On June 3, 2023 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported that results from a Phase 1 dose-expansion study of luveltamab tazevibulin (luvelta), a novel Folate receptor alpha (FolRα)-targeting ADC, in patients with advanced ovarian cancer were featured in an oral presentation at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO 2023) Annual Meeting in Chicago, IL (Press release, Sutro Biopharma, JUN 3, 2023, View Source [SID1234632429]). In parallel, the Company continues to advance the clinical development of luvelta and announced that sites are now open for enrollment in REFRaME-O1, the pivotal Phase 2/3 study for patients with platinum-resistant ovarian cancer.

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Data from the Phase 1 dose-expansion study of luvelta were presented by co-Principal Investigator, Ana Oaknin, M.D., Ph.D., Head of the Gynecological Tumor Unit and Attending Physician at the Vall d’Hebron University Hospital in Barcelona and Principal Clinical Investigator of the Gynecological Malignancies Group at the Vall d’Hebron Institute of Oncology. Consistent with data reported in January 2023, luvelta demonstrated substantial clinical benefit in FolRα-selected patients, defined by Tumor Proportion Score (TPS) of >25%, irrespective of staining intensity, which represents approximately 80% of the advanced ovarian cancer patient population.

When focusing on patients with a FolRα expression level above 25% (Tumor Proportion Score, or TPS >25% and regardless of staining intensity), the efficacy outcomes exhibited a 37.5% ORR, a median DOR of 5.5 months, and a median PFS of 6.1 months. Notably, at the higher starting dose level of 5.2 mg/kg, these patients experienced even higher response rates, with a 43.8% ORR, a median DOR of 5.4 months, and a median PFS of 6.6 months. Responses were seen in FolRα expressing patients with TPS >25%, addressing patients who may not be eligible for other approved therapies targeting FolRα.

"I am encouraged by the preliminary efficacy, durability, and favorable safety profile observed in this study, which signify the potential of luveltamab tazevibulin as a promising therapeutic option for patients with ovarian cancer who are not well supported by current standard of care," commented Dr. Oaknin. "The population of ovarian cancer patients that may benefit from treatment with luveltamab tazevibulin represents a significant unmet medical need globally."

"We are excited to share these promising data in an oral presentation at ASCO (Free ASCO Whitepaper), a globally respected oncology conference, which demonstrate the meaningful clinical benefit that luvelta may offer to ovarian cancer patients across a broad range of heterogeneity in FolRα-expression," said Anne Borgman, M.D., Sutro’s Chief Medical Officer. "On the heels of these positive results, we are thrilled that REFRaME, our pivotal Phase 2/3 trial, is officially underway. From the clinical and nonclinical data gathered, we maintain our positive outlook that luvelta could potentially serve multiple additional indications where patients express FolRα."

About Luveltamab Tazevibulin
Luveltamab tazevibulin, abbreviated as "luvelta" and formerly known as STRO-002, is a FolRα-targeting antibody-drug conjugate (ADC) designed to treat a broad range of patients with ovarian cancer, including those with lower FolRα-expression who are not eligible for approved treatment options targeting FolRα. Developed and manufactured with Sutro’s cell-free XpressCF platform, luvelta is a homogeneous ADC with four hemiasterlin cytotoxins per antibody, precisely positioned to efficiently deliver to the tumor while ensuring systemic stability after dosing. Sutro recently initiated REFRaME, a Phase 2/3 registration-directed study for patients with platinum-resistant ovarian cancer. The company has ongoing trials in patients with endometrial cancer and in combination with bevacizumab in patients with ovarian cancer. The company is also assessing the clinical path forward for CBF/GLIS2 acute myeloid leukemia, a rare subtype of pediatric cancer, as well as non-small cell lung cancer.

On June 3, 2023 Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) reported updated results from an interim analysis of the ARC-7 study in patients with first-line, metastatic non-small cell lung cancer (NSCLC) with PD-L1 tumor proportion score (TPS) ≥50% without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations. ARC-7 is the first Phase 2, randomized, open-label study evaluating the combinations of Fc-silent anti-TIGIT monoclonal antibody domvanalimab plus anti-PD-1 monoclonal antibody zimberelimab (doublet) and domvanalimab plus zimberelimab and etrumadenant, an A2a/b adenosine receptor antagonist (triplet), versus zimberelimab monotherapy (Press release, Gilead Sciences, JUN 3, 2023, View Source [SID1234632428]). These results will be presented today during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series: Rapid Abstract Updates session by Melissa L. Johnson, M.D., Director, Lung Cancer Research, Sarah Cannon Research Institute, and Lead Investigator for the ARC-7 study.

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"Progression-free survival curves showed early separation of both domvanalimab-containing arms from the zimberelimab arm, which was consistently maintained, and supports the potential therapeutic benefit of inhibiting the TIGIT pathway," said Melissa L. Johnson, M.D., Director, Lung Cancer Research, Sarah Cannon Research Institute, and Lead Investigator for the ARC-7 study. "I was also encouraged by the consistency of meaningful improvements across other outcome measures for the domvanalimab-containing arms. I look forward to continuing to work with Gilead and Arcus on the dom-zim combinations."

At the time of data cutoff (DCO), February 7, 2023, safety and efficacy were evaluated in all patients randomized and treated (n=150). With a median follow-up time of approximately 18 months, both domvanalimab-containing study arms demonstrated sustained, clinically meaningful improvements in progression-free survival (PFS) compared to zimberelimab monotherapy, with a 33% reduction in risk of disease progression or death for the doublet and 28% for the triplet.

The efficacy data, including PFS and ORR, are summarized in the table below:

Endpoint

zimberelimab (Z)
monotherapy
(n=50)

domvanalimab +
zimberelimab
(DZ)
(n=50)

etrumadenant +
domvanalimab +
zimberelimab
(EDZ) (n=50)

Progression-Free Survival (PFS)

Median in Months (95% CI)

5.4 (2.7, 9.7)

9.3 (4.1, NE)

9.9 (4.8, 14.6)

Hazard Ratio* (95% CI)

0.67 (0.4, 1.13)

0.72 (0.63, 1.8)

Six-month PFS rate (95% CI)

45% (30, 59)

58% (43, 72)

62% (48, 76)

12-month PFS rate (95% CI)

25% (11, 40)

41% (26, 56)

44% (29, 59)

Objective Response Rate (ORR)

ORR+ Confirmed + Pending (95% CI)

15 (30%)

[17.9%, 44.6%]

20 (40%)++

[26.4%, 54.8%]

22 (44%)

[30%, 58.7%]

Complete Response

1 (2%)

1 (2%)

0 (0%)

Partial Response Confirmed

14 (28%)

18 (36%)

22 (44%)

Partial Response Pending

0 (0%)

1 (2%)

0 (0%)

Stable Disease

16 (32%)

18 (36%)

16 (32%)

Progressive Disease

12 (24%)

4 (8%)

7 (14%)

Not Evaluable (NE)

7 (14%)

8 (16%)

5 (10%)

CI=Confidence Interval
*

Comparing DZ and EDZ arms to Z monotherapy.

+

Per RECIST 1.1

++

Across all arms, one participant in the DZ arm had a response pending confirmation, which was confirmed after DCO date.

–

Preliminary duration of response (DoR) analyses favor domvanalimab-containing arms, with median DoR (range, ‘+’: censored) as follows: Z: 13.2mo (+1.4-+19.4), DZ: not reached (2.8-+26.6), EDZ: 23.7mo (2.6-23.7).

–

As of the DCO, approximately twice as many participants remain on study treatment in the domvanalimab-containing arms compared to zimberelimab monotherapy [Z: (n=9), DZ: (n=17), EDZ: (n=20)].

–

Consistent ORR and PFS improvements were shown for the domvanalimab-containing arms in a post-hoc analysis of centrally confirmed PD-L1-high patients.

"At this analysis, the domvanalimab-containing study arms continued to show improved efficacy across multiple measures and both the doublet and triplet arms were generally well tolerated," said Dimitry S.A. Nuyten, M.D., Ph.D., Chief Medical Officer of Arcus Biosciences. "These data reinforce our confidence in the domvanalimab program."

"The ARC-7 proof-of-concept study has critically advanced our understanding of the activity of domvanalimab, the first Fc-silent anti-TIGIT monoclonal antibody in pivotal trials," said Bill Grossman, M.D., Ph.D., Senior Vice President, Therapeutic Area Head, Gilead Oncology. "We look forward to quickly advancing our four ongoing Phase 3 registrational programs in NSCLC and upper GI cancers."

No unexpected safety signals were observed across the three study arms at the time of DCO. The domvanalimab-containing study arms appeared to be generally well tolerated and showed an overall safety profile consistent with the known safety profiles of each individual molecule to date. Incidence of infusion-related reactions was low across all treatment arms: 4%, 4% and 12% for zimberelimab monotherapy and the domvanalimab-doublet and -triplet arms, respectively. The addition of domvanalimab to zimberelimab did not increase the incidence of infusion-related reactions, consistent with the Fc-silent design of domvanalimab.

Domvanalimab, zimberelimab and etrumadenant are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use globally, and their safety and efficacy for the treatment of lung cancer have not been established.

About the ARC-7 Study

The ARC-7 study is the first Phase 2, multicenter, three-arm, randomized, open-label study evaluating the safety and efficacy of anti-TIGIT antibody domvanalimab plus anti-PD-1 antibody zimberelimab (doublet) versus domvanalimab plus zimberelimab and etrumadenant (triplet), an A2a/b adenosine receptor antagonist, versus zimberelimab monotherapy in 150 patients with first-line metastatic non-small cell lung cancer (NSCLC) with PD-L1 TPS ≥50% and no EGFR or ALK mutations. Patients are randomized 1:1:1 across the three study arms, and patients who progress on zimberelimab monotherapy may cross over to receive the triplet. At the time of this interim analysis, 150 patients had a median follow-up of 18.5 months. The co-primary endpoints are objective response rate and progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Secondary endpoints include duration of response, disease control rate, overall survival and safety. ARC-7 is a proof-of-concept study to assess the safety and efficacy of domvanalimab-containing study arms over zimberelimab monotherapy. More information about ARC-7 is available at: View Source

About Domvanalimab

Domvanalimab is the first Fc-silent investigational monoclonal antibody in pivotal trials that is designed to block and bind to the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), a protein receptor on immune cells that acts as a brake on the immune response. Cancer cells can exploit TIGIT to avoid detection by the immune system. By binding to TIGIT, domvanalimab is expected to free up immune activating pathways and activate immune cells to attack and kill cancer cells. Domvanalimab has demonstrated complete receptor coverage on all TIGIT-expressing peripheral leukocytes.

Domvanalimab is being evaluated in four registrational Phase 3 studies across lung and gastrointestinal cancers, including: (1) ARC-10, evaluating domvanalimab plus zimberelimab versus pembrolizumab in first-line locally advanced or metastatic PD-L1 ≥50% NSCLC; (2) PACIFIC-8, being operationalized by AstraZeneca, evaluating domvanalimab plus durvalumab in unresectable Stage 3 NSCLC; (3) STAR-121, evaluating domvanalimab plus zimberelimab and chemotherapy versus pembrolizumab plus chemotherapy in first-line PD-L1-unselected NSCLC; and (4) STAR-221, evaluating domvanalimab plus zimberelimab and chemotherapy versus nivolumab plus chemotherapy in first-line locally advanced, unresectable or metastatic gastric, esophageal and gastro-esophageal junction adenocarcinomas.

On June 3, 2023 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported positive clinical data from the Phase 1 study of the off-the-shelf (OTS) PRGN-2009 AdenoVerse immunotherapy alone and in combination with an investigational anti-PDL1/TGF-Beta Trap checkpoint inhibitor (bintrafusp alfa) in patients with recurrent/metastatic (R/M) HPV-associated cancers (clinical trial identifier: NCT04432597) at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract# 2628) (Press release, Precigen, JUN 3, 2023, View Source [SID1234632427]).

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"Recurrent/metastatic HPV-associated cancers such as cervical, anal, and oropharyngeal are incurable by current therapies and there remains significant unmet need for new safe and effective treatments. Checkpoint inhibitors alone have shown some promise, but have not produced durable responses and many patients relapse or become resistant," said Helen Sabzevari, PhD, President and CEO of Precigen. "In our Phase 1 study, combining PRGN-2009 with checkpoint inhibition demonstrated a favorable safety profile and resulted in a 30% ORR with prolonged duration of responses in patients with heavily pre-treated HPV-associated cancers, including those who were checkpoint blockade resistant. We are highly encouraged by these Phase 1 data and, as we announced on May 31, we are moving rapidly to initiate a Phase 2 study to combine PRGN-2009 with a checkpoint inhibitor to further investigate safety and efficacy in recurrent or metastatic cervical cancer. This new trial is the second Phase 2 for PRGN-2009 AdenoVerse, adding to the ongoing Phase 2 in oropharyngeal squamous cell carcinoma."

PRGN-2009 is an OTS investigational immunotherapy utilizing the AdenoVerse platform designed to activate the immune system to recognize and target HPV-positive (HPV+) solid tumors. PRGN-2009 is a novel, replication-incompetent gorilla adenovirus targeting HPV 16/18. PRGN-2009 can be administered repeatedly leading to enhancement of T-cells without increasing neutralizing antibodies. PRGN-2009 is under development through a Cooperative Research and Development Agreement, or CRADA, within the Center for Immuno-Oncology (CIO), Center for Cancer Research (CCR), National Cancer Institute (NCI), part of the National Institutes of Health (NIH).

The Phase 1 trial is an open label, single-center study evaluating safety and response of PRGN-2009 as a monotherapy (Arm A) and in combination with bintrafusp alfa (Arm B) in previously treated adult patients with R/M HPV-associated cancers. In the monotherapy arm, patients (N = 6) enrolled in two sequential PRGN-2009 dose level cohorts, Dose Level 1 (1×1011 particle units (PU)) and Dose Level 2 (5×1011 PU) delivered via subcutaneous injection. In the combination arm, PRGN-2009 was administered at the recommended phase 2 dose (RP2D) in combination with bintrafusp alfa.

The primary objective of the study was to evaluate safety and RP2D of PRGN-2009 and safety of PRGN-2009 in combination with a checkpoint inhibitor. Secondary objectives included Objective Response Rate (ORR) (per RECIST 1.1), and progression free survival (PFS).

Patient Characteristics
Seventeen adult patients were enrolled in the Phase 1 study (Table 1). Patients received up to 20 doses of PRGN-2009 for a duration of 1.8 to 17.9 months in the monotherapy arm and 0.5 to 23.0 months in the combination arm. The median age in both arms was 61. The median number of prior lines of therapies in the metastatic setting was 2.5 for the monotherapy arm and 2 for the combination arm. All patients in the monotherapy arm (N=6) and 10 of 11 patients in the combination arm received prior immune checkpoint blockade (ICB) therapy.

Table 1. Patient Demographics and Clinical Characteristics

Monotherapy Arm (N=6)

Combination Arm (N=11)

Age, years (median, range)

61 (43-70)

61 (54-80)

Female, n (%)

6 (100)

3 (27)

Tumor types (n,%)

Oropharyngeal

Cervical

Anal

Vaginal

–

3 (50.0)

2 (33.3)

1 (16.7)

7 (63.6)

3 (27.3)

1 (9.1)

–

HPV status (n, %)

HPV16

HPV18

Other

N/A

3 (50)

–

2 (33.3)

1 (16.7)

9 (81.8)

1 (9.1)

1 (9.1)

–

Previous lines of therapy in metastatic setting, median (range)

2.5 (2-3)

2 (1-4)

ICB exposure, n (%)

Primary resistance

Secondary resistance

6 (100)

4 (66.7)

2 (33.3)

10 (90.9)

5 (50)

5 (50)

Safety Data
PRGN-2009 treatment in both monotherapy and combination arms was safe and well-tolerated (Table 2). In both study arms, there was a low incidence of treatment-related adverse events (TRAEs) with only Grade 1 or 2 TRAEs in the monotherapy arm. The most common TRAEs in the monotherapy arm were injection site reactions, flu-like symptoms, fatigue and rash. In addition to these in the combination arm, patients also experienced Grade 1 or 2 epistaxis, headache, keratoacanthoma, fever, decreased lymphocyte count, anemia and oral hemorrhage. TRAEs reported in the combination arm were in line with the safety profile reported for bintrafusp alfa and only Grade 1 or 2 TRAEs were attributable to PRGN-2009 in the combination arm.

Table 2: Safety Data

Monotherapy Arm (N=6)

Combination Arm (N=11)

Treatment-related adverse events, n (%)

Grade 1-2

(all)

Grade 3-4

(all)

Grade 1-2

(≥10%)

Grade 3-4

(all)

Injection site reactions

4 (66.7)

0

9 (81.8)

0

Flu-like symptoms,

3 (50.0)

0

6 (54.5)

0

Fatigue

2 (33.3)

0

3 (27.3)

0

Rash, maculopapular

1 (16.7)

0

3 (27.3)

0

Epistaxis

0

0

3 (27.3) *

0

Headache

0

0

3 (27.3)

0

Keratoacanthoma

0

0

3 (27.3)*

0

Fever

0

0

2 (18.2)

0

Lymphocyte count, decreased

0

0

2 (18.2)*

0

Anemia

0

0

2 (18.2)*

0

Oral hemorrhage

0

0

2 (18.2)*

0

Duodenal Hemorrhage

0

0

0

2 (18.2)*†‡

Pharyngeal mucositis

0

0

0

1 (9.1) *

*Attributed to bintrafusp alfa; † both patients concurrently receiving NSAIDs; ‡ 1 patient died following refusal of standard supportive medical management measures (blood transfusion).

Clinical Activity
Tumor responses were observed in patients after treatment with PRGN-2009 in combination with bintrafusp alfa (Arm 1B), including in ICB-resistant patients (Table 3). PRGN-2009 combined with bintrafusp alfa resulted in a 30% ORR in patients with pretreated R/M HPV-associated cancers with prolonged duration of responses (Table 3, Figure 1). The majority of patients developed HPV-16 and/or HPV-18 specific immune responses after treatment with PRGN-2009 in both monotherapy and combination arms (Table 4) without the development of neutralizing antibodies (Figure 2).

Table 3: Best Response by Arm

Monotherapy Arm

Combination Arm

Evaluable patients, n

6

10

Best response, n

CR

–

1a

PR

–

2c,d

SD

4b

1

PD

2

6

ORR, % (95% CI)

–

30 (6.7-65.3)

a immune checkpoint blockade (ICB)-resistant; b 1 SD confirmed; c 1 PR confirmed; d 1 ICB-resistant, 1 TCR treatment-resistant; 2 patients treated beyond progression without delayed response; CI: confidence interval

Figure 1: Time to Response and Duration of Response to Treatment

Figure 1: Time to Response and Duration of Response to Treatment

Table 4: HPV-specific T-cell Immune Responses

Monotherapy Arm

Combination Arm

HPV-16, n/N (%)

5/6 (83)

7/10 (70)

HPV-18, n/N (%)

5/6 (83)

7/8 (88)

HPV-16 and/or HPV-18 n/N (%)

6/6 (100)

8/10 (80)

N: number of patients tested

Figure 2: Neutralizing Antibodies

Figure 2: Neutralizing Antibodies

Figure 2: Neutralizing Antibodies

Phase 2 Clinical Study in Newly Diagnosed Oropharyngeal Squamous Cell Carcinoma
The Phase 2 portion of the study is ongoing at the RP2D and enrollment was completed in the monotherapy arm with 20 evaluable patients with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC). An interim clinical data presentation from the Phase 2 monotherapy arm is expected in the second half of 2023.

Phase 2 Randomized Control Study in Recurrent or Metastatic Cervical Cancer
The Company recently announced that the US Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application to initiate a Phase 2 study of the first-in-class PRGN-2009 OTS AdenoVerse immunotherapy in combination with pembrolizumab in patients with recurrent or metastatic cervical cancer. The Phase 2 randomized, open-label, two-arm, multicenter study will evaluate the efficacy and safety of PRGN-2009 in combination with pembrolizumab versus pembrolizumab monotherapy in patients with recurrent or metastatic cervical cancer who are pembrolizumab resistant.

On June 3, 2023 Affimed N.V. (Nasdaq: AFMD) ("Affimed", or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported the presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting of safety and efficacy data from the EGFR mutant NSCLC expansion cohort of its ongoing phase 1/2 study investigating innate cell engager (ICE) AFM24 as monotherapy (Press release, Affimed, JUN 3, 2023, View Source [SID1234632426]). The data included 15 evaluable patients and showed encouraging early signs of clinical activity including confirmed partial responses and durable stable disease. EGFR mutant NSCLC is a very aggressive and resistant tumor type in which most classical NSCLC treatments achieve limited to no clinical activity, especially in more advanced patients. Affimed’s innate cell engager AFM24 aims to reactivate the innate and consequently the adaptive immune system to recognize and destroy EGFR mutant tumors.

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"The treatment options for patients with advanced solid tumors and EGFR alterations are limited by the development of resistance to existing EGFR targeting therapies and by modest activity of checkpoint inhibitors. The results we have seen with AFM24 monotherapy in an expansion cohort of advanced, refractory NSCLC patients with EGFR mutations indicate that activating the innate immune pathway in this patient population results in anti-tumor activity and may offer a novel therapeutic approach. Given the underlying molecular pathways, we believe that AFM24 could potentially enable checkpoint inhibitors to achieve a positive effect," said Dr. Anthony El-Khoueiry, Associate Director of Clinical Research at USC Norris Comprehensive Cancer Center and principal investigator of the AFM24 studies.

The AFM24 EGFR mutant NSCLC cohort is part of the AFM24-101 open-label, non-randomized, multi-center, phase 1/2a study (NCT04259450) investigating the safety, tolerability, and preliminary efficacy of AFM24 monotherapy in patients with advanced or metastatic EGFR+ solid tumors. Other cohorts being investigated included colorectal cancer (CRC) and renal carcinoma (RCC).

At the planned interim analysis, 15 patients with EGFR mutant NSCLC and a median of 2 prior lines of therapy had been treated with a median of 11 doses of AFM24. As of the cut-off date, the data showed clinical activity and signals of anti-tumor activity in 7 out of 15 heavily pre-treated patients, including two confirmed partial responses and five patients with stable disease (SD) resulting in an objective response rate of 13% and a disease control rate of 47%. All patients with stable disease were progression free for at least 3.5 months, with one patient exhibiting ongoing SD for more than 8 months. A reduction in tumor burden was observed in five of 13 patients (38%) with available baseline and subsequent tumor assessments based on RECIST criteria. All patients showed a well-managed safety profile with the majority exhibiting mild-to-moderate treatment-related adverse events in-line with previous findings, highlighting the well-managed safety profile that makes AFM24 a candidate for combination approaches. One Grade 5 (pneumonitis) adverse event was reported in a patient with progressive disease and multiple comorbidities; however, since relation to AFM24 could not be ruled out it is deemed treatment related. Although the formal continuation criteria for the cohort were not met, these data provide proof of concept that targeting NK cells can induce remission in patients with especially hard-to-treat solid tumors.

"We believe that AFM24 can be an important addition to the treatment armamentarium for addressing EGFR mutant tumors as the early anti-tumor effects support further evaluation in a combination setting with the goal of achieving meaningful patient benefit. That is why we are adding an EGFR mutant NSCLC cohort to our ongoing phase 1/2 study in combination with Roche’s PD-L1 checkpoint inhibitor atezolizumab," said Dr. Andreas Harstrick, Chief Medical Officer at Affimed. "Our broad AFM24 program aimed at identifying the right therapeutic settings and indications, and we believe that the data generated to date allow us to build the right path forward to maximize patient benefit."

STRATEGIC DEVELOPMENT OF AFM24
Based on the totality of the data accumulated for AFM24 to date, Affimed will focus its near-term development efforts on advancing AFM24 in combination with checkpoint inhibitors as part of its ongoing AFM24-102 study to further investigate the synergies between AFM24 and atezolizumab. Enrollment in the AFM24-101 monotherapy study will be concluded. An expansion cohort investigating EGFR mutant NSCLC will be added to AFM24-102 based on the encouraging signals observed in AFM24-101. Enrollment for the AFM24-102 combination study is ongoing with early encouraging case studies from the dose escalation supporting the hypothesis of combining innate and adaptive immunotherapy approaches in EGFR-positive solid tumors. An initial data update from the dose escalation and expansion part of the study is expected in the second half of 2023.

AFM24 is also currently being investigated in combination with an autologous NK cell product together with NKGen Biotech. The dose escalation part of this study is ongoing and initial data are expected to be available in H2 2023. Affimed and NKGen have mutually decided to discontinue the study. In line with Affimed’s NK cell combination experience for AFM13, the Company will evaluate the best options to advance this project with an allogeneic off-the-shelf NK cell product which the Company expects to be better suited for combination with AFM24 in a highly advanced patient population.

The Company will provide further details, including data from all three AFM24 monotherapy cohorts, and guidance on the clinical development plan for AFM24 in a conference call and webcast scheduled today.

Conference Call and Webcast Information Affimed will host a conference call and webcast on June 3, 2023, at 6:00 p.m. CDT / 7:00 p.m. EDT to review the monotherapy data and provide a strategic update on the AFM24 program going forward.

The conference call will be available via phone and webcast. The live audio webcast of the call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source To access the call by phone, please use link: https://register.vevent.com/register/BIca5147f060da49d5963a0b00a7bc8a66 and you will be provided with dial-in details and a pin number.

Note: To avoid delays, we encourage participants to dial into the conference call 15 minutes ahead of the scheduled start time. A replay of the webcast will be accessible at the same link for 30 days following the call.

More details about the programs for the ASCO (Free ASCO Whitepaper) Annual Meetings are available online at www.asco.org

About AFM24
AFM24 is a tetravalent, bispecific innate cell engager (ICE) that activates the innate immune system by binding to CD16A on innate immune cells and EGFR, a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

Affimed is evaluating AFM24 as monotherapy and in combinations with other cancer treatments in patients with advanced EGFR-expressing solid malignancies whose disease has progressed after treatment with previous anticancer therapies.

AFM24-101, a monotherapy, first-in-human phase 1/2a open-label, is a non-randomized, multi-center, multiple ascending dose escalation and expansion study. Additional details may be found at www.clinicaltrials.gov using the identifier NCT04259450.

AFM24 is also being evaluated in a phase 1/2a study in combination with Roche’s PD-L1 checkpoint inhibitor atezolizumab (AFM24-102, NCT05109442).

Furthermore, Affimed and NKGen Biotech are investigating AFM24 in combination with NKGen Biotech’s NK cell SNK01 in a phase 1/2a study (AFM24-103, NCT05099549).

On June 3, 2023 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel class of tumor-directed oncolytic immunotherapies, reported updated data from the first 75 patients in the anti-PD1 failed melanoma cohort of the IGNYTE clinical trial along with data from the ongoing Phase 1 trial of RP2 combined with nivolumab in patients with uveal melanoma are being presented at the ASCO (Free ASCO Whitepaper) annual meeting (Press release, Replimune, JUN 3, 2023, View Source [SID1234632425]). The anti-PD1 failed melanoma cohort of the IGNYTE clinical trial evaluating RP1 (vusolimogene oderparepvec) in combination with nivolumab is registration-directed.

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"We are excited to share further data from these ongoing clinical trials evaluating our novel tumor-directed oncolytic immunotherapies, RP1 and RP2," said Robert Coffin, President and Chief Research & Development Officer of Replimune. "The IGNYTE data demonstrate RP1 combined with nivolumab provides deep and durable responses with clinically meaningful rates of response in each of the anti-PD1 failed settings enrolled, and further highlights the potent systemic activity in tumors which have not been injected with RP1. These data indicate that RP1 has the potential to become a valuable new treatment option for melanoma patients following progression on anti-PD1 therapy, where treatment options are currently limited. Additionally, the data from RP2 in combination with nivolumab in uveal melanoma demonstrates a promising signal in a challenging tumor type that predominantly metastasizes to the liver, which could unlock additional opportunities for our oncolytic immunotherapies."

Updated Data from the IGNYTE Clinical Trial Cohort Evaluating RP1 Combined with Nivolumab in anti-PD1 Failed Melanoma

IGNYTE is Replimune’s multi-cohort clinical trial evaluating RP1 combined with nivolumab in multiple tumor type specific cohorts. The anti-PD1 failed melanoma cohort is registration-directed and completed enrollment earlier in the year with 141 patients enrolled. These updated data include the first 75 patients from the anti-PD1 failed melanoma cohort combined with the 16 anti-PD1 failed melanoma patients from the prior all comers 30 patient melanoma cohort (n=91 in total). The IGNYTE clinical trial is being conducted under a collaboration and supply agreement with Bristol Myers Squibb.

With a median follow up of 75.9 weeks, the updated data show an overall objective response rate (ORR) of 37.4% (37.5% in the 16 patients from the prior cohort, 37.3% in the 75 patients from the new cohort), with an ORR of at least 28.3% in all subgroups analyzed, including in patients:
Having failed anti-CTLA-4 therapy as well as anti-PD1 therapy (34.4% ORR, n=32)
With Stage IVM1b/c disease (28.3% ORR, n=46)
Who progressed while on prior adjuvant anti-PD1 therapy (50% ORR, n=32); patients who progressed after stopping adjuvant therapy were not eligible for the trial
With both primary refractory (36.0% ORR, n=50) and secondary refractory (42.1% ORR, n=38) disease
The data show systemic activity, with both injected and in un-injected lesions responding with similar durability and kinetics, including in un-injected visceral disease.
From when last reported in December 2022, all responding patients remain in response, further highlighting the duration of benefit; 85 percent of responses are ongoing with 71 percent of responders out over one year from starting therapy.
Patients with up to >20cm of total disease responded, including patients with up to >10cm of uninjected disease.
Updated analyses demonstrate activity in patients with PD-L1 negative tumors as well as those whose tumors were PD-L1 positive and with both BRAF wild type and BRAF mutant disease.
Analysis of PFS and ORR for the population as a whole and broken down by prognostic and other factors was also provided. This demonstrated that PFS and OS are most strongly impacted by response to RP1 combined with nivolumab, but not impacted by whether all lesions were or were not injected with RP1. Other factors assessed (disease stage, prior treatment setting [adjuvant vs not adjuvant prior anti-PD1], prior anti-CTLA-4 or no prior anti-CTLA-4) had only a more modest impact on progression-free survival (PFS) and overall survival (OS).
RP1 continues to be generally well tolerated with safety data showing predominantly ‘on target’ flu-like Grade 1-2 side effects indicative of systemic immune activation. Grade 3 treatment related events were rarely seen in the 91-patient group, with a range of Grade 3 events in one patient each, and two Grade 3 events of fatigue. There were two Grade 4 treatment related events (elevated lipase, and cytokine release syndrome) and no treatment related Grade 5 events.
The ORR data for this snapshot was investigator assessed. The primary endpoint is ORR for all patients in the cohort which will be assessed by central review.

The poster presented at ASCO (Free ASCO Whitepaper) can be found on our website under Presentations.

Updated Data from RP2 Combined with Nivolumab in Uveal Melanoma

RP2 leverages the Company’s platform to express an anti-CTLA-4 antibody, in addition to the GALV-GP R- and GM-CSF expressed by RP1. Data in uveal melanoma patients from the Phase 1 clinical trial evaluating RP2 in combination with nivolumab was presented. The Company believes the data in uveal melanoma provides a proxy for the potential treatment of a range of intractable tumor types that metastasize to the liver. This trial is being conducted under a collaboration and supply agreement with Bristol Myers Squibb.

Seventeen patients have been treated with RP2 as monotherapy (N=3) or in combination with nivolumab (N=14) to date, with enrollment of uveal melanoma patients into this clinical trial now being complete.
Four of the 14 patients which are so far evaluable have responded to treatment (28.6%), including metastatic tumors in the liver and bone. The final three of 17 patients remain on treatment, but currently have insufficient follow-up data to determine response outcome as of the cut-off date. Three of the four responses are ongoing at 9, 12 and 21 months, including for patients with liver and bone metastases, with the fourth patient having progressed at 15 months.
The safety profile as monotherapy and in combination with nivolumab was generally well tolerated with no additive adverse events observed.
The poster presented at ASCO (Free ASCO Whitepaper) can be found on our website under Presentations.
Additional Abstracts Being Presented at ASCO (Free ASCO Whitepaper)

Three additional trial-in-progress abstracts were presented at ASCO (Free ASCO Whitepaper) outlining Phase 2 development plans for RP2 and RP3.

A Phase 2, open-label, multicenter study investigating efficacy and safety of RP3 oncolytic immunotherapy combined with other therapies in patients with locoregionally advanced or recurrent squamous cell carcinoma of the head and neck (SCCHN)

A two-cohort clinical trial will be conducted, with the first cohort of 100 patients with locally advanced disease being randomized to receive either standard of care (SOC) chemotherapy combined with radiation or RP3 combined with chemotherapy and radiation followed by adjuvant nivolumab therapy. The second, signal finding cohort, will enroll 30 patients with recurrent or metastatic SCCHN with low PDL1 levels (CPS<20) who will be treated with chemotherapy, nivolumab and RP3.

An open-label clinical trial of RP2 and RP3 oncolytic immunotherapy in combination with atezolizumab and bevacizumab for the treatment of patients with advanced colorectal carcinoma (CRC)

Two signal finding cohorts of 30 patients each will be enrolled in collaboration with Roche. The first cohort will enroll patients to be treated with atezolizumab combined with bevacizumab and RP2 and the second cohort with atezolizumab and bevacizumab and RP3. The Company believes that data with both RP2 and RP3 in CRC will allow the comparative efficacy of RP2 and RP3 to be evaluated in a particularly difficult to treat patient population.

An open-label, multicenter study investigating RP3 oncolytic immunotherapy in combination with first- or second-line systemic atezolizumab and bevacizumab therapy in patients with locally advanced unresectable or metastatic hepatocellular carcinoma (HCC)

Two signal finding cohorts of 30 patients each will be enrolled in collaboration with Roche. The first cohort will enroll 1L HCC patients treated with SOC atezolizumab combined with bevacizumab and RP3, and the second cohort will enroll HCC patients who have progressed on 1L immunotherapy (including atezolizumab/bevacizumab) and will be treated with atezolizumab combined with bevacizumab and RP3.
These clinical trials are currently in the trial set up phase and are expected to initiate around mid-year.

About IGNYTE
IGNYTE (NCT03767348) is Replimune’s multi-cohort Phase 1/2 trial of RP1 plus nivolumab. There are 3 tumor specific cohorts currently enrolling in this clinical trial including a 125-patient cohort in anti-PD1 failed cutaneous melanoma with registrational intent. This cohort was initiated after completing enrollment in a prior Phase 2 cohort in the same clinical trial of approximately 30 patients with melanoma. The additional cohorts include non-melanoma skin cancers which includes both naïve and anti-PD1 failed CSCC. This trial is being conducted under a collaboration and supply agreement with Bristol Myers Squibb.

About RP1
RP1 (vusolimogene oderparepvec) is Replimune’s lead product candidate and is based on a proprietary new strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.

About RP2 & RP3
RP2 and RP3 are derivatives of RP1 that express additional immune-activating proteins. RP2 expresses an anti-CTLA-4 antibody-like molecule and RP3 additionally expresses the immune co-stimulatory pathway activating proteins CD40L and 4-1BBL, but does not express GM-CSF. RP2 and RP3 are intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic immune-based efficacy on tumors and limiting off-target toxicity.