapy. In my opinion the        |   |
|           |               | patient is still a PR".                |   |
|           |               |                                        |   |
|           |               | Corixa agrees that the confounding     |   |
|           |               | effects of metastatic breast cancer in |   |
|           |               | this patient make assessment of        |   |
|           |               | lymphoma response problematic. Corixa  |   |
|           |               | will remove this patient from the      |   |
|           |               | durable responder population.          |   |
+-----------+---------------+----------------------------------------+---+